Sample records for nafld activity score

  1. A comparison of FibroMeter™ NAFLD Score, NAFLD fibrosis score, and transient elastography as noninvasive diagnostic tools for hepatic fibrosis in patients with biopsy-proven non-alcoholic fatty liver disease.

    PubMed

    Aykut, Umut Emre; Akyuz, Umit; Yesil, Atakan; Eren, Fatih; Gerin, Fatma; Ergelen, Rabia; Celikel, Cigdem Ataizi; Yilmaz, Yusuf

    2014-11-01

    Noninvasive markers that purport to distinguish patients with non-alcoholic fatty liver disease (NAFLD) with fibrosis from those without must be evaluated rigorously for their classification accuracy. Herein, we seek to compare the diagnostic performances of three different noninvasive methods (FibroMeter™ NAFLD score, NAFLD Fibrosis score (NFSA), and Transient Elastrography [TE]) for the detection of liver fibrosis in NAFLD patients. A total of 88 patients with biopsy-proven NAFLD were included. The Kleiner system was used for grading fibrosis in liver biopsies. The FibroMeter™ NAFLD score was determined using a proprietary algorithm (regression score). The NFSA score was calculated based on age, hyperglycemia, body mass index, platelets, albumin and serum aminotransferase levels. TE was performed using the Fibroscan apparatus. The sensitivities/specificities for the FibroMeter™ NAFLD score, NFSA, and TE for the diagnosis of significant fibrosis (F2 + F3 + F4 fibrosis) were 38.6%/86.4%, 52.3%/88.6%, and 75.0%/93.2%, respectively. The areas under the receiver operating characteristic curves of TE were significantly higher than those of both the FibroMeter™ NAFLD score and NFSA. No significant differences were found between the FibroMeter™ NAFLD score and NFSA for the detection of significant and severe fibrosis, although the diagnostic performance of the FibroMeter™ NAFLD score was higher than that of the NFSA score for cirrhosis. In summary, TE showed the best diagnostic performance for the noninvasive assessment of liver fibrosis in NAFLD patients. The diagnostic performances of the FibroMeter™ NAFLD score and NFSA did not differ significantly for the detection of both significant and severe fibrosis.

  2. NAFLD fibrosis score: a prognostic predictor for mortality and liver complications among NAFLD patients.

    PubMed

    Treeprasertsuk, Sombat; Björnsson, Einar; Enders, Felicity; Suwanwalaikorn, Sompongse; Lindor, Keith D

    2013-02-28

    To study whether the severity of liver fibrosis estimated by the nonalcoholic fatty liver disease (NAFLD) fibrosis score can predict all-cause mortality, cardiac complications, and/or liver complications of patients with NAFLD over long-term follow-up. A cohort of well-characterized patients with NAFLD diagnosed during the period of 1980-2000 was identified through the Rochester Epidemiology Project. The NAFLD fibrosis score (NFS) was used to separate NAFLD patients with and without advanced liver fibrosis. We used the NFS score to classify the probability of fibrosis as < -1.5 for low probability, > -1.5 to < 0.67 for intermediate probability, and > 0.67 for high probability. Primary endpoints included all-cause death and cardiovascular- and/or liver-related mortality. From the 479 patients with NAFLD assessed, 302 patients (63%) greater than 18 years old were included. All patients were followed, and medical charts were reviewed until August 31, 2009 or the date when the first primary endpoint occurred. By using a standardized case record form, we recorded a detailed history and physical examination and the use of statins and metformin during the follow-up period. A total of 302/479 (63%) NAFLD patients (mean age: 47 ± 13 year) were included with a follow-up period of 12.0 ± 3.9 year. A low probability of advanced fibrosis (NFS < -1.5 at baseline) was found in 181 patients (60%), while an intermediate or high probability of advanced fibrosis (NSF > -1.5) was found in 121 patients (40%). At the end of the follow-up period, 55 patients (18%) developed primary endpoints. A total of 39 patients (13%) died during the follow-up. The leading causes of death were non-hepatic malignancy (n = 13/39; 33.3%), coronary heart disease (CHD) (n = 8/39; 20.5%), and liver-related mortality (n = 5/39; 12.8%). Thirty patients had new-onset CHD, whereas 8 of 30 patients (27%) died from CHD-related causes during the follow-up. In a multivariate analysis, a higher NFS at baseline and

  3. Clinical risk scoring for predicting non-alcoholic fatty liver disease in metabolic syndrome patients (NAFLD-MS score).

    PubMed

    Saokaew, Surasak; Kanchanasuwan, Shada; Apisarnthanarak, Piyaporn; Charoensak, Aphinya; Charatcharoenwitthaya, Phunchai; Phisalprapa, Pochamana; Chaiyakunapruk, Nathorn

    2017-10-01

    Non-alcoholic fatty liver disease (NAFLD) can progress from simple steatosis to hepatocellular carcinoma. None of tools have been developed specifically for high-risk patients. This study aimed to develop a simple risk scoring to predict NAFLD in patients with metabolic syndrome (MetS). A total of 509 patients with MetS were recruited. All were diagnosed by clinicians with ultrasonography-confirmed whether they were patients with NAFLD. Patients were randomly divided into derivation (n=400) and validation (n=109) cohort. To develop the risk score, clinical risk indicators measured at the time of recruitment were built by logistic regression. Regression coefficients were transformed into item scores and added up to a total score. A risk scoring scheme was developed from clinical predictors: BMI ≥25, AST/ALT ≥1, ALT ≥40, type 2 diabetes mellitus and central obesity. The scoring scheme was applied in validation cohort to test the performance. The scheme explained, by area under the receiver operating characteristic curve (AuROC), 76.8% of being NAFLD with good calibration (Hosmer-Lemeshow χ 2 =4.35; P=.629). The positive likelihood ratio of NAFLD in patients with low risk (scores below 3) and high risk (scores 5 and over) were 2.32 (95% CI: 1.90-2.82) and 7.77 (95% CI: 2.47-24.47) respectively. When applied in validation cohort, the score showed good performance with AuROC 76.7%, and illustrated 84%, and 100% certainty in low- and high-risk groups respectively. A simple and non-invasive scoring scheme of five predictors provides good prediction indices for NAFLD in MetS patients. This scheme may help clinicians in order to take further appropriate action. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Hepatic artery resistive index (HARI) and non-alcoholic fatty liver disease (NAFLD) fibrosis score in NAFLD patients: cut-off suggestive of non-alcoholic steatohepatitis (NASH) evolution.

    PubMed

    Tana, Claudio; Tana, Marco; Rossi, Stefano; Silingardi, Mauro; Schiavone, Cosima

    2016-09-01

    Conventional ultrasound (US) is reliable to reveal the presence of non-alcoholic fatty liver disease (NAFLD), but it is neither sensitive nor specific to reveal fibrosis clues, except in advanced stages where signs of cirrhosis are evident. NALFD fibrosis score is a non-invasive parameter that predicts well the presence of significant fibrosis, but correlations with US parameters are lacking. The aim of this study was, therefore, to compare resistive index of hepatic artery (HARI) of NAFLD patients with different severity degrees of diffuse fatty liver disease vs HARI of controls, and to compare HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls. This was a spontaneous, no-profit observational study conducted in our US department between December 2013 and July 2014. Patients with NAFLD with different severity of disease and healthy controls were included. Echogenicity and size of liver and spleen, maximum portal vein velocity, RI, peak systolic velocity (PSV), and end diastolic velocity (EDV) of splenic artery, PSV, EDV, and RI of hepatic artery, and NAFLD fibrosis score were acquired and compared between groups. HARI was significantly lower in NAFLD patients than controls (p < 0.0001). A significant difference was also found between the groups of NAFLD severity (p < 0.0001). There was also a difference between HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls (p < 0.0001) with a positive correlation between HARI and NAFLD fibrosis score. Conventional Doppler US can be helpful to detect NAFLD patients with the risk of fibrous tissue accumulation. HARI tends to exceed the range of controls for patients with NAFLD fibrosis score greater than 0.675. The detection of HARI greater than 0.9 in NAFLD patients, regardless of the US degree of severity of steatosis, might suggest the execution of biopsy to predict the risk of progression to steatohepatitis and fibrous tissue accumulation. Low values of HARI may

  5. Non-alcoholic fatty liver disease (NAFLD) fibrosis score predicts 6.6-year overall mortality of Chinese patients with NAFLD.

    PubMed

    Xun, Yun-Hao; Guo, Jian-Chun; Lou, Guo-Qiang; Jiang, Yan-Ming; Zhuang, Zhen-Jie; Zhu, Meng-Fei; Luo, Yan; Ma, Xiao-Jie; Liu, Jing; Bian, Dong-Xue; Shi, Jun-Ping

    2014-09-01

    The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has emerged as a useful predictor of long-term outcome in NAFLD patients. We evaluated the predictive performance of the NFS for overall mortality in a Chinese population with NAFLD. All NAFLD patients diagnosed ultrasonographically at Xixi Hospital of Hangzhou between 1996 and 2011 were retrospectively recruited to the study. Outcome was determined by interview and causes of death were confirmed by medical records. The area under the receiver operating characteristic curve (AUCROC ) was used to determine the predictive accuracy of the NFS, BARD (body mass index, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, diabetes) score, FIB-4 index and the AST/platelet ratio index (APRI) for mortality. Data from a total of 180 eligible patients (median age 39 years; 96 men) were analysed, with 12 deaths over a median follow-up period of 6.6 years (range 0.5-14.8 years). Using Cox model analysis, the NFS as a continuous variable was identified as the only predictor for all-cause mortality (hazard ratio 2.743, 95% confidence interval (CI) 1.670-4.504). The NFS yielded the highest AUCROC of 0.828 (95% CI 0.728-0.928, P < 0.05), followed by the FIB-4 index, APRI and BARD score (AUCROC 0.806 (P < 0.05), 0.732 (P < 0.05) and 0.632, respectively). The data indicated that the NFS is a useful predictor of 6.6-year all-cause mortality for Chinese patients with NAFLD. © 2014 Wiley Publishing Asia Pty Ltd.

  6. Treatment of NAFLD with diet, physical activity and exercise.

    PubMed

    Romero-Gómez, Manuel; Zelber-Sagi, Shira; Trenell, Michael

    2017-10-01

    Lifestyle intervention can be effective when treating non-alcoholic fatty liver diseases (NAFLD) patients. Weight loss decreases cardiovascular and diabetes risk and can also regress liver disease. Weight reductions of ⩾10% can induce a near universal non-alcoholic steatohepatitis resolution and fibrosis improvement by at least one stage. However, modest weight loss (>5%) can also produce important benefits on the components of the NAFLD activity score (NAS). Additionally, we need to explore the role of total calories and type of weight loss diet, micro- and macronutrients, evidence-based benefits of physical activity and exercise and finally support these modifications through established behavioural change models and techniques for long-term maintenance of lifestyle modifications. Following a Mediterranean diet can reduce liver fat even without weight loss and is the most recommended dietary pattern for NAFLD. The Mediterranean diet is characterised by reduced carbohydrate intake, especially sugars and refined carbohydrates (40% of the calories vs. 50-60% in a typical low fat diet), and increased monounsaturated and omega-3 fatty acid intake (40% of the calories as fat vs. up-to 30% in a typical low fat diet). Both TV sitting (a reliable marker of overall sedentary behaviour) and physical activity are associated with cardio-metabolic health, NAFLD and overall mortality. A 'triple hit behavioural phenotype' of: i) sedentary behaviour, ii) low physical activity, and iii) poor diet have been defined. Clinical evidence strongly supports the role of lifestyle modification as a primary therapy for the management of NAFLD and NASH. This should be accompanied by the implementation of strategies to avoid relapse and weight regain. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  7. Cost-Effectiveness Analysis: Risk Stratification of Nonalcoholic Fatty Liver Disease (NAFLD) by the Primary Care Physician Using the NAFLD Fibrosis Score.

    PubMed

    Tapper, Elliot B; Hunink, M G Myriam; Afdhal, Nezam H; Lai, Michelle; Sengupta, Neil

    2016-01-01

    The complications of Nonalcoholic Fatty Liver Disease (NAFLD) are dependent on the presence of advanced fibrosis. Given the high prevalence of NAFLD in the US, the optimal evaluation of NAFLD likely involves triage by a primary care physician (PCP) with advanced disease managed by gastroenterologists. We compared the cost-effectiveness of fibrosis risk-assessment strategies in a cohort of 10,000 simulated American patients with NAFLD performed in either PCP or referral clinics using a decision analytical microsimulation state-transition model. The strategies included use of vibration-controlled transient elastography (VCTE), the NAFLD fibrosis score (NFS), combination testing with NFS and VCTE, and liver biopsy (usual care by a specialist only). NFS and VCTE performance was obtained from a prospective cohort of 164 patients with NAFLD. Outcomes included cost per quality adjusted life year (QALY) and correct classification of fibrosis. Risk-stratification by the PCP using the NFS alone costs $5,985 per QALY while usual care costs $7,229/QALY. In the microsimulation, at a willingness-to-pay threshold of $100,000, the NFS alone in PCP clinic was the most cost-effective strategy in 94.2% of samples, followed by combination NFS/VCTE in the PCP clinic (5.6%) and usual care in 0.2%. The NFS based strategies yield the best biopsy-correct classification ratios (3.5) while the NFS/VCTE and usual care strategies yield more correct-classifications of advanced fibrosis at the cost of 3 and 37 additional biopsies per classification. Risk-stratification of patients with NAFLD primary care clinic is a cost-effective strategy that should be formally explored in clinical practice.

  8. Portal inflammation during NAFLD is frequent and associated with the early phases of putative hepatic progenitor cell activation.

    PubMed

    Carotti, Simone; Vespasiani-Gentilucci, Umberto; Perrone, Giuseppe; Picardi, Antonio; Morini, Sergio

    2015-11-01

    We investigated whether portal tract inflammation observed in non-alcoholic fatty liver disease (NAFLD) is associated with hepatic progenitor cell compartment activation, as thoroughly evaluated with different markers of the staminal lineage. Fifty-two patients with NAFLD were studied. NAFLD activity score, fibrosis and portal inflammation were histologically evaluated. Putative hepatic progenitor cells, intermediate hepatobiliary cells and bile ductules/interlobular bile ducts were evaluated by immunohistochemistry for cytokeratin (CK)-7, CK-19 and epithelial cell adhesion molecule (EpCAM), and a hepatic progenitor cell compartment score was derived. Hepatic stellate cell and myofibroblast activity was determined by immunohistochemistry for α-smooth muscle actin. Portal inflammation was absent in a minority of patients, mild in 40% of cases and more than mild in about half of patients, showing a strong correlation with fibrosis (r=0.76, p<0.001). Portal inflammation correlated with CK-7-counted putative hepatic progenitor cells (r=0.48, p<0.001), intermediate hepatobiliary cells (r=0.6, p<0.001) and bile ductules/interlobular bile ducts (r=0.6, p<0.001), and with the activity of myofibroblasts (r=0.5, p<0.001). Correlations were confirmed when elements were counted by immunostaining for CK-19 and EpCAM. Lobular inflammation, ballooning, myofibroblast activity and hepatic progenitor cell compartment activation were associated with portal inflammation by univariate analysis. In the multivariate model, the only variable independently associated with portal inflammation was hepatic progenitor cell compartment activation (OR 3.7, 95% CI 1.1 to 12.6). Portal inflammation is frequent during NAFLD and strongly associated with activation of putative hepatic progenitor cells since the first steps of their differentiation, portal myofibroblast activity and fibrosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  9. Echocardiography and NAFLD (non-alcoholic fatty liver disease).

    PubMed

    Trovato, Francesca M; Martines, Giuseppe F; Catalano, Daniela; Musumeci, Giuseppe; Pirri, Clara; Trovato, Guglielmo M

    2016-10-15

    Non-alcoholic-fatty-liver-disease (NAFLD) is associated with atherosclerosis, increased cardiovascular risks and mortality. We investigated if, independently of insulin resistance, diet, physical activity and obesity, fatty liver involvement has any relationship with echocardiographic measurements in NAFLD. 660 NAFLD and 791 non-NAFLD subjects, referred to the same out-patients medical unit for lifestyle-nutritional prescription, were studied. Congestive heart failure, myocardial infarction, malignancies, diabetes mellitus, extreme obesity, underweight-bad-nourished subjects and renal insufficiency were exclusion criteria. Liver steatosis was assessed by Ultrasound-Bright-Liver-Score (BLS), left ventricular ejection fraction (LVEF), trans-mitral E/A doppler ratio (diastolic relaxation) and left ventricular myocardial mass (LVMM/m(2)) by echocardiography. Doppler Renal artery Resistive Index (RRI), insulin resistance (HOMA) and lifestyle profile were also included in the clinical assessment. LVMM/m(2) is significantly greater in NAFLD, 101.62±34.48 vs. 88.22±25.61, p<0.0001 both in men and in women. Ejection fraction is slightly smaller only in men with NAFLD; no significant difference was observed for the E/A ratio. BMI (30.42±5.49 vs. 24.87±3.81; p<0.0001) and HOMA (2.90±1.70 vs. 1.85±1.25; p: 0.0001) were significantly greater in NAFLD patients. By Multiple-Linear-Regression, NAFLD and unhealthy dietary profile are associated also in lean non-diabetic subjects with lower systolic function, independently of BMI, dietary profile, physical activity, RRI and insulin resistance. NAFLD may be a meaningful early clue suggestive of diminishing heart function, with similar determining factors. NAFLD is amenable to management and improvement by lifestyle change counseling, addressing a dual target: reducing fatty liver, which is easily monitored by ultrasound, and, independently, maintaining a normal heart function. Copyright © 2016 Elsevier Ireland Ltd. All rights

  10. Cost-Effective Evaluation of Nonalcoholic Fatty Liver Disease With NAFLD Fibrosis Score and Vibration Controlled Transient Elastography.

    PubMed

    Tapper, Elliot B; Sengupta, Neil; Hunink, M G Myriam; Afdhal, Nezam H; Lai, Michelle

    2015-09-01

    The risk of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is traditionally assessed with a liver biopsy, which is both costly and associated with adverse events. We sought to compare the cost-effectiveness of four different strategies to assess fibrosis risk in patients with NAFLD: vibration controlled transient elastography (VCTE), the NAFLD fibrosis score (NFS), combination testing with NFS and VCTE, and liver biopsy (usual care). We developed a probabilistic decision analytical microsimulation state-transition model wherein we simulated a cohort of 10,000 50-year-old Americans with NAFLD undergoing evaluation by a gastroenterologist. VCTE performance was obtained from a prospective cohort of 144 patients with NAFLD. Both the NFS alone and the NFS/VCTE strategies were cost effective at $5,795 and $5,768 per quality-adjusted life years (QALY), respectively. In the microsimulation, the NFS alone and NFS/VCTE strategies were the most cost-effective (dominant) in 66.8 and 33.2% of samples given a willingness-to-pay threshold of $100,000 per QALY. In a sensitivity analysis, the minimum cost per liver biopsy at which the NFS is cost saving is $339 and the maximum cost per VCTE exam at which the NFS/VCTE strategy remains cost saving is $1,593. The expected value of further research on this topic is $526 million. Non-invasive risk stratification with both the NFS alone and the NFS/VCTE are cost-effective strategies for the evaluation and management of patients with NAFLD presenting to a gastroenterologist. Further research is needed to better define the natural history of NAFLD and the effect of novel treatments on decision making.

  11. Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    PubMed

    Goulart, Alessandra Carvalho; Oliveira, Ilka Regina Souza de; Alencar, Airlane Pereira; Santos, Maira Solange Camara dos; Santos, Itamar Souza; Martines, Brenda Margatho Ramos; Meireles, Danilo Peron; Martines, João Augusto dos Santos; Misciagna, Giovanni; Benseñor, Isabela Martins; Lotufo, Paulo Andrade

    2015-01-01

    Noninvasive strategies for evaluating non-alcoholic fatty liver disease (NAFLD) have been investigated over the last few decades. Our aim was to evaluate the diagnostic accuracy of a new hepatic ultrasound score for NAFLD in the ELSA-Brasil study. Diagnostic accuracy study conducted in the ELSA center, in the hospital of a public university. Among the 15,105 participants of the ELSA study who were evaluated for NAFLD, 195 individuals were included in this sub-study. Hepatic ultrasound was performed (deep beam attenuation, hepatorenal index and anteroposterior diameter of the right hepatic lobe) and compared with the hepatic steatosis findings from 64-channel high-resolution computed tomography (CT). We also evaluated two clinical indices relating to NAFLD: the fatty liver index (FLI) and the hepatic steatosis index (HSI). Among the 195 participants, the NAFLD frequency was 34.4%. High body mass index, high waist circumference, diabetes and hypertriglyceridemia were associated with high hepatic attenuation and large anteroposterior diameter of the right hepatic lobe, but not with the hepatorenal index. The hepatic ultrasound score, based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe, presented the best performance for NAFLD screening at the cutoff point ≥ 1 point; sensitivity: 85.1%; specificity: 73.4%; accuracy: 79.3%; and area under the curve (AUC 0.85; 95% confidence interval, CI: 0.78-0.91)]. FLI and HSI presented lower performance (AUC 0.76; 95% CI: 0.69-0.83) than CT. The hepatic ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe has good reproducibility and accuracy for NAFLD screening.

  12. Comparison of FIB-4 index, NAFLD fibrosis score and BARD score for prediction of advanced fibrosis in adult patients with non-alcoholic fatty liver disease: A meta-analysis study.

    PubMed

    Sun, Wenjing; Cui, Hongli; Li, Ning; Wei, Yanling; Lai, Shujie; Yang, Yang; Yin, Xinru; Chen, Dong-Feng

    2016-08-01

    Non-alcoholic fatty liver disease (NAFLD)-related advanced hepatic fibrosis is associated with liver and cardiovascular morbidity and mortality. This study aims to compare the FIB-4 index, NAFLD fibrosis score (NFS) and BARD score for prediction of advanced liver fibrosis. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver-operator curves (SROC) and Spearman's rank correlation coefficient were used to examine the accuracy of each non-invasive scoring system for predicting NAFLD-related advanced fibrosis. Four studies with 1038 adult patients were included in this meta-analysis. A total of 135 patients (13.0%) had advanced fibrosis. In the FIB-4 index group, pooled sensitivity and specificity with 95% confidence interval (CI), and the area under the ROC (AUROC) were 0.844 (0.772-0.901), 0.685 (0.654-0.716) and 0.8496 ± 0.0680, respectively, at a cut-off of 1.30. At a threshold of 3.25, the same parameters were 0.38 (0.30-0.47), 0.96 (0.95-0.98) and 0.8445 ± 0.0981. At a cut-off of -1.455, values were 0.77 (0.69-0.84), 0.70 (0.67-0.73) and 0.8355 ± 0.0667, respectively. At a 0.676 cut-off, pooled sensitivity and specificity with 95% CI were 0.27 (0.19-0.35) and 0.98 (0.96-0.98), respectively; and the AUROC was 0.647 ± 0.2208. In the BARD score group, pooled sensitivity and specificity with 95% CI were 0.74 (0.66-0.81) and 0.66 (0.63-0.69), respectively; and the AUROC was 0.7625 ± 0.0285. FIB-4 index with a 1.30 cut-off has better diagnostic accuracy than the FIB-4 index with a 3.25 cut-off, NFS and BARD score, despite showing its limited value for predicting NAFLD-related advanced fibrosis. © 2016 The Japan Society of Hepatology.

  13. A novel 2-step approach combining the NAFLD fibrosis score and liver stiffness measurement for predicting advanced fibrosis.

    PubMed

    Chan, Wah-Kheong; Nik Mustapha, Nik Raihan; Mahadeva, Sanjiv

    2015-10-01

    The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) is indeterminate in a proportion of NAFLD patients. Combining the NFS with liver stiffness measurement (LSM) may improve prediction of advanced fibrosis. We aim to evaluate the NFS and LSM in predicting advanced fibrosis in NAFLD patients. The NFS was calculated and LSM obtained for consecutive adult NAFLD patients scheduled for liver biopsy. The accuracy of predicting advanced fibrosis using either modality and in combination were assessed. An algorithm combining the NFS and LSM was developed from a training cohort and subsequently tested in a validation cohort. There were 101 and 46 patients in the training and validation cohort, respectively. In the training cohort, the percentages of misclassifications using the NFS alone, LSM alone, LSM alone (with grey zone), both tests for all patients and a 2-step approach using LSM only for patients with indeterminate and high NFS were 5.0, 28.7, 2.0, 2.0 and 4.0 %, respectively. The percentages of patients requiring liver biopsy were 30.7, 0, 36.6, 36.6 and 18.8 %, respectively. In the validation cohort, the percentages of misclassifications were 8.7, 28.3, 2.2, 2.2 and 8.7 %, respectively. The percentages of patients requiring liver biopsy were 28.3, 0, 41.3, 43.5 and 19.6 %, respectively. The novel 2-step approach further reduced the number of patients requiring a liver biopsy whilst maintaining the accuracy to predict advanced fibrosis. The combination of NFS and LSM for all patients provided no apparent advantage over using either of the tests alone.

  14. Laboratory parameter-based machine learning model for excluding non-alcoholic fatty liver disease (NAFLD) in the general population.

    PubMed

    Yip, T C-F; Ma, A J; Wong, V W-S; Tse, Y-K; Chan, H L-Y; Yuen, P-C; Wong, G L-H

    2017-08-01

    Non-alcoholic fatty liver disease (NAFLD) affects 20%-40% of the general population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Electronic medical records facilitate large-scale epidemiological studies, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases. To develop and validate a laboratory parameter-based machine learning model to detect NAFLD for the general population. We randomly divided 922 subjects from a population screening study into training and validation groups; NAFLD was diagnosed by proton-magnetic resonance spectroscopy. On the basis of machine learning from 23 routine clinical and laboratory parameters after elastic net regulation, we evaluated the logistic regression, ridge regression, AdaBoost and decision tree models. The areas under receiver-operating characteristic curve (AUROC) of models in validation group were compared. Six predictors including alanine aminotransferase, high-density lipoprotein cholesterol, triglyceride, haemoglobin A 1c , white blood cell count and the presence of hypertension were selected. The NAFLD ridge score achieved AUROC of 0.87 (95% CI 0.83-0.90) and 0.88 (0.84-0.91) in the training and validation groups respectively. Using dual cut-offs of 0.24 and 0.44, NAFLD ridge score achieved 92% (86%-96%) sensitivity and 90% (86%-93%) specificity with corresponding negative and positive predictive values of 96% (91%-98%) and 69% (59%-78%), and 87% of overall accuracy among 70% of classifiable subjects in the validation group; 30% of subjects remained indeterminate. NAFLD ridge score is a simple and robust reference comparable to existing NAFLD scores to exclude NAFLD patients in epidemiological studies. © 2017 John Wiley & Sons Ltd.

  15. Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis.

    PubMed

    Lee, Hyo Young; Jun, Dae Won; Kim, Hyun Jung; Oh, Hyunwoo; Saeed, Waqar Khalid; Ahn, Hyeongsik; Cheung, Ramsey C; Nguyen, Mindie H

    2018-03-20

    A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis. The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs). Additional references were obtained from review of bibliography of relevant articles. The quality of evidence was assessed using the grading of recommendations assessment, development and evaluation guidelines. Three RCTs (n = 98) and two NRSs (n = 101) met our study inclusion criteria (adult, NAFLD, liver biopsy). Liver biopsy was performed in all five studies, but only the three studies reported NAS. Ezetimibe significantly decreased NAS (standardized mean difference [SMD], -0.30; 95% confidence interval [CI], -0.57 to -0.03) but not hepatic steatosis in RCT (SMD, -0.1; 95% CI, -0.53 to 0.32), while the effect was significant for both NAS and intrahepatic content in NRSs (SMD, -3.0; 95% CI, -6.9 to 0.91). Ezetimibe decreased NAS without improving hepatic steatosis.

  16. Steatosis Grade is the Most Important Risk Factor for Development of Endothelial Dysfunction in NAFLD

    PubMed Central

    Sapmaz, Ferdane; Uzman, Metin; Basyigit, Sebahat; Ozkan, Selcuk; Yavuz, Bunyamin; Yeniova, Abdullah; Kefeli, Ayse; Asilturk, Zeliha; Nazligül, Yasar

    2016-01-01

    Abstract It is shown that there are strong associations between nonalcoholic fatty liver disease (NAFLD) and endothelial dysfunction. The aim of our study was to reveal whether steatosis or fibrosis score is more important in the development of endothelial dysfunction in patients with NAFLD in a prospective manner. This cross-sectional study included 266 subjects. These subjects were divided into 2 groups depending on presence of hepatosteatosis sonographically. Patients with hepatosteatosis were also divided into 3 subgroups depending on degree of steatosis: grade 1, 2, and 3. In all patients, Aspartate aminotransferase-to-Platelet Ratio Index and Fibrosis-4 (FIB4) scores were calculated. In addition, flow-mediated dilatation (FMD) measurements were recorded. There was NAFLD in 176 (66.2%) of 266 patients included. There were no significant differences in sex and age distributions between patients with NAFLD (group 1) and controls without NAFLD (group 2) (P = 0.05). Mean Aspartate aminotransferase-to-Platelet Ratio Index score was significantly higher in group 1 compared with the control group (P = 0.001), whereas no significant difference was detected regarding FIB4 scores between groups (P = 0.4). Mean FMD value was found to be significantly lower in group 1 (P = 0.008). Patients with grade 3 hepatosteatosis had significantly lower FMD values than those with grade 1 steatosis and controls (P = 0.001). In univariate and multivariate analyses in group 1, no significant difference was detected regarding mean FMD measurements (P = 0.03). Again, no significant difference was detected in mean FMD measurement between FIB4 subgroups among patients with NAFLD and the whole study group (P = 0.09). The endothelial dysfunction is associated with steatosis in patients with NAFLD. PMID:27057890

  17. Single non-invasive model to diagnose non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

    PubMed

    Otgonsuren, Munkhzul; Estep, Michael J; Hossain, Nayeem; Younossi, Elena; Frost, Spencer; Henry, Linda; Hunt, Sharon; Fang, Yun; Goodman, Zachary; Younossi, Zobair M

    2014-12-01

    Non-alcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease (NAFLD). A liver biopsy is considered the "gold standard" for diagnosing/staging NASH. Identification of NAFLD/NASH using non-invasive tools is important for intervention. The study aims were to: develop/validate the predictive performance of a non-invasive model (index of NASH [ION]); assess the performance of a recognized non-invasive model (fatty liver index [FLI]) compared with ION for NAFLD diagnosis; determine which non-invasive model (FLI, ION, or NAFLD fibrosis score [NFS]) performed best in predicting age-adjusted mortality. From the National Health and Nutrition Examination Survey III database, anthropometric, clinical, ultrasound, laboratory, and mortality data were obtained (n = 4458; n = 861 [19.3%] NAFLD by ultrasound) and used to develop the ION model, and then to compare the ION and FLI models for NAFLD diagnosis. For validation and diagnosis of NASH, liver biopsy data were used (n = 152). Age-adjusted Cox proportional hazard modeling estimated the association among the three non-invasive tests (FLI, ION, and NFS) and mortality. FLI's threshold score > 60 and ION's threshold score > 22 had similar specificity (FLI = 80% vs ION = 82%) for NAFLD diagnosis; FLI < 30 (80% sensitivity) and ION < 11 (81% sensitivity) excluded NAFLD. An ION score > 50 predicted histological NASH (92% specificity); the FLI model did not predict NASH or mortality. The ION model was best in predicting cardiovascular/diabetes-related mortality; NFS predicted overall or diabetes-related mortality. The ION model was superior in predicting NASH and mortality compared with the FLI model. Studies are needed to validate ION. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  18. Extrahepatic Diseases and NAFLD: The Triangular Relationship between NAFLD, Type 2-Diabetes and Dysbiosis.

    PubMed

    Scorletti, Eleonora; Byrne, Christopher D

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases from simple steatosis with hepatic lipid accumulation to end-stage liver disease with decompensated cirrhosis, liver failure and hepatocellular carcinoma. Recent data from the USA showed that in 2013, NAFLD was the second most frequent indication for liver transplantation behind hepatitis C. Since there are now effective treatments for hepatitis C and there is currently no licensed treatment for NAFLD, it has been predicted that over the next 10-15 years, NAFLD will replace hepatitis C as the most frequent indication for liver transplantation. Besides, increasing the risk of hepatocellular carcinoma and end-stage liver disease, it has recently become clear that NAFLD also increases risk of extrahepatic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, cardiac diseases and chronic kidney disease, to name but a few. Of each of these extrahepatic diseases, the evidence to date suggests that NAFLD is a strong risk factor for T2DM. When NAFLD occurs in combination with obesity and insulin resistance (as it frequently does), there is a marked increase in risk of incident T2DM with possible synergism occurring between liver fat accumulation, insulin resistance and obesity to further increase risk of development of T2DM. Thus, there is a reciprocal relationship between NAFLD as a risk factor for T2DM, and T2DM as a risk factor for liver disease progression in NAFLD. Moreover, recent evidence now points to the importance of perturbation of the intestinal microbiota (dysbiosis) in both T2DM and NAFLD. Consequently, there is a triangular relationship between dysbiosis and T2DM and NAFLD. This review will focus on T2DM as a key extrahepatic complication of NAFLD and will describe and discuss the triangular relationship between dysbiosis and T2DM and NAFLD and the factors and potential mechanisms underpinning this relationship. © 2016 S. Karger AG, Basel.

  19. High Dietary Sodium Intake Assessed by Estimated 24-h Urinary Sodium Excretion Is Associated with NAFLD and Hepatic Fibrosis.

    PubMed

    Huh, Ji Hye; Lee, Kyong Joo; Lim, Jung Soo; Lee, Mi Young; Park, Hong Jun; Kim, Moon Young; Kim, Jae Woo; Chung, Choon Hee; Shin, Jang Yel; Kim, Hyun-Soo; Kwon, Sang Ok; Baik, Soon Koo

    2015-01-01

    Although high sodium intake is associated with obesity and hypertension, few studies have investigated the relationship between sodium intake and non-alcoholic fatty liver disease (NAFLD). We evaluated the association between sodium intake assessed by estimated 24-h urinary sodium excretion and NAFLD in healthy Koreans. We analyzed data from 27,433 participants in the Korea National Health and Nutrition Examination Surveys (2008-2010). The total amount of sodium excretion in 24-h urine was estimated using Tanaka's equations from spot urine specimens. Subjects were defined as having NAFLD when they had high scores in previously validated NAFLD prediction models such as the hepatic steatosis index (HSI) and fatty liver index (FLI). BARD scores and FIB-4 were used to define advanced fibrosis in subjects with NAFLD. The participants were classified into three groups according to estimated 24-h urinary excretion tertiles. The prevalence of NAFLD as assessed by both FLI and HSI was significantly higher in the highest estimated 24-h urinary sodium excretion tertile group. Even after adjustment for confounding factors including body fat and hypertension, the association between higher estimated 24-h urinary sodium excretion and NAFLD remained significant (Odds ratios (OR) 1.39, 95% confidence interval (CI) 1.26-1.55, in HSI; OR 1.75, CI 1.39-2.20, in FLI, both P < 0.001). Further, subjects with hepatic fibrosis as assessed by BARD score and FIB-4 in NAFLD patients had higher estimated 24-h urinary sodium values. High sodium intake was independently associated with an increased risk of NAFLD and advanced liver fibrosis.

  20. High Dietary Sodium Intake Assessed by Estimated 24-h Urinary Sodium Excretion Is Associated with NAFLD and Hepatic Fibrosis

    PubMed Central

    Huh, Ji Hye; Lee, Kyong Joo; Lim, Jung Soo; Lee, Mi Young; Park, Hong Jun; Kim, Moon Young; Kim, Jae Woo; Chung, Choon Hee; Shin, Jang Yel; Kim, Hyun-Soo; Kwon, Sang Ok; Baik, Soon Koo

    2015-01-01

    Background Although high sodium intake is associated with obesity and hypertension, few studies have investigated the relationship between sodium intake and non-alcoholic fatty liver disease (NAFLD). We evaluated the association between sodium intake assessed by estimated 24-h urinary sodium excretion and NAFLD in healthy Koreans. Methods We analyzed data from 27,433 participants in the Korea National Health and Nutrition Examination Surveys (2008–2010). The total amount of sodium excretion in 24-h urine was estimated using Tanaka’s equations from spot urine specimens. Subjects were defined as having NAFLD when they had high scores in previously validated NAFLD prediction models such as the hepatic steatosis index (HSI) and fatty liver index (FLI). BARD scores and FIB-4 were used to define advanced fibrosis in subjects with NAFLD. Results The participants were classified into three groups according to estimated 24-h urinary excretion tertiles. The prevalence of NAFLD as assessed by both FLI and HSI was significantly higher in the highest estimated 24-h urinary sodium excretion tertile group. Even after adjustment for confounding factors including body fat and hypertension, the association between higher estimated 24-h urinary sodium excretion and NAFLD remained significant (Odds ratios (OR) 1.39, 95% confidence interval (CI) 1.26–1.55, in HSI; OR 1.75, CI 1.39–2.20, in FLI, both P < 0.001). Further, subjects with hepatic fibrosis as assessed by BARD score and FIB-4 in NAFLD patients had higher estimated 24-h urinary sodium values. Conclusions High sodium intake was independently associated with an increased risk of NAFLD and advanced liver fibrosis. PMID:26571018

  1. TRUSS exacerbates NAFLD development by promoting IκBα degradation.

    PubMed

    Yu, Chang-Jiang; Wang, Qiu-Shi; Wu, Ming-Ming; Song, Bin-Lin; Liang, Chen; Lou, Jie; Tang, Liang-Liang; Yu, Xiao-Di; Niu, Na; Yang, Xu; Zhang, Bao-Long; Qu, Yao; Liu, Yang; Dong, Zhi-Chao; Zhang, Zhi-Ren

    2018-04-27

    There is no effective treatment method for non-alcoholic fatty liver disease (NAFLD), the most common liver disease. The exact mechanism underlying the pathogenesis of NAFLD remains to be elucidated. Here, we report that tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein (TRUSS) acts as a positive regulator of NAFLD and in a variety of metabolic disorders. TRUSS expression was respectively increased in the human liver specimens with NAFLD or non-alcoholic steatohepatitis (NASH), and in the livers of high-fat diet (HFD)-induced and genetically obese (ob/ob) mice. Conditional knockout of TRUSS in hepatocytes significantly ameliorated hepatic steatosis, insulin resistance (IR), glucose intolerance, and inflammatory responses in mice after HFD challenge or in spontaneous obese mice with normal chow (NC) feeding. All these HFD-induced pathological phenotypes were exacerbated in mice overexpressing TRUSS in hepatocytes. We show that TRUSS physically interacts with IκBα and promotes the ubiquitination and degradation of IκBα, which leading to aberrant activation of NF-κB. Overexpressing IκBα S32A/S36A , a phosphorylation-resistant mutant of IκBα, in the hepatocyte-specific TRUSS overexpressing mice almost abolished HFD-induced NAFLD and metabolic disorders. Hepatocyte TRUSS promotes pathological stimuli-induced NAFLD and metabolic disorders, via activation of NF-κB by promoting ubiquitination and degradation of IκBα. Our findings may provide a novel strategy for prevention and treatment of NAFLD by targeting TRUSS. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  2. More Frequent Clinic Visits Are Associated with Improved Outcomes for Children with NAFLD

    PubMed Central

    Lam, Carol; Bandsma, Robert; Ling, Simon

    2016-01-01

    Objective. Adult data suggest that frequent monitoring of patients with nonalcoholic fatty liver disease (NAFLD) may be associated with improved outcomes. The optimal frequency of outpatient visits for the management of pediatric NAFLD remains unknown. Study Design. In this retrospective study, two cohorts of patients with NAFLD, one followed on a yearly basis and one followed on 3-month intervals, were included. Both received similar advice regarding lifestyle changes. Primary outcome was change in BMI z-scores over a year. Secondary outcomes were the change in serum transaminases and markers of metabolic dysregulation. Results. Fifty-six patients were included (28 per group). The majority (71%) were male with a mean (±SD) age of 12.2 (±2.7) years. At baseline, there were no differences in BMI z-scores (2.8 versus 2.9; p = 0.72) and ALT levels (101 versus 100 U/L; p = 0.95) between the groups (yearly versus three-month, resp.). Twelve months later, those followed on a 3-month basis demonstrated a significant decrease in BMI (net BMI z-score change = −0.06; p = 0.37), accompanied by a significant improvement in serum ALT (−25 U/L; p < 0.01) and AST (−13 U/L; p = 0.03) levels. There were no differences in fasting lipid profiles. Conclusion. Frequent clinic visits are associated with improved outcomes in pediatric NAFLD. PMID:28058253

  3. Quantitative Imaging Biomarkers of NAFLD

    PubMed Central

    Kinner, Sonja; Reeder, Scott B.

    2016-01-01

    Conventional imaging modalities, including ultrasonography (US), computed tomography (CT), and magnetic resonance (MR), play an important role in the diagnosis and management of patients with nonalcoholic fatty liver disease (NAFLD) by allowing noninvasive diagnosis of hepatic steatosis. However, conventional imaging modalities are limited as biomarkers of NAFLD for various reasons. Multi-parametric quantitative MRI techniques overcome many of the shortcomings of conventional imaging and allow comprehensive and objective evaluation of NAFLD. MRI can provide unconfounded biomarkers of hepatic fat, iron, and fibrosis in a single examination—a virtual biopsy has become a clinical reality. In this article, we will review the utility and limitation of conventional US, CT, and MR imaging for the diagnosis NAFLD. Recent advances in imaging biomarkers of NAFLD are also discussed with an emphasis in multi-parametric quantitative MRI. PMID:26848588

  4. Portal Hypertension Complications Are Frequently the First Presentation of NAFLD in Patients Undergoing Liver Transplantation Evaluation.

    PubMed

    Nagpal, Sajan Jiv Singh; Kabbany, Mohammad Nasser; Mohamad, Bashar; Lopez, Rocio; Zein, Nizar N; Alkhouri, Naim

    2016-07-01

    Nonalcoholic fatty liver disease (NAFLD) is likely to replace Hepatitis C as the leading cause of cirrhosis resulting in liver transplantation (LT) within a few years. Unfortunately, due to the lack of established guidelines for the screening of NAFLD in high-risk populations, many patients present with portal hypertension complications as their first manifestation of NAFLD require a LT evaluation. We aimed to investigate what proportion of patients who underwent LT for NAFLD-cirrhosis had knowledge of their liver disease prior to presenting with portal hypertension complications and to identify differences in clinical parameters between those with and without knowledge of preexisting NAFLD. Consecutive patients who underwent LT for NAFLD-cirrhosis at a tertiary referral center were included in the study. Demographic and clinical data at the time of the first LT evaluation visit were collected, and patient knowledge of previous NAFLD was documented. Ascites, variceal bleeding, hepatic encephalopathy, and thrombocytopenia leading to diagnosis of underlying cirrhosis were considered as the presenting symptoms of portal hypertension. A p < 0.05 was considered statistically significant. A total of 124 subjects who received LT for NAFLD-cirrhosis were included, 58 % (n = 72) were male. At the time of the first LT evaluation visit, 60 % had diabetes, the mean body mass index was 33.2 [28.6, 37.6] kg/m(2), and the mean Model for End-Stage Liver Disease (MELD) score was 14.0 [11.0, 19.0]. More importantly, 85/124 patients (68.5 %) had no knowledge of preexisting NAFLD prior to presentation with symptoms of portal hypertension. The presenting symptoms were new-onset ascites in 61 %, hepatic encephalopathy in 25 %, variceal bleeding in 18 %, thrombocytopenia in 9 %, and other in 9 % (non-exclusive). Patients with no prior knowledge of NAFLD were less likely to have a diagnosis of hypercholesterolemia (30 vs. 50 %, p = 0.035) and had a trend toward having

  5. Current Management of NAFLD

    PubMed Central

    MUNTEANU, MIHAI ALEXANDRU; NAGY, GEORGIANA ANCA; MIRCEA, PETRU ADRIAN

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. It affects about 1 billion individuals worldwide. While people with simple steatosis have no higher risk of death than the general population, people with non-alcoholic steatohepatitis are at increased risk of death compared to general population. Current management for NAFLD includes diet and lifestyle changes, management of underlying metabolic risk factors and pharmacological therapies. The objective of therapy is to prevent the complications. The problem with dietary and lifestyle interventions is that they are hard to implement. Compliance is the key. Until now, there is still no approved drug for the treatment of NAFLD. Insulin resistance is the main target of pharmacological therapy, but the question that we ask ourselves as physicians is who should receive medical treatment among NAFLD patients and for how long. PMID:27004021

  6. Nutritional Management of Insulin Resistance in Nonalcoholic Fatty Liver Disease (NAFLD)

    PubMed Central

    Conlon, Beth A.; Beasley, Jeannette M.; Aebersold, Karin; Jhangiani, Sunil S.; Wylie-Rosett, Judith

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an emerging global health concern. It is the most common form of chronic liver disease in Western countries, affecting both adults and children. NAFLD encompasses a broad spectrum of fatty liver disease, ranging from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH), and is strongly associated with obesity, insulin resistance, and dyslipidemia. First-line therapy for NAFLD includes weight loss achieved through diet and physical activity. However, there is a lack of evidenced-based dietary recommendations. The American Diabetes Association’s (ADA) recommendations that aim to reduce the risk of diabetes and cardiovascular disease may also be applicable to the NAFLD population. The objectives of this review are to: (1) provide an overview of NAFLD in the context of insulin resistance, and (2) provide a rationale for applying relevant aspects of the ADA recommendations to the nutritional management of NAFLD. PMID:24152749

  7. Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD

    PubMed Central

    Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A.; Kleiner, David; Brunt, Elizabeth M.; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James

    2015-01-01

    , international normalized ratio, and platelet count with an AUROC of 0.80 (95% CI 0.76–0.85, P < 0.001). The specificity, sensitivity, NPV, and PPV were 90.0%, 57%, 75.1%, and 80.2%, respectively, and the model correctly classified 76.6% of patients as having advanced fibrosis. Results remained consistent for both models in the validation cohort. The proposed model performed better than the NAFLD fibrosis score in detecting advanced fibrosis. CONCLUSIONS Routinely available clinical variables can be used to quantify the likelihood of NASH or advanced fibrosis in adult diabetic patients with NAFLD. The clinical models presented can be used to guide clinical decision making about referrals of patients with diabetes and NAFLD to hepatologists. PMID:25887357

  8. Differing clinical phenotype for higher alanine-aminotransferase (ALT) compared with high-risk NAFLD fibrosis score in type 2 diabetes mellitus.

    PubMed

    Williams, Kathryn H; Burns, Kharis; Twigg, Stephen M

    2018-03-01

    The impact of non-alcoholic fatty liver disease (NAFLD) presence and severity on the diabetes phenotype remains unclear. Our study aimed to explore and contrast the phenotypes associated with higher ALT and high-risk NAFLD fibrosis score (NFS) in type 2 diabetes. 324 patients with type 2 diabetes mellitus who were seen at a diabetes centre for a complications assessment with data for NFS were available for study. Data regarding co-morbidities and pathology were obtained at assessment and by file audit. Logistic regression was used to determine if there were significant relationships between pre-determined diabetes complications and co-morbidities and ALT or high-risk NFS (>0.675). Significant univariate associations with lower ALT included those of osteoporosis/osteopenia and inability to sense the monofilament. High-risk NFS was associated with arrhythmia, VPT ≥ 25 V and albuminuria. The associations of high-risk NFS with albuminuria and VPT ≥ 25 V remained after adjustment. In type 2 diabetes, the clinical phenotype of those with higher ALT is dissimilar, sometimes inverse, to those with high-risk NFS. More emphasis should be placed on liver fibrosis risk rather than on liver enzymes alone. Copyright © 2017. Published by Elsevier Inc.

  9. Gut Microbiota and Lifestyle Interventions in NAFLD

    PubMed Central

    Houghton, David; Stewart, Christopher J.; Day, Christopher P.; Trenell, Michael

    2016-01-01

    The human digestive system harbors a diverse and complex community of microorganisms that work in a symbiotic fashion with the host, contributing to metabolism, immune response and intestinal architecture. However, disruption of a stable and diverse community, termed “dysbiosis”, has been shown to have a profound impact upon health and disease. Emerging data demonstrate dysbiosis of the gut microbiota to be linked with non-alcoholic fatty liver disease (NAFLD). Although the exact mechanism(s) remain unknown, inflammation, damage to the intestinal membrane, and translocation of bacteria have all been suggested. Lifestyle intervention is undoubtedly effective at improving NAFLD, however, not all patients respond to these in the same manner. Furthermore, studies investigating the effects of lifestyle interventions on the gut microbiota in NAFLD patients are lacking. A deeper understanding of how different aspects of lifestyle (diet/nutrition/exercise) affect the host–microbiome interaction may allow for a more tailored approach to lifestyle intervention. With gut microbiota representing a key element of personalized medicine and nutrition, we review the effects of lifestyle interventions (diet and physical activity/exercise) on gut microbiota and how this impacts upon NAFLD prognosis. PMID:27023533

  10. Physical activity and sedentary behavior can modulate the effect of the PNPLA3 variant on childhood NAFLD: a case-control study in a Chinese population.

    PubMed

    Wang, Shuo; Song, Jieyun; Shang, Xiaorui; Chawla, Nitesh; Yang, Yide; Meng, Xiangrui; Wang, Haijun; Ma, Jun

    2016-12-01

    The patatin like phospholipase containing domain 3 gene (PNPLA3) rs738409 C > G polymorphism, one of the most important gene polymorphisms involved in hepatic steatosis, has been reported to interact with different nutrients and dietary patterns on Non-Alcoholic Fatty Liver Disease (NAFLD), but no studies have focused on its interaction with physical activity or sedentary behavior. Therefore, this study aims at determining whether physical activity or sedentary behavior could modulate the effect of the PNPLA3 variant on childhood NAFLD. A case-control study was conducted including 1027 Chinese children aged 7-18 years old (162 children with NAFLD and 865 children without). The anthropometric measurements, liver ultrasound examination, questionnaires and genotyping of the PNPLA3 rs738409 polymorphism were performed. Stratified analyses showed that the proportions of NAFLD increased with the G-allele number only in children who did not have enough physical activity (physical activity < 1 h/d) (OR 3.05, 95% CI 1.82-5.12, P < 0.001), and in children with a sedentary lifestyle (sedentary behavior ≥ 2 h/d) (OR 3.41, 95% CI 1.88-6.18, P < 0.001). Significant interactions on childhood NAFLD were found between the G-allele number in the PNPLA3 rs738409 polymorphism and behaviors, including physical activity (P = 0.001), sedentary behavior (P = 0.010) and the combination of physical activity and sedentary behavior (P < 0.001). This is the first study to report the interaction between the PNPLA3 rs738409 polymorphism and physical activity or sedentary behavior on NAFLD, providing new clues on the function of the PNPLA3 gene, which will also be useful for future risk assessment and personalized treatment of NAFLD.

  11. Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD.

    PubMed

    Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A; Kleiner, David; Brunt, Elizabeth M; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James; Loomba, Rohit

    2015-07-01

    an AUROC of 0.80 (95% CI 0.76-0.85, P < 0.001). The specificity, sensitivity, NPV, and PPV were 90.0%, 57%, 75.1%, and 80.2%, respectively, and the model correctly classified 76.6% of patients as having advanced fibrosis. Results remained consistent for both models in the validation cohort. The proposed model performed better than the NAFLD fibrosis score in detecting advanced fibrosis. Routinely available clinical variables can be used to quantify the likelihood of NASH or advanced fibrosis in adult diabetic patients with NAFLD. The clinical models presented can be used to guide clinical decision making about referrals of patients with diabetes and NAFLD to hepatologists. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. Activation of proteinase 3 contributes to Non-alcoholic Fatty Liver Disease (NAFLD) and insulin resistance.

    PubMed

    Toonen, Erik J M; Mirea, Andreea-Manuela; Tack, Cees J; Stienstra, Rinke; Ballak, Dov B; van Diepen, Janna A; Hijmans, Anneke; Chavakis, Triantafyllos; Dokter, Wim H; Pham, Christine T N; Netea, Mihai G; Dinarello, Charles A; Joosten, Leo A B

    2016-05-24

    Activation of inflammatory pathways is known to accompany development of obesity-induced non-alcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes. In addition to caspase-1, the neutrophil serine proteases proteinase 3, neutrophil elastase and cathepsin G are able to process the inactive pro-inflammatory mediators IL-1β and IL-18 to their bioactive forms, thereby regulating inflammatory responses. In the present study, we investigated whether proteinase 3 is involved in obesity-induced development of insulin resistance and NAFLD. We investigated the development of NAFLD and insulin resistance in mice deficient for neutrophil elastase/proteinase 3 and neutrophil elastase/cathepsin G and in wild-type mice treated with the neutrophil serine proteinase inhibitor human alpha-1 antitrypsin. Expression profiling of metabolically relevant tissues obtained from insulin resistant mice showed that expression of proteinase 3 was specifically upregulated in the liver, whereas neutrophil elastase, cathepsin G and caspase-1 were not. Neutrophil elastase/proteinase 3 deficient mice showed strongly reduced levels of lipids in the liver after fed a high fat diet. Moreover, these mice were resistant to high fat diet-induced weight gain, inflammation and insulin resistance. Injection of proteinase 3 exacerbated insulin resistance in caspase-1(-/-) mice, indicating that proteinase 3 acts independently of caspase-1. Treatment with alpha-1 antitrypsin during the last 10 days of a 16 week high fat diet reduced hepatic lipid content and decreased fasting glucose levels. We conclude that proteinase 3 is involved in NAFLD and insulin resistance and that inhibition of proteinase 3 may have therapeutic potential.

  13. Effects of Natural Products on Fructose-Induced Nonalcoholic Fatty Liver Disease (NAFLD).

    PubMed

    Chen, Qian; Wang, Tingting; Li, Jian; Wang, Sijian; Qiu, Feng; Yu, Haiyang; Zhang, Yi; Wang, Tao

    2017-01-31

    As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance. Cellular signaling research indicated that partial factors play significant roles in fructose-induced NAFLD, involving liver X receptor (LXR)α, sterol regulatory element binding protein (SREBP)-1/1c, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD), peroxisome proliferator-activated receptor α (PPARα), leptin nuclear factor-erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), c-Jun amino terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). Until now, a series of natural products have been reported as regulators of NAFLD in vivo and in vitro. This paper reviews the natural products (e.g., curcumin, resveratrol, and (-)-epicatechin) and their mechanisms of ameliorating fructose-induced NAFLD over the past years. Although, as lead compounds, natural products usually have fewer activities compared with synthesized compounds, it will shed light on studies aiming to discover new drugs for NAFLD.

  14. Comparison of blood tests for liver fibrosis specific or not to NAFLD.

    PubMed

    Calès, Paul; Lainé, Fabrice; Boursier, Jérôme; Deugnier, Yves; Moal, Valérie; Oberti, Frédéric; Hunault, Gilles; Rousselet, Marie Christine; Hubert, Isabelle; Laafi, Jihane; Ducluzeaux, Pierre Henri; Lunel, Françoise

    2009-01-01

    To compare blood tests of liver fibrosis specific for NAFLD: the FibroMeter NAFLD and the NAFLD fibrosis score (NFSA) with a non-specific test, APRI. Two hundred and thirty-five NAFLD patients with liver Metavir staging and blood markers from two independent centres were randomly assigned to a test (n=121) or a validation population (n=114). The highest accuracy--91%--for significant fibrosis was obtained with the FibroMeter whose (i) AUROC (0.943) was significantly higher than those of NFSA (0.884, p=0.008) and APRI (0.866, p<10(-3); p=0.309 vs NFSA) in the whole population, and (ii) misclassification rate (9%) was significantly lower than those of NFSA (14%, p=0.04) and APRI (16%, p=0.002) and did not vary according to centre (14 vs 7%, p=0.07), unlike those of NFSA (25 vs 9%, p=0.001) and APRI (29 vs 11%, p<10(-3)). By using thresholds of 90% predictive values, liver biopsy could have been avoided in most patients: FibroMeter: 97.4% vs NFSA: 86.8% (p<10(-3)) and APRI: 80.0% (p<10(-3)). A new classification provided three reliable diagnosis intervals: F0/1, F0/1/2, F2/3/4 with 91.4% accuracy for FibroMeter, avoiding biopsy in all patients. FibroMeter NAFLD had high performance and provided reliable diagnosis for significant fibrosis, significantly outperforming NFSA and APRI.

  15. Non-alcoholic fatty liver disease (NAFLD) - pathogenesis, classification, and effect on drug metabolizing enzymes and transporters.

    PubMed

    Cobbina, Enoch; Akhlaghi, Fatemeh

    2017-05-01

    Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5% of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a "three-hit" process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 has been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD. These factors may result in altered expression and activity of drug metabolizing enzymes (DMEs) or transporters. Existing evidence suggests that the effect of NAFLD on CYP3A4, CYP2E1 and MRP3 is more consistent across rodent and human studies. CYP3A4 activity is down-regulated in NASH whereas the activity of CYP2E1 and the efflux transporter MRP3 is up-regulated. However, it is not clear how the majority of CYPs, UGTs, SULTs and transporters are influenced by NAFLD either in vivo or in vitro. The alterations associated with NAFLD could be a potential source of drug variability in patients and could have serious implications for the safety and efficacy of xenobiotics. In this review, we summarize the effects of NAFLD on the regulation, expression and activity of major DMEs and transporters. We also discuss the potential mechanisms underlying these alterations.

  16. The Expression of PNPLA3 Polymorphism could be the Key for Severe Liver Disease in NAFLD in Hispanic Population.

    PubMed

    Martínez, Leonardo A; Larrieta, Elena; Kershenobich, David; Torre, Aldo

    Nonalcoholic fatty liver disease (NAFLD) encompasses: fatty liver (SS), steatohepatitis (NASH) with or without fibrosis and cirrhosis. Patatine-like phosphatas in domain 3 (PNPLA3; adiponutrin; SNP rs738409 C/G, M148I) shows anabolic and catabolic activities on lipid metabolism and significant association to fatty liver content; however, I148M demographics and ethnics, as its role with NAFLD have not been fully elucidated. PNPLA3 genotyping from peripheral blood DNA by polymerase chain reaction (PCR) and direct sequencing, 211 patients diagnosed with NAFLD including SS, NASH and fibrosis spectrum. Eighty nine per cent showed the G risk allele [CC: 23 (10.5%), GC: 73 (34.7%), GG 115 (54.7%)], the allele frequency was 77%, NASH (71%), SS (80%) and fibrosis (73%). GG genotype carriers showed 3.8 times (CI 95%: 3.03 - 4.79) of increased risk of steatohepatitis and 2.3 times more (CI 95%: 1.77 ~ 3.23) risk of having liver fibrosis (CC). PNPLA3 (GC, GG) conditioned higher probability of low levels of HDL cholesterol (p < 0.010), SS even in normal weight (p < 0.007), insulin resistance by HOMA (p < 0.029), NAFLD fibrosis score showed > 0.675 (p < 0.001) and altered serum alanine aminotransferase (p < 0.05). PNPLA3 expression in Hispanics could be decisive in NAFLD pathogenesis, it's highly prevalent and it's a key to condition and determine the spectrum associated, SS, NASH and fibrosis.

  17. Non-Alcoholic Fatty Liver Disease (NAFLD) - Pathogenesis, Classification, and Effect on Drug Metabolizing Enzymes and Transporters

    PubMed Central

    Cobbina, Enoch; Akhlaghi, Fatemeh

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5 % of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a ‘three-hit’ process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 have been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD. These factors may results in altered expression and activity of drug metabolizing enzymes (DMEs) or transporters. Existing evidence suggests that the effect of NAFLD on CYP3A4, CYP2E1 and MRP3 are more consistent across rodent and human studies. CYP3A4 activity is down-regulated in NASH whereas the activity of CYP2E1 and the efflux transporter MRP3 are up-regulated. However, it is not clear how the majority of CYPs, UGTs, SULTs and transporters are influenced by NAFLD either in vivo or in vitro. The alterations associated with NAFLD could be a potential source of drug variability in patients and could have serious implications for the safety and efficacy of xenobiotics. In this review, we summarize the effects of NAFLD on the regulation, expression and activity of major drug metabolizing enzymes and transporters. We also discuss the potential mechanisms underlying these alterations. PMID:28303724

  18. Nonalcoholic fatty liver disease (NAFLD) in the Veterans Administration population: development and validation of an algorithm for NAFLD using automated data.

    PubMed

    Husain, N; Blais, P; Kramer, J; Kowalkowski, M; Richardson, P; El-Serag, H B; Kanwal, F

    2014-10-01

    In practice, nonalcoholic fatty liver disease (NAFLD) is diagnosed based on elevated liver enzymes and confirmatory liver biopsy or abdominal imaging. Neither method is feasible in identifying individuals with NAFLD in a large-scale healthcare system. To develop and validate an algorithm to identify patients with NAFLD using automated data. Using the Veterans Administration Corporate Data Warehouse, we identified patients who had persistent ALT elevation (≥2 values ≥40 IU/mL ≥6 months apart) and did not have evidence of hepatitis B, hepatitis C or excessive alcohol use. We conducted a structured chart review of 450 patients classified as NAFLD and 150 patients who were classified as non-NAFLD by the database algorithm, and subsequently refined the database algorithm. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for the initial database definition of NAFLD were 78.4% (95% CI: 70.0-86.8%), 74.5% (95% CI: 68.1-80.9%), 64.1% (95% CI: 56.4-71.7%) and 85.6% (95% CI: 79.4-91.8%), respectively. Reclassifying patients as having NAFLD if they had two elevated ALTs that were at least 6 months apart but within 2 years of each other, increased the specificity and PPV of the algorithm to 92.4% (95% CI: 88.8-96.0%) and 80.8% (95% CI: 72.5-89.0%), respectively. However, the sensitivity and NPV decreased to 55.0% (95% CI: 46.1-63.9%) and 78.0% (95% CI: 72.1-83.8%), respectively. Predictive algorithms using automated data can be used to identify patients with NAFLD, determine prevalence of NAFLD at the system-wide level, and may help select a target population for future clinical studies in veterans with NAFLD. © 2014 John Wiley & Sons Ltd.

  19. The evaluation of hepatic fibrosis scores in children with nonalcoholic fatty liver disease.

    PubMed

    Mansoor, Sana; Yerian, Lisa; Kohli, Rohit; Xanthakos, Stavra; Angulo, Paul; Ling, Simon; Lopez, Rocio; Christine, Carter-Kent; Feldstein, Ariel E; Alkhouri, Naim

    2015-05-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and can progress to liver cirrhosis during childhood. Patients with more advanced fibrosis on biopsy tend to have more liver complications. Noninvasive hepatic fibrosis scores have been developed for adult patients with NAFLD; however, these scores have not been validated in children. The aim of our study was to evaluate some of these scores in assessing the presence of fibrosis in children with biopsy-proven NAFLD. Our study consisted of 92 biopsy-proven NAFLD children from five major US centers. Fibrosis was determined by an experienced pathologist (F0-4). Clinically significant fibrosis was defined as fibrosis stage ≥ 2, and advanced fibrosis was defined as F3-4. The following fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI), NAFLD fibrosis score (NFS), and FIB-4 index. ROC was performed to assess the performance of different scores for prediction of presence of any, significant, or advanced fibrosis. A p value < 0.05 was considered statistically significant. Mean age was 13.3 ± 3 years, and 33 % were females. Eleven (12 %) subjects had no fibrosis, 35 (38 %) had fibrosis score of 1, 26 (28 %) had fibrosis score of 2, and 20 (22 %) had a score of 3. APRI had a fair diagnostic accuracy for the presence of any fibrosis (AUC of 0.80) and poor diagnostic accuracy for significant or advanced fibrosis. AST/ALT, NFS, and FIB-4 index all either had poor diagnostic accuracy or failed to diagnose the presence of any, significant, or advanced fibrosis. Noninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing significant fibrosis in children with NAFLD. Our results highlight the urgent need to develop a reliable pediatric fibrosis score.

  20. Histological scoring and associated risk factors of non-alcoholic fatty liver disease.

    PubMed

    Majid, N; Ali, Z; Rahman, M R; Akhter, A; Rajib, R C; Ahmad, F; Sharmin, S; Akond, A K; Huq, N

    2013-10-01

    Non alcoholic steatohepatitis is a hepatic disorder with histological features of alcohol induced liver disease that occurs in individual who do not consume significant alcohol. Liver biopsy is an important part of the evaluation in term of both grade & stage. A cross sectional study was carried out in the department of Pathology, Dhaka Medical College, Dhaka & department of Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from July 2007 to June 2009. Total 55 adult subjects of both sex were included on the basis of predefined inclusion & exclusion criteria in this study to evaluate the histological pattern of non alcoholic fatty liver disease (NAFLD) and its correlation with risk factors. Liver biopsy was done and H & E and Masson's Trichrome stain slides were examined to evaluate the grade and stage of NAFLD. Scoring and semiquantitative assessment of steatosis and NAFLD severity was done according to Kleiner scale known as NAFLD activity score (NAS). The results of Pearson correlation showed only BMI and triglyceride level significantly correlated with NAS score. The results of Spearman's rank correlation showed that BMI, central obesity, triglyceridaemia and age significantly correlated with staging of fibrosis. The results of multiple regression analysis showed that variation of NAS depend on BMI and triglyceride level. The study also revealed that risk factors contributed about 29% risk for the occurrence of non alcoholic steatohepatitis.

  1. New trends on obesity and NAFLD in Asia.

    PubMed

    Fan, Jian-Gao; Kim, Seung-Up; Wong, Vincent Wai-Sun

    2017-10-01

    Traditionally, obesity and its related diseases have been considered a problem in Western countries. However, in the past two decades, urbanisation in many Asian countries has led to a sedentary lifestyle and overnutrition, setting the stage for the epidemic of obesity. This article reviews the epidemiological trend of obesity in Asia, with special emphasis on the emerging condition of non-alcoholic fatty liver disease (NAFLD). Currently, the population prevalence of NAFLD in Asia is around 25%, like many Western countries. While hepatocellular carcinoma and end-stage liver disease secondary to NAFLD remain uncommon, a rising trend has emerged. Around 8-19% of Asians with body mass indexes less than 25kg/m 2 are also found to have NAFLD, a condition often described as "lean" or "non-obese" NAFLD. Although this condition is generally less severe than that in more obese patients, steatohepatitis and fibrotic disease are well recognized. Central adiposity, insulin resistance and weight gain are major risk factors, and genetic predisposition, such as the PNPLA3 polymorphism appears to be more important in the development of NAFLD in the non-obese population. Lifestyle modification remains the cornerstone of management for obesity and NAFLD, but few patients can achieve adequate weight reduction and even fewer can maintain the weight in the long run. While pharmacological agents have entered phase III development for steatohepatitis, Asian patients are under-represented in most drug trials. Future studies should define the optimal management of obesity and NAFLD in Asia. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. Developmental origins of NAFLD: a womb with a clue

    PubMed Central

    Wesolowski, Stephanie R.; El Kasmi, Karim C.; Jonscher, Karen R.; Friedman, Jacob E.

    2017-01-01

    Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally. Deleterious exposures in utero include fetal hypoxia, increased nutrient supply, inflammation and altered gut microbiota that might produce metabolic clues, including fatty acids, metabolites, endotoxins, bile acids and cytokines, which prime the infant liver for NAFLD in a persistent manner and increase susceptibility to NASH. Mechanistic links to early disease pathways might involve shifts in lipid metabolism, mitochondrial dysfunction, pioneering gut microorganisms, macrophage programming and epigenetic changes that alter the liver microenvironment, favouring liver injury. In this Review, we discuss how maternal, fetal, neonatal and infant exposures provide developmental clues and mechanisms to help explain NAFLD acceleration and increased disease prevalence. Mechanisms identified in clinical and preclinical models suggest important opportunities for prevention and intervention that could slow down the growing epidemic of NAFLD in the next generation. PMID:27780972

  3. Factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).

    PubMed

    Tasneem, Abbas Ali; Luck, Nasir Hassan; Majid, Zain

    2018-04-01

    Introduction To determine the factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methodology All patients aged >18 years and having a fatty liver on abdominal ultrasound (US), presenting from January 2011 to January 2017, were included. A liver biopsy was performed on all the patients. Results Of 96 patients undergoing liver biopsy for non-alcoholic fatty liver disease (NAFLD), 76 (79.2%) were men. On liver US, diffuse fatty liver (DFL) was noted in 68 (70.8%) patients. Liver biopsy showed non-alcoholic steatohepatitis (NASH) in 78 (81.3%) patients. Factors associated with NASH were male gender, body mass index (BMI) > 27 kg/m 2 , DFL and raised alanine aminotransferase (ALT). A GULAB score (based on gender, US liver findings, lipid (fasting) levels, ALT level and BMI) of ≥5 predicted NASH with 82.05% sensitivity. Factors associated with advanced fibrosis in NAFLD were age >40 years, diabetes mellitus, AST/ALT ratio > 1 and raised GGT. Conclusion NASH is common in patients with male gender, high BMI, DFL on liver US, raised ALT and GULAB score ≥5.

  4. Serial combination of non-invasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with NAFLD.

    PubMed

    Petta, S; Wong, V W-S; Cammà, C; Hiriart, J-B; Wong, G L-H; Vergniol, J; Chan, A W-H; Di Marco, V; Merrouche, W; Chan, H L-Y; Marra, F; Le-Bail, B; Arena, U; Craxì, A; de Ledinghen, V

    2017-09-01

    The accuracy of available non-invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited. To assess the diagnostic performance of paired or serial combination of non-invasive tools in NAFLD patients. We analysed data from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI, AST/ALT, BARD, FIB-4, and NAFLD Fibrosis Score (NFS) scores were calculated according to published algorithms. Liver stiffness measurement (LSM) was performed by FibroScan. LSM, NFS and FIB-4 were the best non-invasive tools for staging F3-F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively), with LSM having the highest sensitivity (90%), and the highest NPV (94%), and NFS and FIB-4 the highest specificity (97% and 93%, respectively), and the highest PPV (73% and 79%, respectively). The paired combination of LSM or NFS with FIB-4 strongly reduced the likelihood of wrongly classified patients (ranging from 2.7% to 2.6%), at the price of a high uncertainty area (ranging from 54.1% to 58.2%), and of a low overall accuracy (ranging from 43% to 39.1%). The serial combination with the second test used in patients in the grey area of the first test and in those with high LSM values (>9.6 KPa) or low NFS or FIB-4 values (<-1.455 and <1.30, respectively) overall increased the diagnostic performance generating an accuracy ranging from 69.8% to 70.1%, an uncertainty area ranging from 18.9% to 20.4% and a rate of wrong classification ranging from 9.2% to 11.3%. The serial combination of LSM with FIB-4/NFS has a good diagnostic accuracy for the non-invasive diagnosis of severe fibrosis in NAFLD. © 2017 John Wiley & Sons Ltd.

  5. The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease.

    PubMed

    Petta, Salvatore; Vanni, Ester; Bugianesi, Elisabetta; Di Marco, Vito; Cammà, Calogero; Cabibi, Daniela; Mezzabotta, Lavinia; Craxì, Antonio

    2015-05-01

    The accuracy of noninvasive tools for the diagnosis of severe fibrosis in patients with nonalcoholic fatty liver disease(NAFLD) in clinical practice is still limited. We aimed at assessing the diagnostic performance of combined noninvasive tools in two independent cohorts of Italian NAFLD patients. We analysed data from 321 Italian patients(179 Sicilian-training cohort, and 142 northern Italy-validation cohort) with an histological diagnosis of NAFLD. Severe fibrosis was defined as fibrosis ≥ F3 according to Kleiner classification. The APRI, AST/ALT, BARD, FIB-4, and NFS scores were calculated according to published algorithms. Liver stiffness measurement(LSM) was performed by FibroScan. Cut-off points of LSM, NFS and FIB-4 for rule-in or rule-out F3-F4 fibrosis were calculated by the reported formulas. In the Sicilian cohort AUCs of LSM, NFS, FIB-4, LSM plus NFS, LSM plus FIB-4, and NFS plus FIB-4 were 0.857, 0.803, 0.790, 0.878, 0.888 and 0.807, respectively, while in the northern Italy cohort the corresponding AUCs were 0.848, 0.730, 0.703, 0.844, 0.850, and 0.733 respectively. In the training cohort, the combination of LSM plus NFS was the best performing strategy, providing false positive, false negative and uncertainty area rates of 0%,1.1% and 48% respectively. Similar results were obtained in the validation cohort with false positive, false negative and uncertainty area rates of 0%,7.3% and 40.8%. The combination of LSM with NFS, two complementary, easy-to-perform, and widely available tools, is able to accurately diagnose or exclude the presence of severe liver fibrosis, also reducing of about 50-60% the number of needed diagnostic liver biopsies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Omega-3 fatty acids: Mechanisms of benefit and therapeutic effects in pediatric and adult NAFLD.

    PubMed

    Nobili, Valerio; Alisi, Anna; Musso, Giovanni; Scorletti, Eleonora; Calder, Philip C; Byrne, Christopher D

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is currently considered the most common liver disease in industrialized countries, and it is estimated that it will become the most frequent indication for liver transplantation in the next decade. NAFLD may be associated with moderate (i.e. steatosis) to severe (i.e. steatohepatitis and fibrosis) liver damage and affects all age groups. Furthermore, subjects with NAFLD may be at a greater risk of other obesity-related complications later in life, and people with obesity and obesity-related complications (e.g. metabolic syndrome, type 2 diabetes and cardiovascular disease) are at increased risk of developing NAFLD. To date, there is no licensed treatment for NAFLD and therapy has been mainly centered on weight loss and increased physical activity. Unfortunately, it is often difficult for patients to adhere to the advised lifestyle changes. Therefore, based on the known pathogenesis of NAFLD, several clinical trials with different nutritional supplementation and prescribed drugs have been undertaken or are currently underway. Experimental evidence has emerged about the health benefits of omega-3 fatty acids, a group of polyunsaturated fatty acids that are important for a number of health-related functions. Omega-3 fatty acids are present in some foods (oils, nuts and seeds) that also contain omega-6 fatty acids, and the best sources of exclusively omega-3 fatty acids are oily fish, krill oil and algae. In this review, we provide a brief overview of the pathogenesis of NAFLD, and we also discuss the molecular and clinical evidence for the benefits of different omega-3 fatty acid preparations in NAFLD.

  7. Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis.

    PubMed

    McPherson, Stuart; Hardy, Tim; Dufour, Jean-Francois; Petta, Salvatore; Romero-Gomez, Manuel; Allison, Mike; Oliveira, Claudia P; Francque, Sven; Van Gaal, Luc; Schattenberg, Jörn M; Tiniakos, Dina; Burt, Alastair; Bugianesi, Elisabetta; Ratziu, Vlad; Day, Christopher P; Anstee, Quentin M

    2017-05-01

    Non-invasive fibrosis scores are widely used to identify/exclude advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). However, these scores were principally developed and validated in patients aged between 35 and 65 years of age. The objective of this study was to assess the effect of age on the performance of non-invasive fibrosis tests in NAFLD. Patients were recruited from European specialist hepatology clinics. The cohort was divided into five age-based groups: ≤35 (n=74), 36-45 (n=96), 46-55 (n=197), 56-64 (n=191), and ≥65 years (n=76), and the performance of the aspartate aminotransferase (AST)/alanine transaminase (ALT) ratio, fibrosis 4 (FIB-4), and NAFLD fibrosis score (NFS) for advanced fibrosis (stage F3-F4) for each group was assessed using liver biopsy as the standard. Six hundred and thirty-four patients were included. The diagnostic accuracy of the AST/ALT ratio was lower than NFS and FIB-4 in all the age groups. The AST/ALT ratio, NFS, and FIB-4 score performed poorly for a diagnosis of advanced fibrosis in those aged ≤35 years (area under the receiver operating characteristic curves (AUROCs 0.52, 0.52, and 0.60, respectively). For all groups >35 years, AUROCs for advanced fibrosis were similar for the NFS and FIB-4 score (range 0.77-0.84). However, the specificity for advanced fibrosis using the FIB-4 and NFS declined with age, becoming unacceptably low in those aged ≥65 years (35% for FIB-4 and 20% for NFS). New cutoffs were derived (and validated) for those aged ≥65 years, which improved specificity to 70% without adversely affecting sensitivity (FIB-4 2.0, sensitivity 77%; NFS 0.12, sensitivity 80%). The NFS and FIB-4 scores have similar accuracy for advanced fibrosis in patients aged >35 years. However, the specificity for advanced fibrosis is unacceptably low in patients aged ≥65 years, resulting in a high false positive rate. New thresholds for use in patients aged ≥65 years are proposed to address this

  8. Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis

    PubMed Central

    McPherson, Stuart; Hardy, Tim; Dufour, Jean-Francois; Petta, Salvatore; Romero-Gomez, Manuel; Allison, Mike; Oliveira, Claudia P; Francque, Sven; Van Gaal, Luc; Schattenberg, Jörn M; Tiniakos, Dina; Burt, Alastair; Bugianesi, Elisabetta; Ratziu, Vlad; Day, Christopher P; Anstee, Quentin M

    2017-01-01

    OBJECTIVES: Non-invasive fibrosis scores are widely used to identify/exclude advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). However, these scores were principally developed and validated in patients aged between 35 and 65 years of age. The objective of this study was to assess the effect of age on the performance of non-invasive fibrosis tests in NAFLD. METHODS: Patients were recruited from European specialist hepatology clinics. The cohort was divided into five age-based groups: ≤35 (n=74), 36–45 (n=96), 46–55 (n=197), 56–64 (n=191), and ≥65 years (n=76), and the performance of the aspartate aminotransferase (AST)/alanine transaminase (ALT) ratio, fibrosis 4 (FIB-4), and NAFLD fibrosis score (NFS) for advanced fibrosis (stage F3–F4) for each group was assessed using liver biopsy as the standard. RESULTS: Six hundred and thirty-four patients were included. The diagnostic accuracy of the AST/ALT ratio was lower than NFS and FIB-4 in all the age groups. The AST/ALT ratio, NFS, and FIB-4 score performed poorly for a diagnosis of advanced fibrosis in those aged ≤35 years (area under the receiver operating characteristic curves (AUROCs 0.52, 0.52, and 0.60, respectively). For all groups >35 years, AUROCs for advanced fibrosis were similar for the NFS and FIB-4 score (range 0.77–0.84). However, the specificity for advanced fibrosis using the FIB-4 and NFS declined with age, becoming unacceptably low in those aged ≥65 years (35% for FIB-4 and 20% for NFS). New cutoffs were derived (and validated) for those aged ≥65 years, which improved specificity to 70% without adversely affecting sensitivity (FIB-4 2.0, sensitivity 77% NFS 0.12, sensitivity 80%). CONCLUSIONS: The NFS and FIB-4 scores have similar accuracy for advanced fibrosis in patients aged >35 years. However, the specificity for advanced fibrosis is unacceptably low in patients aged ≥65 years, resulting in a high false positive rate. New thresholds for use in

  9. Influence of lifestyle habits, nutritional status and insulin resistance in NAFLD.

    PubMed

    Malavolti, Marcella; Battistini, Nino Carlo; Miglioli, Lucia; Bagni, Ilaria; Borelli, Luca; Marino, Mariano; Scaglioni, Federica; Bellentani, Stefano

    2012-01-01

    Non alcoholic fatty liver disease (NAFLD) is associated with obesity, diabetes and insulin resistance (IR). The aim of our study was to assess the relationship between IR, anthropometry, lifestyle habits, resting energy expenditure (REE) and degree of fatty liver at ultrasound in 48 overweight patients with NAFLD as compared to 24 controls without fatty liver, matched for age. Nutritional status, alcohol intake and physical activity were assessed by skinfold thickness measurements, a 7-day diary, and SenseWear armband (SWA). REE was assessed by both SWA (REE-SWA) and a Vmax metabolic cart (REE-Vmax). Fatty liver was measured by US and the Doppler Power Index was calculated. IR was assessed using the HOMA index. There was significant correlation between waist circumference, HOMA, Doppler power index and fatty liver grade at US. Multivariate analysis showed that alteration of waist circumference, Doppler power index, and HOMA were the major significant predictors of fatty liver. Our data demonstrated a significant association between NAFLD and central adiposity and IR.

  10. A Multidisciplinary Clinical Program is Effective in Stabilizing BMI and Reducing Transaminase Levels in Pediatric Patients with NAFLD

    PubMed Central

    DeVore, Stephanie; Kohli, Rohit; Lake, Kathleen; Nicholas, Lynda; Dietrich, Kim; Balistreri, William F.; Xanthakos, Stavra A.

    2013-01-01

    Weight loss is an effective treatment for children with non-alcoholic fatty liver disease (NAFLD) but it is very difficult to achieve outside of an intensive weight management program. We hypothesized that one can achieve success in improving NAFLD and weight-related outcomes in a structured and focused multidisciplinary clinical program feasible to implement in a gastroenterology clinic. Methods We prospectively tracked the clinical status of our patients enrolled in a multidisciplinary program of dietary and exercise advice through an Institutional Review Board-approved NAFLD registry. Each patient met with a gastroenterologist and dietician every 3 months for 30 minutes to set individualized goals and monitor progress. Results 108 children have been enrolled in the registry and of the 83 that were eligible for 1 year follow-up and included in the analysis, 39 patients returned, resulting in a 47% follow-up rate. These 39 patients showed statistically significant improvements in mean BMI z-score (−0.1 units, p<0.05), total (−11 mg/dL, p<0.05) and low density lipoprotein cholesterol (−9 mg/dL, p<0.05), and serum alanine aminotransferase (ALT) levels (−36 U/L) and aspartate amino transferase (AST) levels (−22 U/L) levels. Conclusion A clinically feasible multidisciplinary program of every 3 month 30 minute visits to set and monitor nutrition and exercise goals, stabilized mean BMI z-score and significantly improved aminotransferase levels at 1 year follow-up in obese pediatric patients with NAFLD. PMID:23518484

  11. Non-alcoholic fatty liver disease (NAFLD) and 10-year risk of cardiovascular diseases.

    PubMed

    Motamed, Nima; Rabiee, Behnam; Poustchi, Hossein; Dehestani, Babak; Hemasi, Gholam Reza; Khonsari, Mahmood Reza; Maadi, Mansooreh; Saeedian, Fatemeh Sima; Zamani, Farhad

    2017-02-01

    The association between cardiovascular diseases (CVD) and non-alcoholic fatty liver disease (NAFLD) was confirmed by a large body of evidence. This study was conducted to determine the association between NAFLD and 10-year CVD risk. This study utilized the data of 2804 subjects aged 40-74 years from a cohort study of northern Iran. Two CVD risk assessment tools, American College of Cardiology/American Heart Association and Framingham general cardiovascular risk profile for use in primary care, were utilized to determine the 10-year CVD risk in patients with NAFLD and the individuals without this condition. The mean risks were compared between these two groups. Using ACC/AHA approach, the mean risk in male participants suffering NAFLD was 14.2%, while in men without NAFLD was 11.7% (P-value < 0.0001). Using Framingham approach, the mean risks were 16.0 and 12.7% in men with and without NAFLD, respectively (P-value < 0.0001). Using ACC/AHA approach, the mean risks in female participants with and without NAFLD were 6.7 and 4.6%, respectively (P-value < 0.0001). Applying Framingham approach, the mean risk was 8.2% in women with NAFLD and 5.4% in women without NAFLD (P-value < 0.0001). The individuals with NAFLD had a higher risk of 10-year CVD events than individuals without NAFLD, according to both ACC/AHA tool and primary care version of Framingham tool. A large proportion of NAFLD patients fulfill the criteria of statin therapy recommendation, suggesting that statin therapy could reduce 10-year CVD risk in NAFLD patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

    PubMed

    Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

    2015-10-01

    Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem.

  13. Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3.

    PubMed

    Lallukka, S; Sevastianova, K; Perttilä, J; Hakkarainen, A; Orho-Melander, M; Lundbom, N; Olkkonen, V M; Yki-Järvinen, H

    2013-04-01

    The rs738409 C>G single-nucleotide polymorphism in PNPLA3 leads to a missense mutation (I148M) which increases liver fat but does not cause insulin resistance. We hypothesised that patients with non-alcoholic fatty liver disease (NAFLD) due to the PNPLA3 variant ('PNPLA3 NAFLD' = PNPLA3-148MM) do not have adipose tissue (AT) inflammation in contrast with those with NAFLD due to obesity ('obese NAFLD'). Biopsy specimens of AT were taken, and PNPLA3 genotype and liver fat ((1)H-magnetic resonance spectroscopy) were determined in 82 volunteers, who were divided into groups based on either median BMI (obese 36.2 ± 0.7 kg/m(2); non-obese 26.0 ± 0.4 kg/m(2)) or PNPLA3 genotype. All groups were similar with respect to age and sex. The PNPLA3 subgroups were equally obese (PNPLA3-148MM, 31.1 ± 1.3 kg/m(2); PNPLA3-148II, 31.2 ± 0.8 kg/m(2)), while the obese and non-obese subgroups had similar PNPLA3 genotype distribution. Gene expression of proinflammatory (MCP-1, CD68) and anti-inflammatory (Twist1, ADIPOQ) markers was measured using quantitative real-time RT-PCR. Liver fat was similarly increased in obese NAFLD (9.5 ± 1.3% vs 5.1 ± 0.9%, obese vs non-obese, p = 0.007) and PNPLA3 NAFLD (11.4 ± 1.7% vs 5.3 ± 0.8%, PNPLA3-148MM vs PNPLA3-148II, p < 0.001). Fasting serum insulin was higher in the obese than the non-obese group (76 ± 6 vs 47 ± 6 pmol/l, p < 0.001), but similar in PNPLA3-148MM and PNPLA3-148II (60 ± 8 vs 62 ± 5 pmol/l, NS). In obese vs non-obese, MCP-1 and CD68 mRNAs were upregulated, whereas those of Twist1 and ADIPOQ were significantly downregulated. AT gene expression of MCP-1, CD68, Twist1 and ADIPOQ was similar in PNPLA3-148MM and PNPLA3-148II groups. PNPLA3 NAFLD is characterised by an increase in liver fat but no insulin resistance or AT inflammation, while obese NAFLD has all three of these features.

  14. Non-alcoholic fatty liver disease (Nafld) in obese children- effect of refined carbohydrates in diet.

    PubMed

    Félix, Deise Rosa; Costenaro, Fabiola; Gottschall, Catarina Bertaso Andreatta; Coral, Gabriela Perdomo

    2016-11-15

    The incidence of childhood obesity has increased progressively and, associated with this, nonalcoholic fatty liver disease (NAFLD) has often been diagnosed in this age group. To determine the risk factors associated with NAFLD in obese children, with special emphasis on diet. A prospective cross-sectional study was conducted with obese children referred to the endocrinology outpatient clinic. Questions about dietary habits and physical activity were applied. In addition, two 24 h food recalls were collected. Anthropometric measurements, biochemical tests and abdominal ultrasound were obtained. The study was approved by the institutional review board of Irmandade Santa Casa de Misericórdia de Porto Alegre Hospital (ISCMPA). A 5% statistical significance level was considered statistically significant. Of 55 patients initially allocated, 39 were evaluated and 8 (20.5%) had a diagnosis of NAFLD, which was more prevalent among boys (87.5%). Logistic regression analysis showed that the predictive factors independently associated with the presence of NAFLD were male gender (OR: 1.62; 95% CI: 1.08- 2.44; p = 0.038); high amount of refined carbohydrates in the diet (OR: 2.17; 95% CI: 1.05 - 6.82; p = 0.038) and absence of routine physical activity (OR: 3.35; 95% CI:1.97 - 0.006; p = 0.006). The prevalence of NAFLD in obese children in our series was high. Furthermore, the high amount of refined carbohydrates in the diet, male gender and sedentary lifestyle were significant risk factors for its occurrence.

  15. Controversies in the Diagnosis and Management of NAFLD and NASH.

    PubMed

    Rinella, Mary E; Loomba, Rohit; Caldwell, Stephen H; Kowdley, Kris; Charlton, Michael; Tetri, Brent; Harrison, Stephen A

    2014-04-01

    Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of chronic liver disease in the United States. Nonalcoholic steatohepatitis (NASH) occurs in a subset of patients with NAFLD and is characterized by the presence of hepa-tocellular injury, which is progressive in a substantial proportion of cases and can lead to cirrhosis and all of its complications. Although the diagnosis of NAFLD can be made through imaging studies or liver biopsy, the diagnosis of NASH still requires histologic confirmation. Liver biopsy should be performed in the presence of risk factors for advanced disease. Measures aimed at promoting weight loss, a healthier lifestyle, and optimization of metabolic risk factors remain the cornerstone of management of NAFLD. Therapeutic agents that are presently considered the most promising in NAFLD are effective in less than 50% of patients. Among patients with biopsy-proven NASH, treatment with pharmacologic agents should be considered; however, the role of specific agents in NASH still needs further study. Despite a wealth of research over the past 15 years, many controversies remain with respect to the diagnosis and management of NAFLD and NASH as well as the influence of alcohol on liver disease progression in these patients.

  16. Sinusoidal Endothelial Dysfunction Precedes Inflammation and Fibrosis in a Model of NAFLD

    PubMed Central

    Pasarín, Marcos; La Mura, Vincenzo; Gracia-Sancho, Jorge; García-Calderó, Héctor; Rodríguez-Vilarrupla, Aina; García-Pagán, Juan Carlos; Bosch, Jaime; Abraldes, Juan G.

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Most morbidity associated with the metabolic syndrome is related to vascular complications, in which endothelial dysfunction is a major pathogenic factor. However, whether NAFLD is associated with endothelial dysfunction within the hepatic vasculature is unknown. The aims of this study were to explore, in a model of diet-induced overweight that expresses most features of the metabolic syndrome, whether early NAFLD is associated with liver endothelial dysfunction. Wistar Kyoto rats were fed a cafeteria diet (CafD; 65% of fat, mostly saturated) or a control diet (CD) for 1 month. CafD rats developed features of the metabolic syndrome (overweight, arterial hypertension, hypertryglyceridemia, hyperglucemia and insulin resistance) and liver steatosis without inflammation or fibrosis. CafD rats had a significantly higher in vivo hepatic vascular resistance than CD. In liver perfusion livers from CafD rats had an increased portal perfusion pressure and decreased endothelium-dependent vasodilation. This was associated with a decreased Akt-dependent eNOS phosphorylation and NOS activity. In summary, we demonstrate in a rat model of the metabolic syndrome that shows features of NAFLD, that liver endothelial dysfunction occurs before the development of fibrosis or inflammation. PMID:22509248

  17. In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores.

    PubMed

    Schwimmer, Jeffrey B; Lavine, Joel E; Wilson, Laura A; Neuschwander-Tetri, Brent A; Xanthakos, Stavra A; Kohli, Rohit; Barlow, Sarah E; Vos, Miriam B; Karpen, Saul J; Molleston, Jean P; Whitington, Peter F; Rosenthal, Philip; Jain, Ajay K; Murray, Karen F; Brunt, Elizabeth M; Kleiner, David E; Van Natta, Mark L; Clark, Jeanne M; Tonascia, James; Doo, Edward

    2016-12-01

    No treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD. We performed a double-masked trial of 169 children with NAFLD activity scores of 4 or higher at 10 centers. From June 2012 to January 2014, the patients were assigned randomly to receive CBDR or placebo twice daily (300 mg for patients weighing ≤65 kg, 375 mg for patients weighing >65 to 80 kg, and 450 mg for patients weighing >80 kg) for 52 weeks. The primary outcome from the intention-to-treat analysis was improvement in liver histology over 52 weeks, defined as a decrease in the NAFLD activity score of 2 points or more without worsening fibrosis; patients without biopsy specimens from week 52 (17 in the CBDR group and 6 in the placebo group) were considered nonresponders. We calculated the relative risks (RR) of improvement using a stratified Cochran-Mantel-Haenszel analysis. There was no significant difference between groups in the primary outcome (28% of children in the CBDR group vs 22% in the placebo group; RR, 1.3; 95% confidence interval [CI], 0.8-2.1; P = .34). However, children receiving CBDR had significant changes in prespecified secondary outcomes: reduced mean levels of alanine aminotransferase (reduction, 53 ± 88 U/L vs 8 ± 77 U/L in the placebo group; P = .02) and aspartate aminotransferase (reduction, 31 ± 52 vs 4 ± 36 U/L in the placebo group; P = .008), and a larger proportion had reduced lobular inflammation (36% in the CBDR group vs 21% in the placebo group; RR, 1.8; 95% CI, 1.1-2.9; P = .03). In a post hoc analysis of children weighing 65 kg or less, those taking CBDR had a 4-fold better chance of histologic improvement (observed in 50% of children in the CBDR group vs 13% in the placebo group; RR, 4.0; 95% CI, 1.3-12.3; P = .005). In a randomized

  18. Alternation of plasma fatty acids composition and desaturase activities in children with liver steatosis

    PubMed Central

    Su, Hui-Min; Yao, Tsung-Chieh; Kuo, Ming-Ling; Lai, Ming-Wei; Tsai, Ming-Han; Huang, Jing-Long

    2017-01-01

    Objective The aim of this study was to investigate changes in plasma fatty acids proportions and estimated desaturase activities for variable grading of liver steatosis in children. Methods In total, 111 schoolchildren (aged 8–18 years) were included in the analysis from March 2015 to August 2016. Anthropometric evaluation, liver ultrasound examination and scoring for nonalcoholic fatty liver disease (NAFLD score = 0–6), and biochemical and plasma fatty acids analysis were performed. We compared the composition ratio of fatty acids between children with high-grade liver steatosis (NAFLD score = 4–6), low-grade liver steatosis (NAFLD score = 1–3), and healthy controls (NAFLD score = 0). In addition, correlation coefficients (r) between NAFLD score, metabolic variables, and estimated activity of desaturase indices (stearoyl-coenzyme A desaturase-1 (SCD1), delta-5 and delta-6 desaturase) were calculated. Results Compared with healthy controls, children with liver steatosis showed a higher proportion of monounsaturated fatty acids (21.16 ± 2.81% vs. 19.68 ± 2.71%, p = 0.024). In addition, children with high- grade liver steatosis exhibited higher proportions of palmitic acid (C16:0), palmitoleic acid (C16:1n-7), dihomo-γ-linolenic acid (C20:3n-6), adrenic acid (C22:4n-6), and docosapentaenoic acid (C22:5n-6); and lower proportions of eicosapentaenoic acid (C20:5n-3) (P< 0.05). In all subjects, the NAFLD score was positively correlated with body mass index (BMI) (kg/m2) (r = 0.696), homeostasis model of assessment ratio–index (HOMA-IR) (r = 0.510), SCD1(16) (r = 0.273), and the delta-6 index (r = 0.494); and inversely associated with the delta-5 index (r = -0.443). Conclusion Our current data suggested that children with liver steatosis was highly associated with obesity, and insulin resistance. In addition, increased endogenous lipogenesis through altered desaturase activity may contribute to the progression of liver steatosis in children. PMID:28759573

  19. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD).

    PubMed

    Buzzetti, Elena; Pinzani, Massimo; Tsochatzis, Emmanuel A

    2016-08-01

    Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance.

    PubMed

    Gaggini, Melania; Carli, Fabrizia; Rosso, Chiara; Buzzigoli, Emma; Marietti, Milena; Della Latta, Veronica; Ciociaro, Demetrio; Abate, Maria Lorena; Gambino, Roberto; Cassader, Maurizio; Bugianesi, Elisabetta; Gastaldelli, Amalia

    2018-01-01

    Plasma concentrations of amino acids (AAs), in particular, branched chain AAs (BCAAs), are often found increased in nonalcoholic fatty liver disease (NAFLD); however, if this is due to increased muscular protein catabolism, obesity, and/or increased insulin resistance (IR) or impaired tissue metabolism is unknown. Thus, we evaluated a) if subjects with NAFLD without obesity (NAFLD-NO) compared to those with obesity (NAFLD-Ob) display altered plasma AAs compared to controls (CTs); and b) if AA concentrations are associated with IR and liver histology. Glutamic acid, serine, and glycine concentrations are known to be altered in NAFLD. Because these AAs are involved in glutathione synthesis, we hypothesized they might be related to the severity of NAFLD. We therefore measured the AA profile of 44 subjects with NAFLD without diabetes and who had a liver biopsy (29 NAFLD-NO and 15 NAFLD-Ob) and 20 CTs without obesity, by gas chromatography-mass spectrometry, homeostasis model assessment of insulin resistance, hepatic IR (Hep-IR; Hep-IR = endogenous glucose production × insulin), and the new glutamate-serine-glycine (GSG) index (glutamate/[serine + glycine]) and tested for an association with liver histology. Most AAs were increased only in NAFLD-Ob subjects. Only alanine, glutamate, isoleucine, and valine, but not leucine, were increased in NAFLD-NO subjects compared to CTs. Glutamate, tyrosine, and the GSG-index were correlated with Hep-IR. The GSG-index correlated with liver enzymes, in particular, gamma-glutamyltransferase (R = 0.70), independent of body mass index. Ballooning and/or inflammation at liver biopsy were associated with increased plasma BCAAs and aromatic AAs and were mildly associated with the GSG-index, while only the new GSG-index was able to discriminate fibrosis F3-4 from F0-2 in this cohort. Increased plasma AA concentrations were observed mainly in subjects with obesity and NAFLD, likely as a consequence of increased IR and protein catabolism

  1. Targeting Lifestyle Behavior Change in Adults with NAFLD During a 20-min Consultation: Summary of the Dietary and Exercise Literature.

    PubMed

    Hallsworth, Kate; Avery, Leah; Trenell, Michael I

    2016-03-01

    Non-alcoholic fatty liver disease (NAFLD) is largely linked to poor diet, lack of physical activity/exercise, and being overweight. In the absence of approved pharmaceutical agents, lifestyle modification, encompassing dietary change and increased physical activity/exercise to initiate weight loss, is the recommended therapy for NAFLD. Despite this, the use of lifestyle therapy within clinical settings is lacking with limited guidance available about what it should involve, how it should be delivered, and whether it can be feasibly delivered as part of standard care. This paper highlights the evidence for the use of lifestyle modification in NAFLD. While there is evidence to support use of behavioral strategies to support lifestyle behavior change in other clinical populations, these are yet to be assessed in people with NAFLD. However, there is sufficient evidence to suggest that behavioral intervention targeting diet and physical activity to promote weight loss in general is effective and a number of practical strategies are presented on how this could be achieved.

  2. Serum metabonomics of NAFLD plus T2DM based on liquid chromatography-mass spectrometry.

    PubMed

    Chen, Yang; Li, Chunlong; Liu, Liyan; Guo, Fuchuan; Li, Songtao; Huang, Lina; Sun, Changhao; Feng, Rennan

    2016-09-01

    Nonalcoholic fatty liver disease (NAFLD), a main liver disease around the world, is closely associated with insulin resistance, type 2 diabetes mellitus (T2DM) and other metabolic diseases. The objective of this study is to identify distinct metabolites of NAFLD patients with or without T2DM. We used a biomarker-discovery population to find distinct metabolites of NAFLD patients with or without T2DM. Then, a validation population was applied to test the model of the biomarker-discovery population. All the individuals received anthropometric and common biochemical measurements. The metabolic data were analyzed by multivariable statistical analyses using ultra-high-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry. There were 7, 7, 2 metabolites in the positive electrospray ionization (ESI(+)) mode, which were identified between groups from both the biomarker-discovery and validation population. The NAFLD group showed higher concentrations of oleamide, l-phenylalanine, l-proline, bilirubin, l-palmitoylcarnitine, and PC (20:5) and a lower concentration of Lyso-PAF C-18 than those of control. Compared with the control group, the NAFLD+T2DM group displayed higher oleamide, l-leucine, LysoPC (14:0), bilirubin, tetradecenoylcarnitine, linoleyl carnitine, and tetradecadiencarnitine in serum. Tetradecenoylcarnitine and tetradecadiencarnitine were more elevated in patients with NAFLD+T2DM than in the NAFLD group. Serum metabonomic analyses displayed great metabolic changes in patients with NAFLD and NAFLD plus T2DM. Our study is beneficial in providing a further view into the pathogenesis and pathophysiology of NAFLD and NAFLD plus T2DM, which might be useful for the prevention and therapy of NAFLD and NAFLD plus T2DM. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  3. Diet-Quality Scores and Prevalence of Nonalcoholic Fatty Liver Disease: A Population Study Using Proton-Magnetic Resonance Spectroscopy

    PubMed Central

    Chan, Ruth; Wong, Vincent Wai-Sun; Chu, Winnie Chiu-Wing; Wong, Grace Lai-Hung; Li, Liz Sin; Leung, Jason; Chim, Angel Mei-Ling; Yeung, David Ka-Wai; Sea, Mandy Man-Mei; Woo, Jean; Chan, Francis Ka-Leung; Chan, Henry Lik-Yuen

    2015-01-01

    Dietary pattern analysis is an alternative approach to examine the association between diet and nonalcoholic fatty liver disease (NAFLD). This study examined the association of two diet-quality scores, namely Diet Quality Index-International (DQI-I) and Mediterranean Diet Score (MDS) with NAFLD prevalence. Apparently healthy Chinese adults (332 male, 465 female) aged 18 years or above were recruited through a population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. DQI-I and MDS, as well as major food group and nutrient intakes were calculated based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at ≥5% by proton-magnetic resonance spectroscopy. Multivariate logistic regression models were used to examine the association between each diet-quality score or dietary component and prevalent NAFLD with adjustment for potential lifestyle, metabolic and genetic factors. A total of 220 subjects (27.6%) were diagnosed with NAFLD. DQI-I but not MDS was associated with the prevalence of NAFLD. A 10-unit decrease in DQI-I was associated with 24% increase in the likelihood of having NAFLD in the age and sex adjusted model (95% CI: 1.06–1.45, p = 0.009), and the association remained significant when the model was further adjusted for other lifestyle factors, metabolic and genetic factors [OR: 1.26 (95% CI: 1.03–1.54), p = 0.027]. Multivariate regression analyses showed an inverse association of the intake of vegetables and legumes, fruits and dried fruits, as well as vitamin C with the NAFLD prevalence (p<0.05). In conclusion, a better diet quality as characterized by a higher DQI-I and a higher consumption of vegetables, legumes and fruits was associated with a reduced likelihood of having NAFLD in Hong Kong Chinese. PMID:26418083

  4. Diagnosis of non-alcoholic fatty liver disease (NAFLD).

    PubMed

    Yki-Järvinen, Hannele

    2016-06-01

    Non-alcoholic fatty liver disease (NAFLD) increases risk of mortality from liver and cardiovascular disease (CVD) and is the major cause of hepatocellular carcinoma (HCC), which may develop without cirrhosis. NAFLD predicts type 2 diabetes, even independently of obesity. Globally, the prevalence of NAFLD averages 25% and is as common as the metabolic syndrome. The majority of patients with type 2 diabetes have NAFLD. The challenge for the diabetologist is to identify patients at risk of advanced liver disease and HCC. At a minimum, liver function tests (LFTs), despite being neither specific nor sensitive, should be performed in all patients with the metabolic syndrome or type 2 diabetes. Increases in LFTs, for which the updated reference values are lower (serum ALT ≈30 U/l in men and ≈20 U/l in women) than those hitherto used in many laboratories, should prompt assessment of fibrosis biomarkers and referral of individuals at risk to a NAFLD/hepatology clinic. Preferably, evaluation of NAFLD should be based on measurement of steatosis biomarkers or ultrasound if easily available. A large number of individuals carry the patatin-like phospholipase domain containing 3 (PNPLA3) I148M variant (30-50%) or the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant (11-15%). These variants increase the risk of advanced liver disease and HCC but not of diabetes or CVD. Genotyping of selected patients for these variants is recommended. Many patients have 'double trouble', i.e. carry both a genetic risk factor and have the metabolic syndrome. Excess use of alcohol could be a cause of 'triple trouble', but such patients would be classified as having alcoholic fatty liver disease. This review summarises a presentation given at the symposium 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1 , and by John Jones, DOI: 10.1007/s00125

  5. IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD - a pilot study.

    PubMed

    Hagström, Hannes; Stål, Per; Hultcrantz, Rolf; Brismar, Kerstin; Ansurudeen, Ishrath

    2017-12-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. Advanced fibrosis (stage 3-4) is the most robust marker for future mortality, but diagnosis requires liver biopsy. Current non-invasive scoring systems aimed to identify advanced fibrosis are imperfect. Insulin-like growth factor I (IGF-I) and its binding protein IGFBP-1 are liver derived proteins, that are involved in various liver disorders. The aim of this study was to examine the possible association between advanced fibrosis and IGF-I and IGFBP-1 in NAFLD. Fasting blood samples were obtained from 52 patients diagnosed with NAFLD by liver biopsy. Total IGF-I and IGFBP-1 concentrations were determined in serum by in-house radio-immuno-assays. IGF-I levels were age-standardized (IGF-SD). A logistic regression model was used to investigate the association of IGF-SD and IGFBP-1 with advanced fibrosis (stage 3-4). Patients with advanced fibrosis (stage 3-4 vs. 0-2) had lower IGF-SD (-1.17 vs. 0.11, p = .01) and higher mean levels of IGFBP-1 (29.9 vs. 18.8 µg/l, p = .02). IGFBP-1 was associated with presence of advanced fibrosis (OR 1.04 per unit increase, 95%CI 1.0-1.07, p = .05), while IGF-1 was negatively associated with advanced fibrosis (OR 0.63 per standard deviation, 95%CI 0.44-0.92, p = .02). This pilot study suggests an association between serum IGFBP-1 and IGF-I levels with advanced fibrosis in NAFLD patients. IGFBP1 and IGF-1 could be of interest as future biomarkers. Similar studies in larger cohorts are needed.

  6. Nursing activities score.

    PubMed

    Miranda, Dinis Reis; Nap, Raoul; de Rijk, Angelique; Schaufeli, Wilmar; Iapichino, Gaetano

    2003-02-01

    The instruments used for measuring nursing workload in the intensive care unit (e.g., Therapeutic Intervention Scoring System-28) are based on therapeutic interventions related to severity of illness. Many nursing activities are not necessarily related to severity of illness, and cost-effectiveness studies require the accurate evaluation of nursing activities. The aim of the study was to determine the nursing activities that best describe workload in the intensive care unit and to attribute weights to these activities so that the score describes average time consumption instead of severity of illness. To define by consensus a list of nursing activities, to determine the average time consumption of these activities by use of a 1-wk observational cross-sectional study, and to compare these results with those of the Therapeutic Intervention Scoring System-28. A total of 99 intensive care units in 15 countries. Consecutive admissions to the intensive care units. Daily recording of nursing activities at a patient level and random multimoment recording of these activities. A total of five new items and 14 subitems describing nursing activities in the intensive care unit (e.g., monitoring, care of relatives, administrative tasks) were added to the list of therapeutic interventions in Therapeutic Intervention Scoring System-28. Data from 2,041 patients (6,451 nursing days and 127,951 multimoment recordings) were analyzed. The new activities accounted for 60% of the average nursing time; the new scoring system (Nursing Activities Score) explained 81% of the nursing time (vs. 43% in Therapeutic Intervention Scoring System-28). The weights in the Therapeutic Intervention Scoring System-28 are not derived from the use of nursing time. Our study suggests that the Nursing Activities Score measures the consumption of nursing time in the intensive care unit. These results should be validated in independent databases.

  7. NAFLD prevalence differs among hispanic subgroups: the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Fleischman, Michael Wayne; Budoff, Matthew; Zeb, Ifran; Li, Dong; Foster, Temitope

    2014-05-07

    To compare prevalence rates of non-alcoholic fatty liver disease (NAFLD) between Hispanics of Mexican origin and Hispanics of Dominican and Puerto Rican origin. We evaluated prevalence rates of NAFLD between the two largest sub-populations of Hispanics in the United States; Hispanics of Mexican origin and Hispanics of Caribbean origin (Dominican and Puerto Rican), in the multi-ethnic study of atherosclerosis (MESA) cohort. MESA is a large, population based, multi-center cohort study comprised of 6814 healthy Caucasian, African-American, Hispanic, and Asian men and women aged 45-84. We utilized the baseline serum, anthropometric and radiographic measurements obtained between 2000 and 2002. NAFLD was measured via computed tomography scan and was defined as liver/spleen attenuation ratio < 1. There were 788 Hispanic participants included in the study after exclusions. The prevalence of NAFLD was 29% (n = 225). Hispanics of Mexican origin had a significantly higher prevalence of NAFLD (33%), compared to Hispanics of Dominican origin (16%), (P < 0.01) and Hispanics of Puerto Rican origin (18%), (P < 0.01). After controlling for age, sex, BMI, waist circumference, hypertension, serum HDL, triglyceride and CRP level and insulin resistance, Hispanics of Mexican origin remained significantly more likely to have NAFLD than those of Dominican and Puerto Rican origin. United States Hispanics of Mexican origin have a significantly higher prevalence of NAFLD when compared to United States Hispanics of Dominican or Puerto Rican origin after controlling for known risk factors. Care should be taken when performing risk assessment in Hispanic populations not to make assumptions of homogeneity.

  8. Association of Sleep Disorders with Nonalcoholic Fatty Liver Disease (NAFLD): A Population-based Study.

    PubMed

    Mir, Heshaam M; Stepanova, Maria; Afendy, Hena; Cable, Rebecca; Younossi, Zobair M

    2013-09-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. In smaller studies, sleep apnea has been previously associated with NAFLD. The aim of this study was to assess the prevalence and independent associations of sleep disorders in patients with NAFLD using recent population-based data. Three cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010 were used. The diagnosis of NAFLD was established as elevated liver enzymes in the absence of all other causes of chronic liver disease. Sleep disorders were diagnosed using sleep disorder questionnaires completed by NHANES participants, and included self-reported history of sleep apnea, insomnia, and restless leg syndrome. The prevalence of sleep disorders was compared between those with and without NAFLD. A total of 10,541 adult NHANES participants with complete demographic, clinical, and laboratory data were included. Of those, 15.0% had NAFLD and 7.2% reported having sleep disorders. Of those with sleep disorders, 64.7% reported history of sleep apnea, 16.0% had history of insomnia, and 4.0% had restless leg syndrome. Individuals with NAFLD were more likely to be male (53.8% vs. 45.7%, P < 0.0001), obese (50.1% vs. 33.4%, P < 0.0001) and had higher prevalence of sleep disorders (9.1% vs. 6.9%, P = 0.0118). In multivariate analysis, having any sleep disorder, sleep apnea and insomnia were all independently associated with NAFLD [OR (95% CI) = 1.40 (1.11-1.76), OR = 1.39 (0.98-1.97), and OR = 2.17 (1.19-3.95); respectively)]. This large population-based data suggests that NAFLD is associated with sleep disorders. Although the exact mechanism is unknown, this association is most likely through metabolic conditions associated with NAFLD.

  9. Association of Sleep Disorders with Nonalcoholic Fatty Liver Disease (NAFLD): A Population-based Study

    PubMed Central

    Mir, Heshaam M.; Stepanova, Maria; Afendy, Hena; Cable, Rebecca; Younossi, Zobair M.

    2013-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. In smaller studies, sleep apnea has been previously associated with NAFLD. The aim of this study was to assess the prevalence and independent associations of sleep disorders in patients with NAFLD using recent population-based data. Methods Three cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010 were used. The diagnosis of NAFLD was established as elevated liver enzymes in the absence of all other causes of chronic liver disease. Sleep disorders were diagnosed using sleep disorder questionnaires completed by NHANES participants, and included self-reported history of sleep apnea, insomnia, and restless leg syndrome. The prevalence of sleep disorders was compared between those with and without NAFLD. Results A total of 10,541 adult NHANES participants with complete demographic, clinical, and laboratory data were included. Of those, 15.0% had NAFLD and 7.2% reported having sleep disorders. Of those with sleep disorders, 64.7% reported history of sleep apnea, 16.0% had history of insomnia, and 4.0% had restless leg syndrome. Individuals with NAFLD were more likely to be male (53.8% vs. 45.7%, P < 0.0001), obese (50.1% vs. 33.4%, P < 0.0001) and had higher prevalence of sleep disorders (9.1% vs. 6.9%, P = 0.0118). In multivariate analysis, having any sleep disorder, sleep apnea and insomnia were all independently associated with NAFLD [OR (95% CI) = 1.40 (1.11–1.76), OR = 1.39 (0.98–1.97), and OR = 2.17 (1.19–3.95); respectively)]. Conclusions This large population-based data suggests that NAFLD is associated with sleep disorders. Although the exact mechanism is unknown, this association is most likely through metabolic conditions associated with NAFLD. PMID:25755498

  10. Biomarkers of NAFLD progression: a lipidomics approach to an epidemic.

    PubMed

    Gorden, D Lee; Myers, David S; Ivanova, Pavlina T; Fahy, Eoin; Maurya, Mano R; Gupta, Shakti; Min, Jun; Spann, Nathanael J; McDonald, Jeffrey G; Kelly, Samuel L; Duan, Jingjing; Sullards, M Cameron; Leiker, Thomas J; Barkley, Robert M; Quehenberger, Oswald; Armando, Aaron M; Milne, Stephen B; Mathews, Thomas P; Armstrong, Michelle D; Li, Chijun; Melvin, Willie V; Clements, Ronald H; Washington, M Kay; Mendonsa, Alisha M; Witztum, Joseph L; Guan, Ziqiang; Glass, Christopher K; Murphy, Robert C; Dennis, Edward A; Merrill, Alfred H; Russell, David W; Subramaniam, Shankar; Brown, H Alex

    2015-03-01

    The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  11. Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study.

    PubMed

    Tuttolomondo, Antonino; Petta, Salvatore; Casuccio, Alessandra; Maida, Carlo; Corte, Vittoriano Della; Daidone, Mario; Di Raimondo, Domenico; Pecoraro, Rosaria; Fonte, Roberto; Cirrincione, Anna; Zafonte, Rita; Cabibi, Daniela; Cammà, Calogero; Di Marco, Vito; Licata, Anna; Magliozzo, Franco; Marchesini, Giulio; Merlino, Giovanni; Craxì, Antonio; Pinto, Antonio

    2018-02-16

    No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (RHI). The mini-mental state examination (MMSE) was administered to test cognitive performance. 80 consecutive patients with biopsy-proven NAFLD and 83 controls without fatty liver disease. NAFLD subjects showed significantly lower mean RHI, higher mean arterial stiffness indexes and lower mean MMSE score. Multivariable analysis after correction for BMI, dyslipidaemia, hypertension, sex, diabetes, age and cardiovascular disease showed that BMI, diastolic blood pressure and RHI are significantly associated to NAFLD. Simple linear regression analysis showed among non-alcoholic steatohepatitis (NASH) subjects a significant negative relationship between ballooning grade and MMSE and a significant positive association between Kleiner steatosis grade and augmentation index. Future research will be addressed to evaluate the relationship between inflammatory markers and arterial stiffness and endothelial function indexes in NAFLD subjects. These study will evaluate association between cardiovascular event incidence and arterial stiffness, endothelial and cognitive markers, and they will address the beneficial effects of cardiovascular drugs such as statins and ACE inhibitors on these surrogate markers in NAFLD subjects.

  12. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity

    PubMed Central

    Henao-Mejia, Jorge; Elinav, Eran; Jin, Cheng-Cheng; Hao, Liming; Mehal, Wajahat Z.; Strowig, Till; Thaiss, Christoph A.; Kau, Andrew L.; Eisenbarth, Stephanie C.; Jurczak, Michael J.; Camporez, Joao-Paulo; Shulman, Gerald I.; Gordon, Jeffrey I.; Hoffman, Hal M.; Flavell, Richard A.

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty percent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different animal models reveal that inflammasome deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic TNF-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient animals to wild type mice results in exacerbation of hepatic steatosis, glucose intolerance, and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders. PMID:22297845

  13. Diet, Microbiota, Obesity, and NAFLD: A Dangerous Quartet

    PubMed Central

    Machado, Mariana Verdelho; Cortez-Pinto, Helena

    2016-01-01

    Recently, the importance of the gut-liver-adipose tissue axis has become evident. Nonalcoholic fatty liver disease (NAFLD) is the hepatic disease of a systemic metabolic disorder that radiates from energy-surplus induced adiposopathy. The gut microbiota has tremendous influences in our whole-body metabolism, and is crucial for our well-being and health. Microorganisms precede humans in more than 400 million years and our guest flora evolved with us in order to help us face aggressor microorganisms, to help us maximize the energy that can be extracted from nutrients, and to produce essential nutrients/vitamins that we are not equipped to produce. However, our gut microbiota can be disturbed, dysbiota, and become itself a source of stress and injury. Dysbiota may adversely impact metabolism and immune responses favoring obesity and obesity-related disorders such as insulin resistance/diabetes mellitus and NAFLD. In this review, we will summarize the latest evidence of the role of microbiota/dysbiota in diet-induced obesity and NAFLD, as well as the potential therapeutic role of targeting the microbiota in this set. PMID:27043550

  14. Non-alcoholic fatty liver disease - histological scoring systems: a large cohort single-center, evaluation study.

    PubMed

    Rastogi, Archana; Shasthry, Saggere Muralikrishna; Agarwal, Ayushi; Bihari, Chhagan; Jain, Priyanka; Jindal, Ankur; Sarin, Shiv

    2017-11-01

    Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver disease. Till date, liver biopsy remains the gold standard for identification and quantification of the wide histological spectra of NAFLD. Histological scorings are very useful and widely applied for the diagnosis and management in clinical trials and follow-up studies of non-alcoholic steatohepatitis (NASH). However, in view of scarce published literature, there is a need to evaluate them in large cohort of NAFLD. This study was aimed to evaluate the two histological scoring systems (NAS-CRN, SAF) in the diagnosis of NAFLD and to assess the role of histological characteristics as injury markers in NAFLD. Retrospective histological study of liver biopsies of 1000 patients diagnosed as NAFLD, between 2010 and 2016, was conducted. Histopathologic evaluation and semiquantiative scoring based on NAS-CRN and SAF algorithm and their correlation with serum aminotransferase and fibrosis were performed. Liver biopsies were classified according to the NAS-CRN scoring, as NAS <3 (not NASH) in 72 (7.2%), NAS 3-4 (borderline NASH) in 310 (31%), and NAS ≥5 (definite NASH) in 618 (61.8%), and SAF classified 117 (11.7%) not NASH and 883 (88.3%) definite NASH. There was excellent concordance for definite NASH and not NASH; however, 88.06% of borderline NASH was classified as NASH by SAF. 76.39% by NAS and 78.63% by SAF algorithm who were diagnosed as not NASH showed the presence of fibrosis; however, higher stages of fibrosis were significantly more prevalent in definite NASH, excluding burnt-out cirrhosis. Serum ALT was significantly associated with increasing stages of fibrosis (p < 0.001) and the three categories (not NASH, borderline NASH, and definite NASH) when classified as with/without fibrosis (p < 0.001). Steatosis of higher grades, more ballooned cells, and more foci of Lobular Inflammation were found in significantly higher proportion of patients with NASH (p < 0

  15. Endoplasmic reticulum stress related molecular mechanisms in nonalcoholic fatty liver disease (NAFLD).

    PubMed

    Wang, Lifeng; Chen, J; Ning, C; Lei, D; Ren, Jun

    2018-05-16

    Non-alcoholic fatty liver disease (NAFLD) has emerged as a common public health problem and a common cause of chronic liver diseases. However, the underlying mechanisms leading to the development and progression of NAFLD remain elusive. Accumulating evidence has depicted an essential role for endoplasmic reticulum (ER) stress in the development of steatosis and later progression into nonalcoholic steatohepatitis and hepatocarcinoma. With the accumulation of unfolded and misfolded proteins in the ER lumen, ER stress is provoked to turn on the unfolded protein response (UPR). ER stress triggers a cascade reaction of transcriptional and translational events that restore ER homeostasis, promoting cell survival and adaptation. However, prolonged ER stress may be transit physiological mechanisms to pathological consequences, including insulin resistance, fat accumulation, inflammation, apoptosis, and autophagy, all of which with important roles in the development of NAFLD. Therefore, understanding the role of ER stress in the onset and pathogenesis of NAFLD is pertinent to the management of this devastating metabolic disease. Here we will summarize available information on recent findings linking ER stress to the pathogenesis of NAFLD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Non-alcoholic fatty liver disease fibrosis score and FIB-4 scoring system could identify patients at risk of systemic complications.

    PubMed

    Takahashi, Yuka; Kurosaki, Masayuki; Tamaki, Nobuharu; Yasui, Yutaka; Hosokawa, Takanori; Tsuchiya, Kaoru; Nakanishi, Hiroyuki; Itakura, Jun; Izumi, Namiki

    2015-06-01

    To investigate the relation between systemic complications of non-alcoholic fatty liver disease (NAFLD) and non-invasive fibrosis scores. The NAFLD fibrosis score (NFS) and FIB-4 were measured in 1559 people who underwent a complete medical checkup at our hospital and were followed for more than 3 years. Correlation between these scores and prevalence and new incidence rates of diabetes or cerebral-cardiovascular diseases were analyzed. The 1559 cases were classified into two groups using the low cut-off values of NFS and FIB-4: group 1 (≥low cut-off score with fatty liver) and group 2 (the others). In group 1, the prevalence of diabetes and cerebral-cardiovascular diseases at baseline and additional incidences during the observation period was higher compared with group 2. Diabetes at baseline in group 1 versus group 2 were 31.5% versus 3.1% (NFS, P < 0.0001), 17.0% versus 4.7% (FIB-4, P < 0.0001), and cerebral-cardiovascular diseases at baseline were 7.7% versus 2.3% (NFS, P = 0.002) and 9.0% versus 2.3% (FIB-4, P = 0.0012). New incidences of diabetes were 4.5% versus 1.2% (NFS, P = 0.034) and 3.6% versus 1.2% (FIB-4, P = 0.11), and of cerebral-cardiovascular diseases were 5.0% versus 0.9% (NFS, P = 0.0019) and 5.4% versus 0.9% (FIB-4, P = 0.0034). NFS and FIB-4 are useful to extract cases with high risk of systemic complications of NAFLD in the public. © 2014 The Japan Society of Hepatology.

  17. Consensus document. Management of non-alcoholic fatty liver disease (NAFLD). Clinical practice guideline.

    PubMed

    Aller, Rocío; Fernández-Rodríguez, Conrado; Lo Iacono, Oreste; Bañares, Rafael; Abad, Javier; Carrión, José Antonio; García-Monzón, Carmelo; Caballería, Joan; Berenguer, Marina; Rodríguez-Perálvarez, Manuel; Miranda, José López; Vilar-Gómez, Eduardo; Crespo, Javier; García-Cortés, Miren; Reig, María; Navarro, José María; Gallego, Rocío; Genescà, Joan; Arias-Loste, María Teresa; Pareja, María Jesús; Albillos, Agustín; Muntané, Jordi; Jorquera, Francisco; Solà, Elsa; Hernández-Guerra, Manuel; Rojo, Miguel Ángel; Salmerón, Javier; Caballería, Llorenc; Diago, Moisés; Molina, Esther; Bataller, Ramón; Romero-Gómez, Manuel

    2018-05-01

    Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver diseases in Spain and the incidence is raising due to the outbreak of type 2 diabetes and obesity. This CPG suggests recommendation about diagnosis, mainly non-invasive biomarkers, and clinical management of this entity. Life-style modifications to achieve weight loss is the main target in the management of NAFLD. Low caloric Mediterranean diet and 200 minutes/week of aerobic exercise are encouraged. In non-responders patients with morbid obesity, bariatric surgery or metabolic endoscopy could be indicated. Pharmacological therapy is indicated in patients with NASH and fibrosis and non-responders to weight loss measures. NAFLD could influence liver transplantation, as a growing indication, the impact of steatosis in the graft viability, de novo NAFLD rate after OLT and a raised cardiovascular risk that modify the management of this entity. The current CPG was the result of the First Spanish NAFLD meeting in Seville. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  18. Fibrosis Assessment in Nonalcoholic Fatty Liver Disease (NAFLD) in 2016.

    PubMed

    Kaswala, Dharmesh H; Lai, Michelle; Afdhal, Nezam H

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver pathologies characterized by hepatic steatosis with a history of little to no alcohol consumption or secondary causes of hepatic steatosis. The prevalence of NAFLD is 20-25 % of the general population in the Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. The spectrum of disease ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis. Advanced fibrosis is the most significant predictor of mortality in NAFLD. It is crucial to assess for the presence and degree of hepatic fibrosis in order to make therapeutic decisions and predict clinical outcomes. Liver biopsy, the current gold standard to assess the liver fibrosis, has a number of drawbacks such as invasiveness, sampling error, cost, and inter-/intra-observer variability. There are currently available a number of noninvasive tests as an alternative to liver biopsy for fibrosis staging. These noninvasive fibrosis tests are increasingly used to rule out advanced fibrosis and help guide disease management. While these noninvasive tests perform relatively well for ruling out advanced fibrosis, they also have limitations. Understanding the strengths and limitations of liver biopsy and the noninvasive tests is necessary for deciding when to use the appropriate tests in the evaluation of patients with NAFLD.

  19. How Do Doctors Diagnose NAFLD and NASH?

    MedlinePlus

    ... NAFLD and NASH, such as overweight or obesity insulin resistance high levels of triglycerides or abnormal levels of ... NASH, such as an enlarged liver signs of insulin resistance such as darkened skin patches over your knuckles, ...

  20. The NAFLD Index: A Simple and Accurate Screening Tool for the Prediction of Non-Alcoholic Fatty Liver Disease.

    PubMed

    Ichino, Naohiro; Osakabe, Keisuke; Sugimoto, Keiko; Suzuki, Koji; Yamada, Hiroya; Takai, Hiroji; Sugiyama, Hiroko; Yukitake, Jun; Inoue, Takashi; Ohashi, Koji; Hata, Tadayoshi; Hamajima, Nobuyuki; Nishikawa, Toru; Hashimoto, Senju; Kawabe, Naoto; Yoshioka, Kentaro

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common debilitating condition in many industrialized countries that increases the risk of cardiovascular disease. The aim of this study was to derive a simple and accurate screening tool for the prediction of NAFLD in the Japanese population. A total of 945 participants, 279 men and 666 women living in Hokkaido, Japan, were enrolled among residents who attended a health check-up program from 2010 to 2014. Participants with an alcohol consumption > 20 g/day and/or a chronic liver disease, such as chronic hepatitis B, chronic hepatitis C or autoimmune hepatitis, were excluded from this study. Clinical and laboratory data were examined to identify predictive markers of NAFLD. A new predictive index for NAFLD, the NAFLD index, was constructed for men and for women. The NAFLD index for men = -15.5693+0.3264 [BMI] +0.0134 [triglycerides (mg/dl)], and for women = -31.4686+0.3683 [BMI] +2.5699 [albumin (g/dl)] +4.6740[ALT/AST] -0.0379 [HDL cholesterol (mg/dl)]. The AUROC of the NAFLD index for men and for women was 0.87(95% CI 0.88-1.60) and 0.90 (95% CI 0.66-1.02), respectively. The cut-off point of -5.28 for men predicted NAFLD with an accuracy of 82.8%. For women, the cut-off point of -7.65 predicted NAFLD with an accuracy of 87.7%. A new index for the non-invasive prediction of NAFLD, the NAFLD index, was constructed using available clinical and laboratory data. This index is a simple screening tool to predict the presence of NAFLD.

  1. Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution.

    PubMed

    Nozaki, Yuichi; Fujita, Koji; Wada, Koichiro; Yoneda, Masato; Shinohara, Yoshiyasu; Imajo, Kento; Ogawa, Yuji; Kessoku, Takaomi; Nakamuta, Makoto; Saito, Satoru; Masaki, Naohiko; Nagashima, Yoji; Terauchi, Yasuo; Nakajima, Atsushi

    2015-12-17

    Although many factors and molecules that are closely associated with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) have been reported, the role of endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) in the pathogenesis of NAFLD/NASH remains unclear. We therefore investigated the role of eNOS-derived NO in NAFLD pathogenesis using systemic eNOS-knockout mice fed a high-fat diet. eNOS-knockout and wild-type mice were fed a basal diet or a high-fat diet for 12 weeks. Lipid accumulation and inflammation were evaluated in the liver, and various factors that are closely associated with NAFLD/NASH and hepatic tissue blood flow were analyzed. Lipid accumulation and inflammation were more extensive in the liver and lipid accumulation was less extensive in the visceral fat tissue in eNOS-knockout mice, compared with wild-type mice, after 12 weeks of being fed a high-fat diet. While systemic insulin resistance was comparable between the eNOS-knockout and wild-type mice fed a high-fat diet, hepatic tissue blood flow was significantly suppressed in the eNOS-knockout mice, compared with the wild-type mice, in mice fed a high-fat diet. The microsomal triglyceride transfer protein activity was down-regulated in eNOS-knockout mice, compared with wild-type mice, in mice fed a high-fat diet. A deficiency of eNOS-derived NO may exacerbate the early-stage of NASH pathogenesis by changing the fat distribution in a mouse model via the regulation of hepatic tissue blood flow.

  2. Dietary fructose as a risk factor for non-alcoholic fatty liver disease (NAFLD).

    PubMed

    Alwahsh, Salamah Mohammad; Gebhardt, Rolf

    2017-04-01

    Glucose is a major energy source for the entire body, while fructose metabolism occurs mainly in the liver. Fructose consumption has increased over the last decade globally and is suspected to contribute to the increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is a manifestation of metabolic syndrome affecting about one-third of the population worldwide and has progressive pathological potential for liver cirrhosis and cancer through non-alcoholic steatohepatitis (NASH). Here we have reviewed the possible contribution of fructose to the pathophysiology of NAFLD. We critically summarize the current findings about several regulators, and their potential mechanisms, that have been studied in humans and animal models in response to fructose exposure. A novel hypothesis on fructose-dependent perturbation of liver regeneration and metabolism is advanced. Fructose intake could affect inflammatory and metabolic processes, liver function, gut microbiota, and portal endotoxin influx. The role of the brain in controlling fructose ingestion and the subsequent development of NAFLD is highlighted. Although the importance for fructose (over)consumption for NAFLD in humans is still debated and comprehensive intervention studies are invited, understanding of how fructose intake can favor these pathological processes is crucial for the development of appropriate noninvasive diagnostic and therapeutic approaches to detect and treat these metabolic effects. Still, lifestyle modification, to lessen the consumption of fructose-containing products, and physical exercise are major measures against NAFLD. Finally, promising drugs against fructose-induced insulin resistance and hepatic dysfunction that are emerging from studies in rodents are reviewed, but need further validation in human patients.

  3. Assessment of Diet and Physical Activity in Paediatric Non-Alcoholic Fatty Liver Disease Patients: A United Kingdom Case Control Study.

    PubMed

    Gibson, Philippa S; Lang, Sarah; Gilbert, Marianne; Kamat, Deepa; Bansal, Sanjay; Ford-Adams, Martha E; Desai, Ashish P; Dhawan, Anil; Fitzpatrick, Emer; Moore, J Bernadette; Hart, Kathryn H

    2015-11-26

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children, with prevalence rising alongside childhood obesity rates. This study aimed to characterise the habitual diet and activity behaviours of children with NAFLD compared to obese children without liver disease in the United Kingdom (UK). Twenty-four biopsy-proven paediatric NAFLD cases and eight obese controls without biochemical or radiological evidence of NAFLD completed a 24-h dietary recall, a Physical Activity Questionnaire (PAQ), a Dutch Eating Behavior Questionnaire (DEBQ) and a 7-day food and activity diary (FAD), in conjunction with wearing a pedometer. Groups were well matched for age and gender. Obese children had higher BMI z-scores (p = 0.006) and BMI centiles (p = 0.002) than participants with NAFLD. After adjusting for multiple hypotheses testing and controlling for differences in BMI, no differences in macro- or micronutrient intake were observed as assessed using either 24-h recall or 7-day FAD (p > 0.001). Under-reporting was prevalent (NAFLD 75%, Obese Control 87%: p = 0.15). Restrained eating behaviours were significantly higher in the NAFLD group (p = 0.005), who also recorded more steps per day than the obese controls (p = 0.01). In conclusion, this is the first study to assess dietary and activity patterns in a UK paediatric NAFLD population. Only a minority of cases and controls were meeting current dietary and physical activity recommendations. Our findings do not support development of specific dietary/ physical activity guidelines for children with NAFLD; promoting adherence with current general paediatric recommendations for health should remain the focus of clinical management.

  4. Non-Alcoholic Fatty Liver Disease (NAFLD): new challenge for general practitioners and important burden for health authorities?

    PubMed

    Ahmed, Mohamed H; Abu, Emmanuel O; Byrne, Christopher D

    2010-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of hepatic dysfunction encountered in general practice. A large proportion of individuals with type 2 diabetes and the metabolic syndrome develop NAFLD. NAFLD is associated with severe insulin resistance and increased risk of cardiovascular disease and can progress to non-alcoholic steato-hepatitis, liver cirrhosis and cancer. Currently the only known effective treatments for NAFLD are lifestyle changes including stable weight loss and a diet low in calories. General practitioners will increasingly play a key role in dealing with this evolving but serious epidemic of NAFLD and associated metabolic complications. However, success will depend on the appropriate systems and mechanisms being in place in primary care and the proper motivation, support and education of the patient. This review provides the primary care physician with: (a) a step-by step guide of how to identify NAFLD, (b) information to exclude common other causes of liver fat accumulation and (c) additional insight into relationships between NAFLD and other conditions such as obesity, cardiovascular disease and type 2 diabetes. Copyright © 2010 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  5. Pharmacological and antioxidant actions of garlic and.or onion in non-alcoholic fatty liver disease (NAFLD) in rats.

    PubMed

    El-Din, Sayed H Seif; Sabra, Abdel-Nasser A; Hammam, Olfat A; Ebeid, Fatma A; El-Lakkany, Naglaa M

    2014-08-01

    Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of fat-induced liver injury, ranging from mild steatosis to cirrhosis and liver failure. This study investigates the hepatoprotective properties of garlic and onion in NAFLD rat model. Ninety male Sprague-Dawley rats were randomly divided into 9 groups; normal (I), NAFLD induced with high fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with garlic (IV, V), onion (VI, VII) or the combined garlic+onion (VIII, IX) respectively. A NAFLD rat model was established by feeding the animals with a high-fat diet for 12 wk. These animals were then treated with garlic or/and onion or vehicle for 8 wk (weeks 13-20) and then killed to obtain serum samples and liver tissues. Liver histology, lipids, parameters of oxidative stress, TNF-α and TGF-β were measured. The liver in NAFLD-HFD showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration. Serum levels of ALT, AST, ALP, leptin, cholesterol, triglycerides, TNF-α, TGF-β and hepatic MDA' were significantly increased (P < 0.05) compared with normal group. This was accompanied with reduction of hepatic GSH, GR, GPx, GST, SOD and serum adiponectin. These changes were to a less degree in NAFLD-RD group. Combined administration of garlic+onion produced a better and significant decrease in liver steatosis, serum liver enzymes, oxidative markers and lipid peroxidation versus each one alone. In the same time, NAFLD-induced inflammation was also mitigated via reduction of TNF-α and TGF-β. In addition, these results were better in the group IX versus group VIII.

  6. Non-Alcoholic Fatty Liver Disease (NAFLD) in children and adolescents with Prader-Willi Syndrome (PWS).

    PubMed

    Fintini, D; Inzaghi, E; Colajacomo, M; Bocchini, S; Grugni, G; Brufani, C; Cappa, M; Nobili, V; Cianfarani, S; Crinò, A

    2016-06-01

    We tested the hypothesis that patients with Prader-Willi syndrome (PWS) may be at lower risk of developing non-alcoholic fatty liver disease (NAFLD) because of a higher insulin sensitivity. Twenty-one PWS patients and 42 control subjects closely similar for age, gender, pubertal stage and body mass index (CNT), were studied. Metabolic profile and body composition were assessed. NAFLD was established by a validated method of US grading (range from G0 to G3). PWS patients showed a significantly better metabolic profile (lower waist circumference, fasting glucose levels, HOMA-IR, cholesterol, transaminase levels and trunk fat mass/fat mass ratio). Furthermore, NAFLD G1stage was significantly more frequent in PWS subjects (P < 0.05), whereas G2 stage was significantly more frequent in control patients (P < 0.05). NAFLD grading seems to correlate with body composition in PWS, also after adjustment for sex and GH treatment. To our knowledge, this is the first report suggesting a reduced risk of NAFLD in PWS children. © 2015 World Obesity.

  7. Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism

    PubMed Central

    Jegatheesan, Prasanthi; De Bandt, Jean-Pascal

    2017-01-01

    Among various factors, such as an unhealthy diet or a sedentarity lifestyle, excessive fructose consumption is known to favor nonalcoholic fatty liver disease (NAFLD), as fructose is both a substrate and an inducer of hepatic de novo lipogenesis. The present review presents some well-established mechanisms and new clues to better understand the pathophysiology of fructose-induced NAFLD. Beyond its lipogenic effect, fructose intake is also at the onset of hepatic inflammation and cellular stress, such as oxidative and endoplasmic stress, that are key factors contributing to the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Beyond its hepatic effects, this carbohydrate may exert direct and indirect effects at the peripheral level. Excessive fructose consumption is associated, for example, with the release by the liver of several key mediators leading to alterations in the communication between the liver and the gut, muscles, and adipose tissue and to disease aggravation. These multifaceted aspects of fructose properties are in part specific to fructose, but are also shared in part with sucrose and glucose present in energy–dense beverages and foods. All these aspects must be taken into account in the development of new therapeutic strategies and thereby to better prevent NAFLD. PMID:28273805

  8. Markers of activated inflammatory cells correlate with severity of liver damage in children with nonalcoholic fatty liver disease.

    PubMed

    De Vito, Rita; Alisi, Anna; Masotti, Andrea; Ceccarelli, Sara; Panera, Nadia; Citti, Arianna; Salata, Michele; Valenti, Luca; Feldstein, Ariel E; Nobili, Valerio

    2012-07-01

    Concomitantly to the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in children. NAFLD encompasses a spectrum of histological damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), with possible progression to cirrhosis. There is growing evidence that the immune system plays a pivotal role in the initiation and progression to NASH but the cellular nature of the hepatic inflammation is still unknown. The present study includes 34 children with biopsy-proven NAFLD. Liver damage was evaluated by the NAFLD activity score (NAS), and the inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3 and CD163 which are markers of leukocytes, T cells and activated Kupffer cells/macrophages, respectively. Our results have shown that CD45+ (P<0.0001) and CD163+ (P<0.0001) cells were markedly increased in children with severe histological activity (NAS≥5) compared to children with lower activity (NAS<5), whereas CD3+ cells were significantly lower (P<0.01) in children with severe histological activity. There was a significant association between the numbers of CD45+, CD3+ and CD163+ cells, regarding both the portal tract and liver lobule, and the severity of steatosis, ballooning and fibrosis (P<0.01). These data suggest that the severity and composition of the inflammatory infiltrate correlate with steatosis and the severity of disease in children with NAFLD. Moreover, a decrease in CD3+ cells may be involved in the pathogenesis of liver damage. Future studies should evaluate whether it can predict the progression of liver disease independently of established histological scores.

  9. The role of intestinal microbiota in the pathogenesis of NAFLD: starting points for intervention

    PubMed Central

    Vespasiani-Gentilucci, Umberto; Picardi, Antonio

    2016-01-01

    In recent years, close links between intestinal microbiota and host metabolism have been recognized. Intestinal bacteria can participate in the extraction of calories from food, and circulation of bacterial products, in particular lipopolysaccharides (LPS), is responsible for the “metabolic endotoxemia”, which contributes to insulin resistance and its complications, such as non-alcoholic fatty liver disease (NAFLD). Indeed, qualitative and quantitative intestinal dysbiotic changes have been clearly documented in NAFLD patients, and several mechanisms by which the intestinal microbiota can directly promote liver fat deposition, inflammation and fibrosis have also been described. Consistently, although with some differences concerning type and proportion of results, experimental and clinical studies are quite concordant in demonstrating beneficial effects of probiotic and/or prebiotic therapy in NAFLD. Although some physiopathological bases have been produced, major doubts still remain concerning how and when to intervene. Indeed, most of the available works were performed with mixtures of probiotics and/or prebiotics, and a baseline assessment of dysbiosis aimed at selecting the best candidates for treatment and predicting response has not been performed in any of the clinical studies in NAFLD. While future research is expected to solve these issues, the particularly favorable safety profile suggests that probiotic/prebiotic therapy could already be “tested” in NAFLD patients on an individual basis, at least once all the measures recommended by the latest guidelines have failed. PMID:29765460

  10. [Effect of Shugan Jianpi Recipe on LXRα/FAS signaling pathway mediated hepatocyte fatty deposits in NAFLD rats].

    PubMed

    Gong, Xiang-Wen; Yang-Qin-He; Yan, Hai-Zhen; Zhang, Yu-Pei; Huang, Jin; Xu, Yong-Jian; Zhang, Jin-Wen; Lin, Chun-Mei

    2014-12-01

    To explore the effect of Shugan Jianpi Recipe (SJR) on LXRα/FAS signaling pathway mediated hepatocyte fatty deposits in nonalcoholic fatty liver disease (NAFLD) rats. Totally 75 SPF grade male SD rats were randomly divided into 5 groups, i.e., the normal control group, the model group, the Shugan Recipe (SR) treatment groups, the Jianpi Recipe (JR) treatment group, and the SJR group. Except rats in the normal control group, the NAFLD rat model was duplicated using high fat diet (HFD). SR (Chaihu Shugan Powder) was administered to rats in the SR group. JR (Shenlin Baizhu Powder) was administered to rats in the JR group. SJR (Chaihu Shugan Powder plus Shenlin Baizhu Powder) was administered to rats in the SJR group. Changes of liver fat were analyzed using automatic biochemical analyzer. Liver cells were separated by low-speed centrifugation. Their activities and purities were identify using Typan blue and flow cytometry (FCM). Expression levels of LXRα and FAS mRNA in hepatocytes detected by Real-time quantitative PCR. Expression levels of LXRα and FAS protein were detected by Western blot. (1) Pathological results showed in the model group, hepatocytes were swollen with nucleus locating at the cell edge after oil red O staining; unequal sized small vacuoles could be seen inside cytoplasm. Some small vacuoles merged big vacuoles. All these indi- cated a NAFLD rat model was successfully established by high fat diet. Pathological structural changes could be impaired to some degree in all medicated groups, especially in the SR group. (2) Compared with the normal control group, expression levels of LXRα and FAS genes and proteins obviously increased in the model group (P < 0.01). Compared with the model group, their expression levels were obviously down-regulated in the JR group and the SR group (P < 0.01, P < 0.05). LXRα/FAS signaling pathway was an important signaling pathway for mediating lipid metabolism disorders of NAFLD rats. SJR could make hepatocyte fatty

  11. [Non-alcoholic fatty liver disease (NAFLD) in patients with metabolic syndrome and type 2 diabetes mellitus. Pathomechanism, new diagnostic markers].

    PubMed

    Kieć-Wilk, Beata; Klupa, Tomasz; Dembińska-Kieć, Aldona

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a complex of a wide spectrum of liver pathology--from steatosis alone, to cirrhosis and liver cancer. The pathogenic concept of NAFLD covers overnutrition with fatty acids, underactivity. Insulin resistance is believed to play the main role in this process. NAFLD is mostly related to visceral adiposity, metabolic syndrome and type 2 diabetes melitus. The presented work is a review of in vitro and in vivo modern studies, as well as clinical observations on molecular mechanisms leading to development and progress of NAFLD. Up till today their is no treatment od NAFLD, and this pathology is not benign--it may lead to patients' death in 10 years. The clinical approach to NAFLD is prevention of it's development. The manuscript is a review of new biochemical markers allowing for early detection of metabolic disorders leading to NAFLD development, thus to sufficient prevention of this pathology in patients.

  12. The severity of NAFLD is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota

    PubMed Central

    Boursier, Jérôme; Mueller, Olaf; Barret, Matthieu; Machado, Mariana; Fizanne, Lionel; Araujo-Perez, Felix; Guy, Cynthia D.; Seed, Patrick C.; Rawls, John F.; David, Lawrence A.; Hunault, Gilles; Oberti, Frédéric; Calès, Paul; Diehl, Anna Mae

    2016-01-01

    Background & aims Several animal studies have emphasized the role of gut microbiota in non-alcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remains scarce in the literature, especially studies including the whole spectrum of NAFLD lesions. We aimed to evaluate the association between gut dysbiosis and severe NAFLD lesions, i.e. non-alcoholic steatohepatitis (NASH) and fibrosis, in a well-characterized population of adult NAFLD. Methods 57 patients with biopsy-proven NAFLD were enrolled. The taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Results 30 patients had F0/1 fibrosis stage at liver biopsy (10 with NASH), and 27 patients had significant F≥2 fibrosis (25 with NASH). Bacteroides abundance was significantly increased in NASH and F≥2 patients, whereas Prevotella abundance was decreased. Ruminococcus abundance was significantly higher in F≥2 patients. By multivariate analysis, Bacteroides abundance was independently associated with NASH and Ruminococcus with F≥2 fibrosis. Stratification according to the abundance of these 2 bacteria generated 3 patient subgroups with increasing severity of NAFLD lesions. Based on imputed metagenomic profiles, KEGG pathways significantly related to NASH and fibrosis F≥2 were mostly related to carbohydrate, lipid, and amino acid metabolism. Conclusion NAFLD severity associates with gut dysbiosis and a shift in metabolic function of the gut microbiota. We identified Bacteroides as independently associated with NASH and Ruminococcus with significant fibrosis. Thus, gut microbiota analysis adds information to classical predictors of NAFLD severity and suggests novel metabolic targets for pre/probiotics therapies. PMID:26600078

  13. Molecular signature of adipose tissue in patients with both Non-Alcoholic Fatty Liver Disease (NAFLD) and Polycystic Ovarian Syndrome (PCOS)

    PubMed Central

    2013-01-01

    Background Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only. Methods We included patients with biopsy-proven NAFLD and PCOS (N = 12) and BMI-matched biopsy-proven NAFLD patients without PCOS (N = 12). Expression levels of individual mRNAs and soluble serum biomarkers were compared by non-parametric Mann–Whitney test. The analysis also included Spearman rank correlation tests and multiple regression analysis. For co-correlated genes, the factor analysis was performed. Results The total serum levels of apoptotic biomarker M30 were significantly elevated in PCOS patients with liver steatosis as compared to non-PCOS NAFLD controls (P < 0.02), pointing that androgen-dependent proapoptotic PCOS environment that may directly contribute to NAFLD progression in these patients. Similarly, hyperandrogenism may explain the observed PCOS-specific decrease (P < 0.04) in adipose LDLR mRNA expression that may be connected to the proneness of PCOS patients to NAFLD. The levels of mRNA encoding angiogenesis-associated GSK-3B interacting protein ninein were also significantly increased in the adipose tissue of NAFLD patients with PCOS (P < 0.007). Furthermore, the levels of resistin positively correlated with expression levels of LDLR and prothrombin time (PT). Conclusion An androgen-dependent proapoptotic PCOS environment may directly contribute to NAFLD progression in these patients. Hyperandrogenism may explain an observed decrease in adipose LDLR mRNA expression. An inflammation-associated increase in the release of resistin into circulation might contribute

  14. Molecular signature of adipose tissue in patients with both non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS).

    PubMed

    Baranova, Ancha; Tran, Thuy Phuong; Afendy, Arian; Wang, Lei; Shamsaddini, Amirhossein; Mehta, Rohini; Chandhoke, Vikas; Birerdinc, Aybike; Younossi, Zobair M

    2013-05-31

    Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only. We included patients with biopsy-proven NAFLD and PCOS (N = 12) and BMI-matched biopsy-proven NAFLD patients without PCOS (N = 12). Expression levels of individual mRNAs and soluble serum biomarkers were compared by non-parametric Mann-Whitney test. The analysis also included Spearman rank correlation tests and multiple regression analysis. For co-correlated genes, the factor analysis was performed. The total serum levels of apoptotic biomarker M30 were significantly elevated in PCOS patients with liver steatosis as compared to non-PCOS NAFLD controls (P < 0.02), pointing that androgen-dependent proapoptotic PCOS environment that may directly contribute to NAFLD progression in these patients. Similarly, hyperandrogenism may explain the observed PCOS-specific decrease (P < 0.04) in adipose LDLR mRNA expression that may be connected to the proneness of PCOS patients to NAFLD. The levels of mRNA encoding angiogenesis-associated GSK-3B interacting protein ninein were also significantly increased in the adipose tissue of NAFLD patients with PCOS (P < 0.007). Furthermore, the levels of resistin positively correlated with expression levels of LDLR and prothrombin time (PT). An androgen-dependent proapoptotic PCOS environment may directly contribute to NAFLD progression in these patients. Hyperandrogenism may explain an observed decrease in adipose LDLR mRNA expression. An inflammation-associated increase in the release of resistin into circulation might contribute to the prothrombotic state observed

  15. Genetic Predisposition in NAFLD and NASH: Impact on Severity of Liver Disease and Response to Treatment

    PubMed Central

    Dongiovanni, Paola; Anstee, Quentin M; Valenti, Luca

    2013-01-01

    Liver fat deposition related to systemic insulin resistance defines non-alcoholic fatty liver disease (NAFLD) which, when associated with oxidative hepatocellular damage, inflammation, and activation of fibrogenesis, i.e. non-alcoholic steatohepatitis (NASH), can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease and the leading cause of altered liver enzymes in Western countries. Epidemiological, familial, and twin studies provide evidence for an element of heritability of NAFLD. Genetic modifiers of disease severity and progression have been identified through genome-wide association studies. These include the Patatin-like phosholipase domain-containing 3 (PNPLA3) gene variant I148M as a major determinant of inter-individual and ethnicity-related differences in hepatic fat content independent of insulin resistance and serum lipid concentration. Association studies confirm that the I148M polymorphism is also a strong modifier of NASH and progressive hepatic injury. Furthermore, a few large multicentre case-control studies have demonstrated a role for genetic variants implicated in insulin signalling, oxidative stress, and fibrogenesis in the progression of NAFLD towards fibrosing NASH, and confirm that hepatocellular fat accumulation and insulin resistance are key operative mechanisms closely involved in the progression of liver damage. It is now important to explore the molecular mechanisms underlying these associations between gene variants and progressive liver disease, and to evaluate their impact on the response to available therapies. It is hoped that this knowledge will offer further insights into pathogenesis, suggest novel therapeutic targets, and could help guide physicians towards individualised therapy that improves clinical outcome. PMID:23394097

  16. Reduced circulating levels of sTWEAK are associated with NAFLD and may affect hepatocyte triglyceride accumulation.

    PubMed

    Lozano-Bartolomé, J; Llauradó, G; Rodriguez, M M; Fernandez-Real, J M; Garcia-Fontgivell, J F; Puig, J; Maymó-Masip, E; Vendrell, J; Chacón, M R

    2016-09-01

    Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is strongly associated with obesity, dyslipidaemia and altered glucose regulation. Previous data demonstrated that low circulating levels of tumour necrosis factor weak inducer of apoptosis (sTWEAK) were associated with obesity, diabetes and insulin resistance, all traits associated with an increased risk of NALFD. Circulating sTWEAK levels are expected to be reduced in the presence of NAFLD. We aimed to explore the relationship between NAFLD and circulating sTWEAK levels in obese patients, and to evaluate the effect of sTWEAK on hepatocyte triglyceride accumulation.Design setting and patients:This is an observational case-control study performed in n=112 severely obese patients evaluated for NAFLD by abdominal ultrasound and n=32 non-obese patients without steatosis. Serum sTWEAK concentrations were measured by ELISA. Multivariable analyses were performed to determine the independent predictors of NAFLD. We analysed TWEAK and Fn14 protein expression in liver biopsies by western blotting and immunohistochemistry. An immortalized primary human hepatocyte cell line (HHL) was used to evaluate the effect of sTWEAK on triglyceride accumulation. We observed a reduction in serum circulating sTWEAK concentrations with the presence of liver steatosis. On multivariable analysis, lower sTWEAK concentrations were independently associated with the presence of NAFLD (odds ratio (OR)=0.023; 95% confidence interval: 0.001-0.579; P<0.022). In human hepatocytes, sTWEAK administration reduced fat accumulation as demonstrated by the reduction in palmitic acid-induced accumulation of triglyceride and the decreased expression of cluster of differentiation 36 (CD36) and perilipin 1 and 2 (PLIN1 and PLIN2) genes. Decreased sTWEAK concentrations are independently associated with the presence of NAFLD. This is concordant with the observation that TWEAK reduces lipid accumulation in human

  17. Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD).

    PubMed

    Notarnicola, Maria; Caruso, Maria Gabriella; Tutino, Valeria; Bonfiglio, Caterina; Cozzolongo, Raffaele; Giannuzzi, Vito; De Nunzio, Valentina; De Leonardis, Giampiero; Abbrescia, Daniela I; Franco, Isabella; Intini, Vincenza; Mirizzi, Antonella; Osella, Alberto R

    2017-08-23

    The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage. This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD. Diagnosis of liver steatosis was performed by using vibration-controlled elastography implemented on FibroScan. Fatty acids, extracted from phospholipids of erythrocyte membranes, were quantified by gas chromatography method. The subjects with severe NAFLD showed a significant decrease of the ratio of stearic acid to oleic acid (saturation index, SI) compared to controls, 1.281 ± 0.31 vs 1.5 ± 0.29, respectively. Low levels of SI in red blood cell membranes, inversely associated with degree of liver damage, suggest that an impairment of circulating cell membrane structure can reflect modifications that take place in the liver. Subjects with severe NAFLDalso showed higher levels of elongase 5 enzymatic activity, evaluated as vaccenic acid to palmitoleic acid ratio. Starting from these evidences, our findings show the importance of lipidomic approach in the diagnosis and the staging of NAFLD.

  18. Knowledge-based identification of soluble biomarkers: hepatic fibrosis in NAFLD as an example.

    PubMed

    Page, Sandra; Birerdinc, Aybike; Estep, Michael; Stepanova, Maria; Afendy, Arian; Petricoin, Emanuel; Younossi, Zobair; Chandhoke, Vikas; Baranova, Ancha

    2013-01-01

    The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.

  19. Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example

    PubMed Central

    Page, Sandra; Birerdinc, Aybike; Estep, Michael; Stepanova, Maria; Afendy, Arian; Petricoin, Emanuel; Younossi, Zobair; Chandhoke, Vikas; Baranova, Ancha

    2013-01-01

    The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases. PMID:23405244

  20. Lack of NLRP3-inflammasome leads to gut-liver axis derangement, gut dysbiosis and a worsened phenotype in a mouse model of NAFLD.

    PubMed

    Pierantonelli, Irene; Rychlicki, Chiara; Agostinelli, Laura; Giordano, Debora Maria; Gaggini, Melania; Fraumene, Cristina; Saponaro, Chiara; Manghina, Valeria; Sartini, Loris; Mingarelli, Eleonora; Pinto, Claudio; Buzzigoli, Emma; Trozzi, Luciano; Giordano, Antonio; Marzioni, Marco; Minicis, Samuele De; Uzzau, Sergio; Cinti, Saverio; Gastaldelli, Amalia; Svegliati-Baroni, Gianluca

    2017-09-22

    Non-Alcoholic Fatty Liver Disease (NAFLD) represents the most common form of chronic liver injury and can progress to cirrhosis and hepatocellular carcinoma. A "multi-hit" theory, involving high fat diet and signals from the gut-liver axis, has been hypothesized. The role of the NLRP3-inflammasome, which senses dangerous signals, is controversial. Nlrp3 -/- and wild-type mice were fed a Western-lifestyle diet with fructose in drinking water (HFHC) or a chow diet. Nlrp3 -/- -HFHC showed higher hepatic expression of PPAR γ2 (that regulates lipid uptake and storage) and triglyceride content, histological score of liver injury and greater adipose tissue inflammation. In Nlrp3 -/- -HFHC, dysregulation of gut immune response with impaired antimicrobial peptides expression, increased intestinal permeability and the occurrence of a dysbiotic microbiota led to bacterial translocation, associated with higher hepatic expression of TLR4 (an LPS receptor) and TLR9 (a receptor for double-stranded bacterial DNA). After antibiotic treatment, gram-negative species and bacterial translocation were reduced, and adverse effects restored both in liver and adipose tissue. In conclusion, the combination of a Western-lifestyle diet with innate immune dysfunction leads to NAFLD progression, mediated at least in part by dysbiosis and bacterial translocation, thus identifying new specific targets for NAFLD therapy.

  1. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD.

    PubMed

    Permutt, Z; Le, T-A; Peterson, M R; Seki, E; Brenner, D A; Sirlin, C; Loomba, R

    2012-07-01

    Conventional magnetic resonance imaging (MRI) techniques that measure hepatic steatosis are limited by T1 bias, T(2)* decay and multi-frequency signal-interference effects of protons in fat. Newer MR techniques such as the proton density-fat fraction (PDFF) that correct for these factors have not been specifically compared to liver biopsy in adult patients with non-alcoholic fatty liver disease (NAFLD). To examine the association between MRI-determined PDFF and histology-determined steatosis grade, and their association with fibrosis. A total of 51 adult patients with biopsy-confirmed NAFLD underwent metabolic-biochemical profiling, MRI-determined PDFF measurement of hepatic steatosis and liver biopsy assessment according to NASH-CRN histological scoring system. The average MRI-determined PDFF increased significantly with increasing histology-determined steatosis grade: 8.9% at grade-1, 16.3% at grade-2, and 25.0% at grade-3 with P ≤ 0.0001 (correlation: r(2) = 0.56, P < 0.0001). Patients with stage-4 fibrosis, when compared with patients with stage 0-3 fibrosis, had significantly lower hepatic steatosis by both MRI-determined PDFF (7.6% vs. 17.8%, P < 0.005) and histology-determined steatosis grade (1.4 vs. 2.2, P < 0.05). NAFLD patients with grade 1 steatosis were more likely to have characteristics of advanced liver disease including higher average AST:ALT (0.87 vs. 0.60, P < 0.02), GGT (140 vs. 67, P < 0.01), and INR (1.06 vs. 0.99, P < 0.01), higher stage of fibrosis and hepatocellular ballooning. MRI-determined proton density-fat fraction correlates with histology-determined steatosis grade in adults with NAFLD. Steatosis is non-linearly related to fibrosis progression. In patients with NAFLD, a low amount of hepatic steatosis on imaging does not necessarily indicate mild disease. © 2012 Blackwell Publishing Ltd.

  2. Assessment of Portal Venous and Hepatic Artery Haemodynamic Variation in Non-Alcoholic Fatty Liver Disease (NAFLD) Patients.

    PubMed

    Balasubramanian, Padhmini; Boopathy, Vinoth; Govindasamy, Ezhumalai; Venkatesh, Basavaiya Prabhu

    2016-08-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) has various spectrums of liver diseases like isolated fatty liver, steatohepatitis and cirrhosis usually progressing in a linear fashion. In this process they are known to cause certain haemodynamic changes in the portal flow and hepatic artery flow. The aim of the study was to study these haemodynamic changes in patients with NAFLD and to correlate it with the disease severity. Ninety patients diagnosed to have NAFLD based on ultrasound abdomen (30 each in grade1, grade2 and grade3 NAFLD) and 30 controls (Normal liver on ultrasound abdomen) were subjected to portal vein and hepatic artery Doppler study. Peak maximum velocity (Vmax), Peak minimum velocity (Vmin), Mean flow velocity (MFV), and Vein pulsality index (VPI) of the portal vein and hepatic artery resistivity index (HARI) of the hepatic artery were the doppler parameters which were assessed. Liver span was also assessed both for the fatty liver and controls. The mean Vmax, Vmin, MFV and VPI of the portal vein in patients with NAFLD was 12.23±1.74cm/sec, 9.31±1.45cm/sec, 10.76±1.48cm/sec, and 0.24±0.04 as compared to 14.05±2.43cm/sec, 10.01±2.27cm/sec, 12.23±2.47cm/sec, 0.3±0.08 in controls respectively. All these differences were statistically significant except for Vmin. The Mean HARI in patients with fatty liver was 0.65±0.06 when compared to controls of 0.75±0.06 (p=0.001). HARI (r-value of -0.517) had a better negative correlation followed by VPI (r-value of -0.44) and Vmax (r-value of -0.293) with the severity of NAFLD. MFV had a very weak negative correlation (r-value of -0.182) with the severity of NAFLD. The Vmax, MFV, VPI and HARI were significantly less when compared to controls suggesting a reduced portal flow and an increased hepatic arterial flow in patients with NAFLD. Among the parameters, HARI correlated better with the severity of NAFLD followed by VPI.

  3. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice.

    PubMed

    Ideta, Takayasu; Shirakami, Yohei; Miyazaki, Tsuneyuki; Kochi, Takahiro; Sakai, Hiroyasu; Moriwaki, Hisataka; Shimizu, Masahito

    2015-12-08

    Non-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome, is increasingly a major cause of hepatic disorder. Dipeptidyl peptidase (DPP)-4 inhibitors, anti-diabetic agents, are expected to be effective for the treatment of NAFLD. In the present study, we established a novel NAFLD model mouse using monosodium glutamate (MSG) and a high-fat diet (HFD) and investigated the effects of a DPP-4 inhibitor, teneligliptin, on the progression of NAFLD. Male MSG/HFD-treated mice were divided into two groups, one of which received teneligliptin in drinking water. Administration of MSG and HFD caused mice to develop severe fatty changes in the liver, but teneligliptin treatment improved hepatic steatosis and inflammation, as evaluated by the NAFLD activity score. Serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased in teneligliptin-treated mice (p < 0.05). Hepatic mRNA levels of the genes involved in de novo lipogenesis were significantly downregulated by teneligliptin (p < 0.05). Moreover, teneligliptin increased hepatic expression levels of phosphorylated AMP-activated protein kinase (AMPK) protein. These findings suggest that teneligliptin attenuates lipogenesis in the liver by activating AMPK and downregulating the expression of genes involved in lipogenesis. DPP-4 inhibitors may be effective for the treatment of NAFLD and may be able to prevent its progression to non-alcoholic steatohepatitis.

  4. NAFLD and Atherosclerosis Are Prevented by a Natural Dietary Supplement Containing Curcumin, Silymarin, Guggul, Chlorogenic Acid and Inulin in Mice Fed a High-Fat Diet.

    PubMed

    Amato, Antonella; Caldara, Gaetano-Felice; Nuzzo, Domenico; Baldassano, Sara; Picone, Pasquale; Rizzo, Manfredi; Mulè, Flavia; Di Carlo, Marta

    2017-05-13

    Non-alcoholic fatty liver disease (NAFLD) confers an increased risk of cardiovascular diseases. NAFDL is associated with atherogenic dyslipidemia, inflammation and renin-angiotensin system (RAS) imbalance, which in turn lead to atherosclerotic lesions. In the present study, the impact of a natural dietary supplement (NDS) containing Curcuma longa , silymarin, guggul, chlorogenic acid and inulin on NAFLD and atherosclerosis was evaluated, and the mechanism of action was examined. C57BL/6 mice were fed an HFD for 16 weeks; half of the mice were simultaneously treated with a daily oral administration (os) of the NDS. NAFLD and atherogenic lesions in aorta and carotid artery (histological analysis), hepatic expression of genes involved in the NAFLD (PCR array), hepatic angiotensinogen (AGT) and AT₁R mRNA expression (real-time PCR) and plasma angiotensin (ANG)-II levels (ELISA) were evaluated. In the NDS group, steatosis, aortic lesions or carotid artery thickening was not observed. PCR array showed upregulation of some genes involved in lipid metabolism and anti-inflammatory activity (Cpt2, Ifng) and downregulation of some genes involved in pro-inflammatory response and in free fatty acid up-take (Fabp5, Socs3). Hepatic AGT, AT₁R mRNA and ANG II plasma levels were significantly lower with respect to the untreated-group. Furthermore, NDS inhibited the dyslipidemia observed in the untreated animals. Altogether, these results suggest that NDS prevents NAFLD and atherogenesis by modulating the expression of different genes involved in NAFLD and avoiding RAS imbalance.

  5. Acetyl-CoA Carboxylase Inhibition Reverses NAFLD and Hepatic Insulin Resistance but Promotes Hypertriglyceridemia in Rodents.

    PubMed

    Goedeke, Leigh; Bates, Jamie; Vatner, Daniel F; Perry, Rachel J; Wang, Ting; Ramirez, Ricardo; Li, Li; Ellis, Matthew W; Zhang, Dongyan; Wong, Kari E; Beysen, Carine; Cline, Gary W; Ray, Adrian S; Shulman, Gerald I

    2018-05-23

    Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) via simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation. However, the effects of ACC inhibition on hepatic mitochondrial oxidation, anaplerosis, and ketogenesis in vivo are unknown. Here, we evaluated the impact of a novel liver-directed allosteric inhibitor of ACC1 and ACC2 (Compound 1) on these parameters, as well as glucose and lipid metabolism, in control and diet-induced rodent models of NAFLD. Oral administration of Compound 1 preferentially inhibited ACC enzymatic activity in the liver, reduced hepatic malonyl-CoA levels and enhanced hepatic ketogenesis by 50%. Furthermore, administration for 6 days to high-fructose fed rats resulted in a 20% reduction in hepatic de novo lipogenesis. Importantly, long-term treatment (21 days) significantly reduced high-fat sucrose diet (HFSD)-induced hepatic steatosis, PKCε activation and hepatic insulin resistance. ACCi treatment was associated with a significant increase in plasma triglycerides (∼30 to 130%, depending on length of fasting). ACCi-mediated hypertriglyceridemia could be attributed to a ∼15% increase in hepatic VLDL production and ∼20% reduction in triglyceride clearance by lipoprotein lipase (LPL) (P ≤ 0.05). At the molecular level, these changes were associated with increases in LXR/SREBP1 and decreases in PPARα target activation and could be reversed with fenofibrate co-treatment in a high-fat diet mouse model. Collectively, these studies warrant further investigation into the therapeutic utility of liver-directed ACC inhibition for the treatment of NAFLD and hepatic insulin resistance. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  6. How healthy are the "Healthy volunteers"? Penetrance of NAFLD in the biomedical research volunteer pool.

    PubMed

    Takyar, Varun; Nath, Anand; Beri, Andrea; Gharib, Ahmed M; Rotman, Yaron

    2017-09-01

    Healthy volunteers are crucial for biomedical research. Inadvertent inclusion of subjects with nonalcoholic fatty liver disease (NAFLD) as controls can compromise study validity and subject safety. Given the rising prevalence of NAFLD in the general population, we sought to identify its prevalence and potential impact in volunteers for clinical trials. We conducted a cross-sectional study of subjects who were classified as healthy volunteers between 2011 and 2015 and had no known liver disease. Subjects were classified as presumed NAFLD (pNF; alanine aminotransferase [ALT] level ≥ 20 for women or ≥ 31 for men and body mass index [BMI] > 25 kg/m 2 ), healthy non-NAFLD controls (normal ALT and BMI), or indeterminate. A total of 3160 subjects participated as healthy volunteers in 149 clinical trials (1-29 trials per subject); 1732 of these subjects (55%) had a BMI > 25 kg/m 2 and 1382 (44%) had abnormal ALT. pNF was present in 881 subjects (27.9%), and these subjects were older than healthy control subjects and had higher triglycerides, low-density lipoprotein cholesterol, and HbA1c and lower high-density lipoprotein cholesterol (P < 0.001 for all). The 149 trials included 101 non-interventional, 33 interventional, and 15 vaccine trials. The impact on study validity of recruiting NAFLD subjects as controls was estimated as likely, probable, and unlikely in 10, 41, and 98 trials, respectively. The proportion of pNF subjects (28%-29%) did not differ by impact. Only 14% of trials used both BMI and ALT for screening. ALT cutoffs for screening were based on local reference values. Grade 3-4 ALT elevations during the study period were rare but more common in pNF subjects than in healthy control subjects (4 versus 1). NAFLD is common and often overlooked in volunteers for clinical trials, despite its potential impact on subject safety and validity of study findings. Increased awareness of NAFLD prevalence and stricter ALT cutoffs may ameliorate

  7. Non-alcoholic fatty liver disease (NAFLD) potentiates autoimmune hepatitis in the CYP2D6 mouse model.

    PubMed

    Müller, Peter; Messmer, Marie; Bayer, Monika; Pfeilschifter, Josef M; Hintermann, Edith; Christen, Urs

    2016-05-01

    Non-alcoholic fatty liver disease (NAFLD) and its more severe development non-alcoholic steatohepatitis (NASH) are increasing worldwide. In particular NASH, which is characterized by an active hepatic inflammation, has often severe consequences including progressive fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). Here we investigated how metabolic liver injury is influencing the pathogenesis of autoimmune hepatitis (AIH). We used the CYP2D6 mouse model in which wild type C57BL/6 mice are infected with an Adenovirus expressing the major liver autoantigen cytochrome P450 2D6 (CYP2D6). Such mice display several features of human AIH, including interface hepatitis, formation of LKM-1 antibodies and CYP2D6-specific T cells, as well as hepatic fibrosis. NAFLD was induced with a high-fat diet (HFD). We found that pre-existing NAFLD potentiates the severity of AIH. Mice fed for 12 weeks with a HFD displayed increased cellular infiltration of the liver, enhanced hepatic fibrosis and elevated numbers of liver autoantigen-specific T cells. Our data suggest that a pre-existing metabolic liver injury constitutes an additional risk for the severity of an autoimmune condition of the liver, such as AIH. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Serum miR-29a and miR-122 as Potential Biomarkers for Non-Alcoholic Fatty Liver Disease (NAFLD).

    PubMed

    Jampoka, Kanisa; Muangpaisarn, Puth; Khongnomnan, Kritsada; Treeprasertsuk, Sombat; Tangkijvanich, Pisit; Payungporn, Sunchai

    2018-05-30

    Non-alcoholic fatty liver disease (NAFLD) is an over accumulation of triglyceride in the liver without alcohol consumption which its major cause is from insulin resistance. Patients with NAFLD can develop to be liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) are non-coding RNAs that regulate post-transcriptional gene silencing. Previous research reported that miR-29 family (a, b and c) and miR-122 have an important role in regulating insulin resistance related to NAFLD. The purpose of this study was to investigate that miR-29 and miR-122 can be possible biomarkers for non-invasive diagnosis of NAFLD. Serum samples were collected from 58 NAFLD patients and 34 healthy controls. MiRNAs were extracted from serum by using microRNA purification kit followed by polyuridylation, reverse transcription and quantitative real-time PCR. Also, we analyzed the correlation between miR-29 and miR-122 and level of liver inflammation in NAFLD patients. We found that the serum miR-29a levels in NAFLD patients were significantly lower (P = 0.006) than the control group, while miR-29c levels were unchanged, and miR-29b levels were undetectable. However, we found that serum miR-122 levels in NAFLD patients were significantly higher (P < 0.001) than those found in the control group. For miR-29a, the area under curve (AUC) was 0.679 (P = 0.0065) with 60.87% sensitivity and 82.35% specificity. For miR-122, the AUC was 0.831 (P < 0.0001) with 75.00% sensitivity and 82.35% specificity. Interestingly, the level of serum miR-122 were significantly different between patients with not steatohepatitis (NAS < 4) and steatohepatitis (NAS ≥ 4), indicating that the levels of miR-122 were related to the severity of NAFLD. The levels of miR-29a and miR-122 might be beneficial and compelling as possible biomarkers for non-invasive diagnosis of NAFLD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Correlation between non-alcoholic fatty liver disease (NAFLD) and dyslipidemia in type 2 diabetes.

    PubMed

    Krishan, Saini

    2016-01-01

    Non-alcoholic fatty liver means the presence of hepatosteatosis without significant alcohol consumption; it is strongly associated with obesity and metabolic disorder like type 2 diabetes and dyslipideamia. NASH may progress to advanced stages of hepatic fibrosis and cirrhosis. Increased body mass index and viral genotype contribute to steatosis in chronic hepatitis. The sonographic features of NAFLD include the presence of bright hepatic echotexture deep attenuation, and vascular blurring either singly or in combination. Dyslipidemia in patients with NAFLD is atherogenic in nature and it is characterized by increased levels of serum triglycerides and decreased levels of HDL cholesterol. Statins are potent lipid-lowering agents which decrease LDL cholesterol by 20-60%, decrease triglycerides by 10-33% and increase HDL cholesterol by 5-10% for the patients with NAFLD. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  10. NAFLD and Atherosclerosis Are Prevented by a Natural Dietary Supplement Containing Curcumin, Silymarin, Guggul, Chlorogenic Acid and Inulin in Mice Fed a High-Fat Diet

    PubMed Central

    Amato, Antonella; Caldara, Gaetano-Felice; Nuzzo, Domenico; Baldassano, Sara; Picone, Pasquale; Rizzo, Manfredi; Mulè, Flavia; Di Carlo, Marta

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) confers an increased risk of cardiovascular diseases. NAFDL is associated with atherogenic dyslipidemia, inflammation and renin-angiotensin system (RAS) imbalance, which in turn lead to atherosclerotic lesions. In the present study, the impact of a natural dietary supplement (NDS) containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin on NAFLD and atherosclerosis was evaluated, and the mechanism of action was examined. C57BL/6 mice were fed an HFD for 16 weeks; half of the mice were simultaneously treated with a daily oral administration (os) of the NDS. NAFLD and atherogenic lesions in aorta and carotid artery (histological analysis), hepatic expression of genes involved in the NAFLD (PCR array), hepatic angiotensinogen (AGT) and AT1R mRNA expression (real-time PCR) and plasma angiotensin (ANG)-II levels (ELISA) were evaluated. In the NDS group, steatosis, aortic lesions or carotid artery thickening was not observed. PCR array showed upregulation of some genes involved in lipid metabolism and anti-inflammatory activity (Cpt2, Ifng) and downregulation of some genes involved in pro-inflammatory response and in free fatty acid up-take (Fabp5, Socs3). Hepatic AGT, AT1R mRNA and ANG II plasma levels were significantly lower with respect to the untreated-group. Furthermore, NDS inhibited the dyslipidemia observed in the untreated animals. Altogether, these results suggest that NDS prevents NAFLD and atherogenesis by modulating the expression of different genes involved in NAFLD and avoiding RAS imbalance. PMID:28505074

  11. Transcriptional regulation of PNPLA3 and its impact on susceptibility to nonalcoholic fatty liver Disease (NAFLD) in humans

    PubMed Central

    Wang, Xiaoliang; Gawrieh, Samer; Gamazon, Eric R.; Athinarayanan, Shaminie; Liu, Yang-Lin; Darlay, Rebecca; Cordell, Heather J; Daly, Ann K

    2017-01-01

    The increased expression of PNPLA3148M leads to hepatosteatosis in mice. This study aims to investigate the genetic control of hepatic PNPLA3 transcription and to explore its impact on NAFLD risk in humans. Through a locus-wide expression quantitative trait loci (eQTL) mapping in two human liver sample sets, a PNPLA3 intronic SNP, rs139051 A>G was identified as a significant eQTL (p = 6.6×10−8) influencing PNPLA3 transcription, with the A allele significantly associated with increased PNPLA3 mRNA. An electrophoresis mobility shift assay further demonstrated that the A allele has enhanced affinity to nuclear proteins than the G allele. The impact of this eQTL on NAFLD risk was further tested in three independent populations. We found that rs139051 did not independently affect the NAFLD risk, whilst rs738409 did not significantly modulate PNPLA3 transcription but was associated with NAFLD risk. The A-G haplotype associated with higher transcription of the disease-risk rs738409 G allele conferred similar risk for NAFLD compared to the G-G haplotype that possesses a lower transcription level. Our study suggests that the pathogenic role of PNPLA3148M in NAFLD is independent of the gene transcription in humans, which may be attributed to the high endogenous transcription level of PNPLA3 gene in human livers. PMID:27744419

  12. Transcriptional regulation of PNPLA3 and its impact on susceptibility to nonalcoholic fatty liver Disease (NAFLD) in humans.

    PubMed

    Liu, Wanqing; Anstee, Quentin M; Wang, Xiaoliang; Gawrieh, Samer; Gamazon, Eric R; Athinarayanan, Shaminie; Liu, Yang-Lin; Darlay, Rebecca; Cordell, Heather J; Daly, Ann K; Day, Chris P; Chalasani, Naga

    2016-10-13

    The increased expression of PNPLA3 148M leads to hepatosteatosis in mice. This study aims to investigate the genetic control of hepatic PNPLA3 transcription and to explore its impact on NAFLD risk in humans. Through a locus-wide expression quantitative trait loci (eQTL) mapping in two human liver sample sets, a PNPLA3 intronic SNP, rs139051 A>G was identified as a significant eQTL ( p = 6.6×10 -8 ) influencing PNPLA3 transcription, with the A allele significantly associated with increased PNPLA3 mRNA. An electrophoresis mobility shift assay further demonstrated that the A allele has enhanced affinity to nuclear proteins than the G allele. The impact of this eQTL on NAFLD risk was further tested in three independent populations. We found that rs139051 did not independently affect the NAFLD risk, whilst rs738409 did not significantly modulate PNPLA3 transcription but was associated with NAFLD risk. The A-G haplotype associated with higher transcription of the disease-risk rs738409 G allele conferred similar risk for NAFLD compared to the G-G haplotype that possesses a lower transcription level. Our study suggests that the pathogenic role of PNPLA3 148M in NAFLD is independent of the gene transcription in humans, which may be attributed to the high endogenous transcription level of PNPLA3 gene in human livers.

  13. Correlation of blood glucose, serum chemerin and insulin resistance with NAFLD in patients with type 2 diabetes mellitus.

    PubMed

    Zhang, Zhengjun; Wang, Jijun; Wang, Hongmei

    2018-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a form of clinical syndrome characterized by the fatty degeneration in liver histology and should be further investigated. The aim of the study was to investigate the effects of blood glucose, serum chemerin and insulin resistance on non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus to provide a basis for the prevention and treatment thereof. In total, 300 patients with type 2 diabetes mellitus treated and admitted into the Endocrinology Department of our hospital from June 2015 to June 2017 were enrolled and divided into the simple type 2 diabetes mellitus (group A) and concurrent NAFLD (group B) groups. The sex, age, body mass index (BMI), blood pressure, blood biochemical indexes and chemerin level were compared between the two groups. The patients in group B were further divided into the mild fatty liver (group B1), moderate fatty liver (group B2) and severe fatty liver (group B3) groups. The sex, age, BMI blood pressure, blood biochemical indexes and chemerin level were also compared among the three groups. Finally, the risk factors of type 2 diabetes mellitus complicated by NAFLD were analyzed via logistic regression. The BMI, fasting plasma glucose (FPG), 2 h post-prandial plasma glucose (2hPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), alanine aminotransferase (ALT), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and HOMA-β indexes and serum chemerin level in group B were significantly higher than those in group A (P<0.05 or P<0.01). Notably, the aggravation of NAFLD, the aforementioned indexes were obviously increased (P<0.05 or P<0.01). The regression analysis revealed that BMI, FPG, TC, LDL-c, FINS, HOMA-IR and chemerin were risk factors of concurrent NAFLD. Thus, type 2 diabetes mellitus complicated by NAFLD is closely associated with severe glucose-lipid metabolism disorder and insulin

  14. Probiotics as an emerging therapeutic strategy to treat NAFLD: focus on molecular and biochemical mechanisms.

    PubMed

    Iacono, Anna; Raso, Giuseppina Mattace; Canani, Roberto Berni; Calignano, Antonio; Meli, Rosaria

    2011-08-01

    Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, both in adults and in children. NAFLD is characterized by aberrant lipid storage in hepatocytes (hepatic steatosis) and inflammatory progression to nonalcoholic steatohepatitis. Evidences so far suggest that intrahepatic lipid accumulation does not always derive from obesity. Gut microbiota has been considered as a regulator of energy homeostasis and ectopic fat deposition, suggesting its implications in metabolic diseases. Probiotics are live microbial that alter the enteric microflora and have beneficial effects on human health. Although the molecular mechanisms of probiotics have not been completely elucidated yet, many of their effects have proved to be beneficial in NAFLD, including the modulation of the intestinal microbiota, an antibacterial substance production, an improved epithelial barrier function and a reduced intestinal inflammation. Given the close anatomical and functional correlation between the bowel and the liver, and the immunoregulatory effects elicited by probiotics, the aim of this review is to summarize today's knowledge about probiotics in NAFLD, focusing in particular on their molecular and biochemical mechanisms, as well as highlighting their efficacy as an emerging therapeutic strategy to treat this condition. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice

    PubMed Central

    Chao, Jung; Huo, Teh-Ia; Cheng, Hao-Yuan; Tsai, Jen-Chieh; Liao, Jiunn-Wang; Lee, Meng-Shiou; Qin, Xue-Mei; Hsieh, Ming-Tsuen; Pao, Li-Heng; Peng, Wen-Huang

    2014-01-01

    Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help

  16. Targeted delivery of microRNA 146b mimic to hepatocytes by lactosylated PDMAEMA nanoparticles for the treatment of NAFLD.

    PubMed

    He, Shuying; Guo, Weihong; Deng, Feihong; Chen, Kequan; Jiang, Yonghong; Dong, Minyu; Peng, Liang; Chen, Xueqing

    2018-03-21

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and precision therapeutic will be a benefit for the NAFLD regression. In this study, we observed low microRNA 146 b (miR-146 b) expression in NAFLD mice model induced by methionine-choline-deficient diet (MCD) compared with control group. Furthermore, miR-146b -/- mice induced MCD exhibited severe liver steatosis and hepatitis. A bio-distribution study showed that novel Lactosylated PDMAEMA nanoparticles effectively targeted hepatocytes Lac-PDMAEMA. We coupled miR-146b mimic with Lac-PDMAEMA and then were administrated to NAFLD mice model, which could obviously alleviate the hepatic steatosis. Lac-PDMAEMA effectively delivered miR-146b mimic to hepatocytes with a ∼8-fold upregulation of miR-146b mimic targeting MyD88 and IRAK1, and in turn suppressed the expression of PPARγ. Meanwhile, TNF-α and IL-6 mRNA levels were decreased after administration of Lac-PDMAEMA/miR-146b mimic. So, we made a conclusion that targeted delivering miR-146b mimic to the hepatocytes by, coupling Lac-PDMAEMA nanoparticles could effectively alleviate the hepatic steatosis in NAFLD mice, which maybe bring a new and effective way to intervene and therapy the NAFLD.

  17. Low Dose Levothyroxine Reduces Intrahepatic Lipid Content in Patients with Type 2 Diabetes Mellitus and NAFLD.

    PubMed

    Bruinstroop, Eveline; Dalan, Rinkoo; Yang, Cao; Bee, Yong Mong; Chandran, Kurumbian; Cho, Li Wei; Soh, Shui Boon; Teo, Eng Kiong; Toh, Sue-Anne; Leow, Melvin Khee Shing; Sinha, Rohit A; Sadananthan, Suresh Anand; Michael, Navin; Stapleton, Heather; Leung, Christopher; Angus, Peter W; Patel, Sheila K; Burrell, Louise M; Chi, Lim Su; Fang, Sum Chee; Velan, S Sendhil; Yen, Paul M

    2018-04-27

    Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus and associated with significant morbidity and mortality. Thyroid hormone (TH) increases β-oxidation of fatty acids and decreases intrahepatic lipid content (IHLC) in rodents with NAFLD. In this study we investigated the possibility of low intrahepatic TH concentration in NAFLD and studied the effect of TH treatment in humans. We performed a phase 2b single arm study in six hospitals in Singapore to study whether TH reduced IHLC. Rats fed a MCD diet to induce NAFLD were used to show intrahepatic thyroid hormone concentrations. Euthyroid patients with type 2 diabetes mellitus and steatosis measured by ultrasonograpy. Levothyroxine was titrated at TSH 0.34-1.70 mIU/L before a 16-week maintenance phase. The primary outcome measure was change in IHLC measured by 1H-MRS after treatment. 20 male patients were included in the per protocol analysis (mean age 47.8±7.8 years, BMI 30.9±4.4 kg/m2, baseline IHLC 13±4 %). After treatment IHLC was decreased by 12 % ± 26 % relative to baseline (absolute change -2 %; 95% CI -3 to 0, p=0.046). Small decreases in BMI (p=0.044), VAT volume (p=0.047), and SAT volume (p=0.045) were observed. No significant changes in glucose regulation or lipid profile occurred. This is the first study demonstrating the efficacy and safety of low dose TH therapy for NAFLD in man, and suggests that TH or TH analogs may be beneficial for this condition.

  18. Potential strategies to improve uptake of exercise interventions in non-alcoholic fatty liver disease.

    PubMed

    Frith, James; Day, Christopher P; Robinson, Lisa; Elliott, Chris; Jones, David E J; Newton, Julia L

    2010-01-01

    The management of non-alcoholic liver disease (NAFLD) concerns lifestyle modification and exercise; however, adherence is poor. Factors such as lack of confidence to exercise, poor understanding of the benefits of exercise, and a fear of falling all influence engagement in physical activity. To increase exercise in NAFLD it is important to understand the barriers to performing it. Three chronic liver disease cohorts were identified from the Newcastle Liver Database: NAFLD (n=230), alcoholic liver disease (ALD, n=110) and primary biliary cirrhosis (PBC, n=97). Assessment tools were completed by all subjects: Outcome Expectation for Exercise Scale (OEES, understanding the benefits of exercise, lower scores indicate greater understanding), Self-Efficacy for Exercise Scale (SEES, confidence to exercise), Falls Efficacy Scale-International (FES-I, higher scores indicate greater fear of falling). Activity was analysed from a functional perspective using the PROMIS-HAQ. Understanding the benefits of exercise was similar across each group [median OEES scores: NAFLD 2.38 (range 0.0-5.0), ALD 2.25 (0.0-5.0), PBC 2.28 (1.0-5.0), p=0.6]. In NAFLD confidence to exercise was significantly lower [median SEES score 0.0 (0.0-10.0), PBC 4.5 (0.0-10.0), p<0.001]. Fear of falling was similar in NAFLD and PBC, and greatest in ALD [22 (0-64), 22 (3-64), 30 (0-64), p=0.044]. In NAFLD, fear of falling was independently associated with increasing difficulty performing activity. NAFLD patients understand the benefits of exercise but lack confidence to perform it. Fear of falling was independently associated with more difficulty performing activity. Fear of falling and confidence are modifiable and potential targets to improve uptake and adherence for exercise intervention.

  19. Meta-Omic Platforms to Assist in the Understanding of NAFLD Gut Microbiota Alterations: Tools and Applications

    PubMed Central

    Del Chierico, Federica; Gnani, Daniela; Vernocchi, Pamela; Petrucca, Andrea; Alisi, Anna; Dallapiccola, Bruno; Nobili, Valerio; Lorenza, Putignani

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide as a result of the increasing prevalence of obesity, starting from early life stages. It is characterized by a spectrum of liver diseases ranging from simple fatty liver (NAFL) to steatohepatitis (NASH), with a possible progression to fibrosis, thus increasing liver-related morbidity and mortality. NAFLD development is driven by the co-action of several risk factors, including obesity and metabolic syndrome, which may be both genetically induced and diet-related. Recently, particular attention has been paid to the gut-liver axis, which may play a physio-pathological role in the onset and progression of the disease. The gut microbiota is intended to act as a bioreactor that can guarantee autonomous metabolic and immunological functions and that can drive functional strategies within the environment of the body in response to external stimuli. The complexity of the gut microbiota suggests that it behaves as an organ. Therefore, the concept of the gut-liver axis must be complemented with the gut-microbiota-liver network due to the high intricacy of the microbiota components and metabolic activities; these activities form the active diet-driven power plant of the host. Such complexity can only be revealed using systems biology, which can integrate clinical phenomics and gut microbiota data. PMID:24402126

  20. Neglected features of lifestyle: Their relevance in non-alcoholic fatty liver disease

    PubMed Central

    Trovato, Francesca M; Martines, Giuseppe Fabio; Brischetto, Daniela; Trovato, Guglielmo; Catalano, Daniela

    2016-01-01

    AIM To investigated in non-alcoholic-fatty-liver-disease (NAFLD), with ultrasound (US)-detected fatty liver, and in a group of non-alcoholic and otherwise healthy subjects, relationship of neglected features of lifestyle with NAFLD and obesity. METHODS Five hundred and thirty-two NAFLD and 667 non-NAFLD healthy subjects, age 21-60 years were studied. Severity of liver steatosis was assessed by US bright liver score. The adherence to mediterranean diet score (AMDS) was assessed on the basis of a 1-wk recall computerized questionnaire which included a detailed physical activity reports (Baecke questionnaire). The western dietary profile score, as a simplified paradigm of unhealthy diet, a questionnaire quantifying sun exposure score and a sleep habits questionnaires provided a further comprehensive lifestyle assessment. RESULTS Body mass index (BMI), insulin resistance (HOMA), and triglycerides, poorer adherence to a mediterranean diet profile, sedentary habits, minor sun exposure and use of “western diet” foods are greater in NAFLD. Multiple linear regression analysis, weighted by years of age, displays BMI, HOMA and AMDS as the most powerful independent predictors of fatty liver severity; however, also the physical activity score, the western diet habit and the sun exposure score are acting inside the model with significant independent effects. CONCLUSION Articulated clinical intervention, according to our results, are justified in NAFLD and can be pursued addressing by focused intervention nutritional profile, physical exercise mainly in open-air subsets for enhancing sun exposure and healthier sleep duration and rhythm. PMID:27957244

  1. Additive Effects of the Risk Alleles of PNPLA3 and TM6SF2 on Non-alcoholic Fatty Liver Disease (NAFLD) in a Chinese Population.

    PubMed

    Wang, Xiaoliang; Liu, Zhipeng; Wang, Kai; Wang, Zhaowen; Sun, Xing; Zhong, Lin; Deng, Guilong; Song, Guohe; Sun, Baining; Peng, Zhihai; Liu, Wanqing

    2016-01-01

    Recent genome-wide association studies have identified that variants in or near PNPLA3, NCAN, GCKR, LYPLAL1, and TM6SF2 are significantly associated with non-alcoholic fatty liver disease (NAFLD) in multiple ethnic groups. Studies on their impact on NAFLD in Han Chinese are still limited. In this study, we examined the relevance of these variants to NAFLD in a community-based Han Chinese population and further explored their potential joint effect on NAFLD. Six single nucleotide polymorphisms (SNPs) (PNPLA3 rs738409, rs2294918, NCAN rs2228603, GCKR rs780094, LYPLAL1 rs12137855, and TM6SF2 rs58542926) previously identified in genome-wide analyses, to be associated with NAFLD were genotyped in 384 NAFLD patients and 384 age- and gender-matched healthy controls. We found two out of the six polymorphisms, PNPLA3 rs738409 (OR = 1.52, 95%CI: 1.19-1.96; P = 0.00087) and TM6SF2 rs58542926 (OR = 2.11, 95%CI: 1.34-3.39; P = 0.0016) are independently associated with NAFLD after adjustment for the effects of age, gender, and BMI. Our analysis further demonstrated the strong additive effects of the risk alleles of PNPLA3 and TM6SF2 with an overall significance between the number of risk alleles and NAFLD (OR = 1.64, 95%CI: 1.34-2.01; P = 1.4 × 10(-6)). The OR for NAFLD increased in an additive manner, with an average increase in OR of 1.52 per additional risk allele. Our results confirmed that the PNPLA3 and TM6SF2 variants were the most significant risk alleles for NAFLD in Chinese population. Therefore, genotyping these two genetic risk factors may help identify individuals with the highest risk of NAFLD.

  2. A vegetarian diet does not protect against nonalcoholic fatty liver disease (NAFLD): A cross-sectional study between Buddhist priests and the general population.

    PubMed

    Choi, Sung Hun; Oh, Dong Jun; Kwon, Ki Hwan; Lee, Jun Kyu; Koh, Moon Soo; Lee, Jin Ho; Kang, Hyoun Woo

    2015-07-01

    There is limited data that supports a role for a vegetarian diet in nonalcoholic fatty liver disease (NAFLD). The aim of this study is to evaluate the relationship between vegetarian diets and NAFLD, considering metabolic syndrome and obesity. This is a cross-sectional, retrospective study comparing the prevalence of NAFLD of 615 Buddhist priests and age-, sex-, Body mass index (BMI)-and presence/absence of metabolic syndrome-matched controls who underwent routine health checkups in a health promotion center. Diagnosis and severity of NAFLD was determined based on ultrasonographic findings. The prevalence of NAFLD was not statistically significantly different between the Buddhist priests and the general population (29.9% vs. 25.05%, p=0.055). The Buddhist priest group had higher serum albumin, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum triglyceride levels and lower serum total bilirubin, serum fasting glucose, and serum high density lipoprotein (HDL) levels than the general population group. In univariate analysis and multivariate analysis, NAFLD was associated with old age, male gender, increased BMI, increased waist circumference, metabolic syndrome, high albumin, high glucose, high AST, high ALT, high gamma glutamyl transpeptidase (GGT), high triglycerides, low HDL, high low density lipoprotein (LDL), and high total cholesterol. The vegetarian diet does not protect against NAFLD.

  3. Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.

    PubMed

    Pirhonen, Juho; Arola, Johanna; Sädevirta, Sanja; Luukkonen, Panu; Karppinen, Sanna-Maria; Pihlajaniemi, Taina; Isomäki, Antti; Hukkanen, Mika; Yki-Järvinen, Hannele; Ikonen, Elina

    2016-01-01

    Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD. We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0-4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals. We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III. This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading.

  4. n-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD.

    PubMed

    Vauzour, David; Rodriguez-Ramiro, Ildefonso; Rushbrook, Simon; Ipharraguerre, Ignacio R; Bevan, Damon; Davies, Susan; Tejera, Noemi; Mena, Pedro; de Pascual-Teresa, Sonia; Del Rio, Daniele; Gavrilovic, Jelena; Minihane, Anne Marie

    2018-01-01

    Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults and at present no licensed medication has been approved. Despite its complex patho-physiology, dietary strategies aiming at delaying or preventing NAFLD have taken a reductionist approach, examining the impact of single components. Accumulating evidence suggests that n-3 LC-PUFAs are efficacious in regulating lipogenesis and fatty acid oxidation. In addition, plant derived flavonoids are also emerging as a dietary strategy for NAFLD prevention, with efficacy attributed to their insulin sensitising and indirect antioxidant effects. Based on knowledge of their complementary molecular targets, we aimed to demonstrate that the combination of n-3 LC-PUFA (n-3) and flavan-3-ols (FLAV) prevents NAFLD. In a high-fat high-fructose (HF/HFr) fed C57Bl/6J mouse model, the independent and interactive impact of n-3 and FLAV on histologically defined NAFLD, insulin sensitivity, weight gain, intestinal and hepatic gene expression, intestinal bile acids were examined. Only the combination of FLAV and n-3 (FLAVn-3) prevented steatosis as evidenced by a strong reduction in hepatocyte ballooning. While FLAV reduced body (-28-30%), adipose tissue (-45-50%) weights and serum insulin (-22-25%) as observed following an intra-peritoneal glucose tolerance test, n-3 downregulated the expression of Srebf1 and the lipogenic genes (Acaca, Fasn). Significant impacts of interventions on intestinal bile acid metabolism, farnesoid X receptor (Fxr) signalling in the intestine and liver, and hepatic expression of fatty acid transporters (Fabp4, Vldlr, Cd36) were also evident. FLAVn-3 may be a novel intervention for NAFLD. Future research should aim to demonstrate its efficacy in the prevention and treatment of human NAFLD. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Hypocaloric high-protein diet improves clinical and biochemical markers in patients with nonalcoholic fatty liver disease (NAFLD).

    PubMed

    Bezerra Duarte, Sebastião Mauro; Faintuch, Joel; Stefano, José Tadeu; Sobral de Oliveira, Maria Beatriz; de Campos Mazo, Daniel Ferraz; Rabelo, Fabiola; Vanni, Denise; Nogueira, Monize Aydar; Carrilho, Flair José; Marques Souza de Oliveira, Claudia Pinto

    2014-01-01

    To investigate the role of hypocaloric highprotein diet, a prospective clinical study was conducted in NAFLD patients. Pre-versus post-interventional data were analyzed in 48 stable NAFLD patients (submitted to a hypocaloric high-protein diet during 75 days. Variables included anthropometrics (body mass index/ BMI and waist circumference/WC), whole-body and segmental bioimpedance analysis and biochemical tests. Diet compliance was assessed by interviews every two weeks. BMI, WC and body fat mass remained relatively stable (-1.3%, -1.8% and -2.5% respectively, no significance). HDL- cholesterol increased (P < 0.05) whereas total, LDL and VLDL cholesterol, triglycerides, aspartate aminotransferase/ AST, gamma glutamyltransferase/GGT, alkaline phosphatase/ AP, fasting blood glucose and glycated hemoglobin/ HbA1c decreased (P < 0.05). When patients were stratified according to increase (22/48, 45.8%) and decrease (21/48, 43.8%) of BMI, association between weight decrease and liver benefit could be elicited in such circumstances for ALT, AP and AST/ALT ratio. No change could be demonstrated in patients who gained weight. Multivariate assessment confirmed that waist circumference, ferritin, triacylglycerol, and markers of glucose homeostasis were the most relevant associated with liver enzymes. Ours results are consistent with the literature of calorie restriction in the management of NAFLD. Changes in lifestyle and weight loss are recommended for NAFLD patients. European guidelines also support this recommendation. This is the first study that demonstrated that a high protein, hypocaloric diet were associated with improvement of lipid profile, glucose homeostasis and liver enzymes in NAFLD independent on BMI decrease or body fat mass reduction.

  6. Associations between Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms and Non-Alcoholic Fatty Liver Disease (NAFLD) Risk: A Meta-Analysis

    PubMed Central

    Sun, Man-Yi; Zhang, Li; Shi, Song-Li; Lin, Jing-Na

    2016-01-01

    Background C677T and A1298C are the most common allelic variants of Methylenetetrahydrofolate Reductase (MTHFR) gene. The association between MTHFR polymorphisms and the occurrence of non-alcoholic fatty liver disease (NAFLD) remains controversial. This study was thus performed to examine whether MTHFR mutations are associated with the susceptibility to NAFLD. Methods A first meta-analysis on the association between the MTHFR polymorphisms and NAFLD risks was carried out via Review Manager 5.0 and Stata/SE 12.0 software. The on-line databases, such as PubMed, EMBASE, CENTRAL, WOS, Scopus and EBSCOhost (updated to April 1st, 2016), were searched for eligible case-control studies. The odd radio (OR), 95% confidence interval (CI) and P value were calculated through Mantel-Haenszel statistics under random- or fixed-effect model. Results Eight articles (785 cases and 1188 controls) contributed data to the current meta-analysis. For C677T, increased NAFLD risks were observed in case group under homozygote model (T/T vs C/C, OR = 1.49, 95% CI = 1.03~2.15, P = 0.04) and recessive model (T/T vs C/C+C/T, OR = 1.42, 95% CI = 1.07~1.88, P = 0.02), but not the other genetics models, compared with control group. For A1298C, significantly increased NAFLD risks were detected in allele model (C vs A, OR = 1.53, 95% CI = 1.13~2.07, P = 0.006), homozygote model (C/C vs A/A, OR = 2.81, 95% CI = 1.63~4.85, P = 0.0002), dominant model (A/C+C/C vs A/A, OR = 1.60, 95% CI = 1.06~2.41, P = 0.03) and recessive model (C/C vs A/A+A/C, OR = 2.08, 95% CI = 1.45~3.00, P<0.0001), but not heterozygote model. Conclusion T/T genotype of MTHFR C677T polymorphism and C/C genotype of MTHFR A1298C are more likely to be associated with the susceptibility to NAFLD. PMID:27128842

  7. The 'donations for decreased ALT (D4D)' prosocial behavior incentive scheme for NAFLD patients.

    PubMed

    Sumida, Yoshio; Yoshikawa, Toshikazu; Tanaka, Saiyu; Taketani, Hiroyoshi; Kanemasa, Kazuyuki; Nishimura, Tekeshi; Yamaguchi, Kanji; Mitsuyoshi, Hironori; Yasui, Kohichiroh; Minami, Masahito; Naito, Yuji; Itoh, Yoshito

    2014-12-01

    Physicians often experience difficulties in motivating patients with non-alcoholic fatty liver disease (NAFLD) to undergo lifestyle changes. The aim of this study is to examine whether 'Donations for Decreased alanine aminotransferase (ALT)' (D4D) prosocial behavior incentive can serve as an effective intrinsic motivational factor in comparison with conventional dietary and exercise intervention alone for NAFLD patients. Twenty-five NAFLD patients with elevated ALT were randomly assigned to a control group that received conventional dietary and exercise intervention alone, or a donation group whereby, as an incentive, we would make a monetary donation to the United Nations World Food Programme (WFP) based on the decrease in their ALT levels achieved over 12 weeks, in addition to receiving control intervention. In a donation group, we would donate US$1 to the WFP for every 1 IU/l of decrease in their ALT levels. There were no differences of pre-treatment clinical characteristics between the two groups. Significant reductions of ALT levels were achieved only in a donation group, although post-treatment ALT levels were not different between the two groups. These patients raised a total of $316 for the WFP. Promoting patients' intrinsic motivation by incorporating 'D4D' prosocial behavior incentive into conventional dietary and exercise intervention may provide a means to improve NAFLD. © The Author 2013. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030.

    PubMed

    Estes, Chris; Anstee, Quentin M; Arias-Loste, Maria Teresa; Bantel, Heike; Bellentani, Stefeno; Caballeria, Joan; Colombo, Massimo; Craxi, Antonio; Crespo, Javier; Day, Christopher P; Geier, Andreas; Kondili, Loreta A; Lazarus, Jeffrey V; Loomba, Rohit; Manns, Michael P; Marchesini, Giulio; Negro, Francesco; Petta, Salvatore; Ratziu, Vlad; Romero-Gomez, Manuel; Sanyal, Arun; Schattenberg, Jörn M; Tacke, Frank; Trautwein, Christian; Wei, Lai; Zeuzem, Stefan; Razavi, Homie

    2018-06-07

    Nonalcoholic fatty liver disease (NAFLD) with resulting nonalcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma (HCC) globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. A model was used to estimate NAFLD and NASH disease progression in 8 countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30%), between 2016-2030, with the highest growth in China as result of urbanization and the lowest growth in Japan as result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56%, while liver mortality and advanced liver disease will more than double as result of an aging/increasing population. NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) can lead to advanced liver disease, and are occurring in increasing numbers in tandem with epidemics of obesity and diabetes. A mathematical model was built to understand how the disease burden associated with NAFLD and NASH will change over time. Results suggest increasing numbers of cases of advanced liver disease and liver-related mortality in the coming years

  9. Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study

    PubMed Central

    Pirhonen, Juho; Arola, Johanna; Sädevirta, Sanja; Luukkonen, Panu; Karppinen, Sanna-Maria; Pihlajaniemi, Taina; Isomäki, Antti; Hukkanen, Mika

    2016-01-01

    Background and Aims Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD. Methods We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0–4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals. Results We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III. Conclusions This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading. PMID:26808140

  10. Expression of inflammation-related genes is altered in gastric tissue of patients with advanced stages of NAFLD.

    PubMed

    Mehta, Rohini; Birerdinc, Aybike; Neupane, Arpan; Shamsaddini, Amirhossein; Afendy, Arian; Elariny, Hazem; Chandhoke, Vikas; Baranova, Ancha; Younossi, Zobair M

    2013-01-01

    Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD) and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB) gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH). Expression levels of soluble interleukin 1 receptor antagonist (IL1RN) were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8), chemokine (C-C motif) ligand 4 (CCL4), and its receptor chemokine (C-C motif) receptor type 5 (CCR5) showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD.

  11. Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) in HIV.

    PubMed

    Rockstroh, Jürgen Kurt

    2017-04-01

    Abnormal liver enzymes (LE) are common in patients infected with the human immunodeficiency virus (HIV) even in the absence of viral hepatitis or alcohol abuse. With availability of antiretroviral combination therapy, life expectancy has improved dramatically and as a consequence the spectrum of liver disease is changing. Increased reports on the development of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in HIV coinfected patients raise questions around prevalence, clinical manifestations, and clinical outcome of these liver diseases in HIV coinfection. Moreover, the potential impact of combination antiretroviral therapy as well as direct HIV effects on the emergence of non-alcoholic fatty liver disease needs to be explored. This review summarizes the recent literature on NAFLD and NASH in HIV.

  12. Non-alcoholic fatty liver disease (NAFLD) and significant hepatic fibrosis defined by non-invasive assessment in patients with type 2 diabetes.

    PubMed

    Sobhonslidsuk, Abhasnee; Pulsombat, Akharawit; Kaewdoung, Piyaporn; Petraksa, Supanna

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD), the most common liver problem in diabetes, is a risk factor for liver cancer. Diabetes, high body mass index (BMI) and old age can all contribute to NAFLD progression. Transient elastography (TE) is used for non-invasive fibrosis assessment. To identify the prevalence of NAFLD and significant hepatic fibrosis in diabetic patients and to assess associated factors. One hundred and forty-one diabetic and 60 normal subjects were screened. Fatty liver was diagnosed when increased hepatic echogenicity and vascular blunting were detected by ultrasonography. Liver stiffness measurement (LSM) representing hepatic fibrosis was assessed by TE. LSM ≥7 kPa was used to define significant hepatic fibrosis. Four cases were excluded due to positive hepatitis B viral markers and failed TE. Diabetic patients had higher BMI, systolic blood pressure, waist circumference and fasting glucose levels than normal subjects. Fatty liver was diagnosed in 82 (60.7%) diabetic patients but in none of the normal group. BMI (OR: 1.31; 95%CI: 1.02-1.69; p=0.038) and alanine aminotransferase (ALT)(OR: 1.14; 95%CI: 1.05-1.23; p=0.002) were associated with NAFLD. Diabetic patients with NAFLD had higher LSM than those without [5.99 (2.4) vs 4.76 (2.7) kPa, p=0.005)]. Significant hepatic fibrosis was more common in diabetic patients than in normal subjects [22 (16.1%) vs 1 (1.7%), p=0.002]. Aspartate aminotransferase (AST)(OR: 1.24; 95%CI: 1.07-1.42; p=0.003) was associated with significant hepatic fibrosis. Sixty and sixteen percent of diabetic patients were found to have NAFLD and significant hepatic fibrosis. High BMI and ALT levels are the predictors of NAFLD, and elevated AST level is associated with significant hepatic fibrosis.

  13. Nutritional Strategies for the Individualized Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) Based on the Nutrient-Induced Insulin Output Ratio (NIOR).

    PubMed

    Stachowska, Ewa; Ryterska, Karina; Maciejewska, Dominika; Banaszczak, Marcin; Milkiewicz, Piotr; Milkiewicz, Małgorzata; Gutowska, Izabela; Ossowski, Piotr; Kaczorowska, Małgorzata; Jamioł-Milc, Dominika; Sabinicz, Anna; Napierała, Małgorzata; Wądołowska, Lidia; Raszeja-Wyszomirska, Joanna

    2016-07-22

    Nutrients play a fundamental role as regulators of the activity of enzymes involved in liver metabolism. In the general population, the action of nutrients may be affected by gene polymorphisms. Therefore, individualization of a diet for individuals with fatty liver seems to be a fundamental step in nutritional strategies. In this study, we tested the nutrient-induced insulin output ratio (NIOR), which is used to identify the correlation between the variants of genes and insulin resistance. We enrolled 171 patients, Caucasian men (n = 104) and women (n = 67), diagnosed with non-alcoholic fatty liver disease (NAFLD). From the pool of genes sensitive to nutrient content, we selected genes characterized by a strong response to the NIOR. The polymorphisms included Adrenergic receptor (b3AR), Tumor necrosis factor (TNFα), Apolipoprotein C (Apo C III). Uncoupling Protein type I (UCP-1), Peroxisome proliferator activated receptor γ2 (PPAR-2) and Apolipoprotein E (APOEs). We performed three dietary interventions: a diet consistent with the results of genotyping (NIOR (+)); typical dietary recommendations for NAFLD (Cust (+)), and a diet opposite to the genotyping results (NIOR (-) and Cust (-)). We administered the diet for six months. The most beneficial changes were observed among fat-sensitive patients who were treated with the NIOR (+) diet. These changes included improvements in body mass and insulin sensitivity and normalization of blood lipids. In people sensitive to fat, the NIOR seems to be a useful tool for determining specific strategies for the treatment of NAFLD.

  14. Obstructive sleep apnea and hypoxemia are associated with advanced liver histology in pediatric nonalcoholic fatty liver disease.

    PubMed

    Sundaram, Shikha S; Sokol, Ronald J; Capocelli, Kelley E; Pan, Zhaoxing; Sullivan, Jillian S; Robbins, Kristen; Halbower, Ann C

    2014-04-01

    To determine whether obstructive sleep apnea (OSA) and/or nocturnal hypoxemia are associated with the severity of liver injury in patients with pediatric nonalcoholic fatty liver disease (NAFLD). Obese children aged 10-18 years with liver biopsy-proven NAFLD were enrolled. Demographic, clinical, and laboratory data were collected, polysomnography was performed, and liver histology was scored. Subjects were divided into those with OSA/hypoxemia and those without OSA/hypoxemia for analysis. Of 25 subjects with NAFLD, OSA/hypoxemia was present in 15 (60%) (mean age, 12.8 ± 1.9 years; 68% male; 88% Hispanic; mean body mass index z-score, 2.3 ± 0.3). Subjects with and without OSA/hypoxemia had similar levels of serum aminotransferases, serum lipids, and inflammatory and insulin resistance markers. Although there were no differences between groups in the histological severity of steatosis, inflammation, ballooning degeneration, NAFLD activity score, or histological grade, subjects with OSA/hypoxemia had significantly more severe hepatic fibrosis. Moreover, oxygen saturation nadir during polysomnography was related to hepatic fibrosis stage (r = -0.49; P = .01) and aspartate aminotransferase level (r = 0.42; P < .05). Increasing percentage of time with oxygen saturation ≤90% was related to NAFLD inflammation grade (r = 0.44; P = .03), degree of hepatic steatosis (r = -0.50; P = .01), NAFLD activity score (r = 0.42; P = .04), aspartate aminotransferase level (r = 0.56; P = .004), and alanine aminotransferase level (r = 0.44; P = .03). Moderate OSA/hypoxemia is common in pediatric patients with biopsy-proven NAFLD. OSA and the severity/duration of hypoxemia are associated with biochemical and histological measures of NAFLD severity. Copyright © 2014 Mosby, Inc. All rights reserved.

  15. A Western diet induced NAFLD in LDLR(-/)(-) mice is associated with reduced hepatic glutathione synthesis.

    PubMed

    Li, Ling; Zhang, Guo-Fang; Lee, Kwangwon; Lopez, Rocio; Previs, Stephen F; Willard, Belinda; McCullough, Arthur; Kasumov, Takhar

    2016-07-01

    Oxidative stress plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Glutathione is the major anti-oxidant involved in cellular oxidative defense, however there are currently no simple non-invasive methods for assessing hepatic glutathione metabolism in patients with NAFLD. As a primary source of plasma glutathione, liver plays an important role in interorgan glutathione homeostasis. In this study, we have tested the hypothesis that measurements of plasma glutathione turnover could be used to assess the hepatic glutathione metabolism in LDLR(-/)(-) mice, a mouse model of diet-induced NAFLD. Mice were fed a standard low fat diet (LFD) or a high fat diet containing cholesterol (a Western type diet (WD)). The kinetics of hepatic and plasma glutathione were quantified using the (2)H2O metabolic labeling approach. Our results show that a WD leads to reduced fractional synthesis rates (FSR) of hepatic (25%/h in LFD vs. 18%/h in WD, P<0.05) and plasma glutathione (43%/h in LFD vs. 21%/h in WD, P<0.05), without any significant effect on their absolute production rates (PRs). WD-induced concordant changes in both hepatic and plasma glutathione turnover suggest that the plasma glutathione turnover measurements could be used to assess hepatic glutathione metabolism. The safety, simplicity, and low cost of the (2)H2O-based glutathione turnover approach suggest that this method has the potential for non-invasive probing of hepatic glutathione metabolism in patients with NAFLD and other diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. The ZJU index is a powerful index for identifying NAFLD in the general Chinese population.

    PubMed

    Li, Linman; You, Wenyi; Ren, Wei

    2017-10-01

    The ZJU index is a novel model for detecting non-alcoholic fatty liver disease (NAFLD) that it is calculated based on combination of the body mass index, fasting plasma glucose, triglycerides, and the serum alanine aminotransferase-to-aspartate transaminase ratio. We aimed to evaluate the diagnostic accuracy of the ZJU index in detecting NAFLD in the Chinese population. This was a cross-sectional study. Anthropometric measurements, laboratory data, and ultrasonography features were collected through a standard protocol. The ZJU index, fatty liver index, hepatic steatosis index, lipid accumulation product, and visceral adiposity index were calculated. Then the predictive values of the five indices were compared according to the area under receiver-operating characteristic curve (AUROC) values. A total of 19,804 participants were recruited, of whom 7324 participants were diagnosed with NFALD and 12,480 subjects were regarded as controls. The AUROC value for NAFLD identification by the ZJU index was 0.925 (95% confidence interval [CI]: 0.919-0.931), which was significantly higher than the values for the other four models (P < 0.001). Furthermore, from age 31 years to >60 years, the AUROC for the ZJU increased from 87.1 to 95.4%, values which were also greater than those for the other four indices. Analysis by sex also showed that the performance of the ZJU index in males and females was better than that of the other four indices. The ZJU index is an accurate and easy to employ tool for identifying NAFLD in the general Chinese population.

  17. The Effects of Ramadan Fasting on Body Composition, Blood Pressure, Glucose Metabolism, and Markers of Inflammation in NAFLD Patients: An Observational Trial.

    PubMed

    Aliasghari, Fereshteh; Izadi, Azimeh; Gargari, Bahram Pourghassem; Ebrahimi, Sara

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and is a serious global health problem. Regarding the increasing prevalence of NAFLD, finding various strategies to prevent and manage the disease is of great importance. The aim of this study was to determine the effects of caloric restriction during Ramadan fasting on anthropometric indices, fasting glucose, plasma insulin, insulin resistance, and inflammatory cytokines (C-reactive protein and interleukin 6) in patients with NAFLD. We conducted this study with 83 patients with NAFLD, 42 of whom decided to fast and 41 controls who decided not to fast for Ramadan, between June 18 and July 17, 2015. Anthropometric parameters were measured and a sample of venous blood was obtained for biochemical assays before and after Ramadan. There was a significant decrease in all anthropometric parameters as well as fasting glucose, plasma insulin, and insulin resistance. Relative to the nonfasting group, fasting significantly reduced circulating inflammatory, but changes in blood pressure after Ramadan were not significant. This study shows significant effects on parameters during Ramadan fasting such as anthropometric indices, fasting glucose, plasma insulin, and inflammatory cytokines in patients with NAFLD. The results of this study suggest that Ramadan fasting may be useful to improve NAFLD, so further studies are needed in this area.

  18. Effect of orlistat on periostin, adiponectin, inflammatory markers and ultrasound grades of fatty liver in obese NAFLD patients.

    PubMed

    Ali Khan, Rashid; Kapur, Prem; Jain, Abhinav; Farah, Farrukh; Bhandari, Uma

    2017-01-01

    Orlistat is recommended in the treatment of obesity, which is an independent risk factor for nonalcoholic fatty liver disease (NAFLD). The reported findings of orlistat in NAFLD are divisive. Recently, periostin is identified as an important regulatory molecule in the pathogenesis of obesity-induced fatty liver. Therefore, this study aimed to evaluate the potential effects of orlistat in the treatment of NAFLD. A 16-week prospective observational study was conducted, with obese NAFLD patient (n=77) receiving orlistat (120 mg capsules, three times a day) with hypocaloric diet or hypocaloric diet only. Grades of fatty liver were determined using ultrasound (US) echogenicity of liver; serum levels of periostin, adiponectin, tumor necrosis factor (TNF)-α and interleukin-6 were determined using ELISA kits at 0 and 16 weeks. Correlations of US grades of fatty liver with these biomarkers were also determined. Orlistat significantly reversed the US grades of fatty liver ( P =0.016), decreased serum levels of periostin ( P =0.030) and TNF-α ( P =0.040), and increased serum adiponectin levels ( P <0.001) when compared with hypocaloric diet only. Serum interleukin-6 levels were not found to be significantly different in both groups after the treatment. In the orlistat group, the degree of reduction in grades of fatty liver was found to be positively correlated with the changes in serum levels of periostin (r s =0.306, P =0.041) and adiponectin (r s =0.314, P =0.036), whereas the associations were insignificant with the change in serum levels of TNF-α (r s =0.053, P =0.729). Mild gastrointestinal side effects (20%) were reported in the orlistat group. In conclusion, orlistat is effective in the treatment of NAFLD patients without fibrosis. This study demonstrated a positive association between the reduction of fatty infiltration in the liver and the changes in serum levels of periostin and adiponectin in obese NAFLD patients.

  19. Effect of orlistat on periostin, adiponectin, inflammatory markers and ultrasound grades of fatty liver in obese NAFLD patients

    PubMed Central

    Ali Khan, Rashid; Kapur, Prem; Jain, Abhinav; Farah, Farrukh; Bhandari, Uma

    2017-01-01

    Orlistat is recommended in the treatment of obesity, which is an independent risk factor for nonalcoholic fatty liver disease (NAFLD). The reported findings of orlistat in NAFLD are divisive. Recently, periostin is identified as an important regulatory molecule in the pathogenesis of obesity-induced fatty liver. Therefore, this study aimed to evaluate the potential effects of orlistat in the treatment of NAFLD. A 16-week prospective observational study was conducted, with obese NAFLD patient (n=77) receiving orlistat (120 mg capsules, three times a day) with hypocaloric diet or hypocaloric diet only. Grades of fatty liver were determined using ultrasound (US) echogenicity of liver; serum levels of periostin, adiponectin, tumor necrosis factor (TNF)-α and interleukin-6 were determined using ELISA kits at 0 and 16 weeks. Correlations of US grades of fatty liver with these biomarkers were also determined. Orlistat significantly reversed the US grades of fatty liver (P=0.016), decreased serum levels of periostin (P=0.030) and TNF-α (P=0.040), and increased serum adiponectin levels (P<0.001) when compared with hypocaloric diet only. Serum interleukin-6 levels were not found to be significantly different in both groups after the treatment. In the orlistat group, the degree of reduction in grades of fatty liver was found to be positively correlated with the changes in serum levels of periostin (rs=0.306, P=0.041) and adiponectin (rs=0.314, P=0.036), whereas the associations were insignificant with the change in serum levels of TNF-α (rs=0.053, P=0.729). Mild gastrointestinal side effects (20%) were reported in the orlistat group. In conclusion, orlistat is effective in the treatment of NAFLD patients without fibrosis. This study demonstrated a positive association between the reduction of fatty infiltration in the liver and the changes in serum levels of periostin and adiponectin in obese NAFLD patients. PMID:28260907

  20. Expression of Inflammation-Related Genes Is Altered in Gastric Tissue of Patients with Advanced Stages of NAFLD

    PubMed Central

    Mehta, Rohini; Birerdinc, Aybike; Neupane, Arpan; Shamsaddini, Amirhossein; Afendy, Arian; Elariny, Hazem; Chandhoke, Vikas; Baranova, Ancha; Younossi, Zobair M.

    2013-01-01

    Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD) and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB) gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH). Expression levels of soluble interleukin 1 receptor antagonist (IL1RN) were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8), chemokine (C-C motif) ligand 4 (CCL4), and its receptor chemokine (C-C motif) receptor type 5 (CCR5) showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD. PMID:23661906

  1. Efficacy of nanocurcumin supplementation on insulin resistance, lipids, inflammatory factors and nesfatin among obese patients with non-alcoholic fatty liver disease (NAFLD): a trial protocol

    PubMed Central

    Jazayeri-Tehrani, Seyed Ali; Rezayat, Seyed Mahdi; Mansouri, Siavash; Qorbani, Mostafa; Alavian, Seyed Moayed; Daneshi-Maskooni, Milad; Hosseinzadeh-Attar, Mohammad-Javad

    2017-01-01

    Objectives Different studies have been conducted on the role of curcumin in health since having multiple properties, including antioxidant and anti-inflammatory effects. Due to the lack of studies regarding curcumin effects on obese patients with non-alcoholic fatty liver disease (NAFLD), our protocol was designed to assess nanocurcumin impacts on blood sugar, lipids, inflammatory indices, insulin resistance and liver function, especially by nesfatin. Setting This trial will be conducted in the Oil Company central hospital of Tehran, Iran with a primary level of care. Participants 84 obese patients with NAFLD diagnosed using ultrasonography will be employed according to the eligibility criteria‎. Interventions The patients will be randomly divided into two equal groups (nanocurcumin and placebo, two 40 mg capsules per day with meals for 3 months, follow-up monthly). Also, lifestyle changes (low-calorie diet and physical activity) will be advised. Measures of the primary and secondary outcomes A general questionnaire, 24 hours food recall (at the beginning, middle and end) and short-form International Physical Activity Questionnaire will be completed. Blood pressure, anthropometrics, serum sugar indices (fasting blood sugar and insulin, insulin resistance and sensitivity and glycosylated haemoglobin), lipids (triglyceride, total cholesterol and low-density and high-density lipoprotein-cholesterol, inflammatory profiles (interleukin-6, high-sensitivity C-reactive protein, and tumour necrosis factor-alpha), liver function (alanine and aspartate transaminase) and nesfatin will be measured at the beginning and end of the study. Conclusion This trial would be the first experiment to determine nanocurcumin efficacy on certain blood factors among obese patients with NAFLD. Nevertheless, studying the potential consequences of curcumin in various diseases, especially NAFLD, is required for clinical use. Trial registration number IRCT2016071915536N3; pre-results. PMID

  2. Efficacy of nanocurcumin supplementation on insulin resistance, lipids, inflammatory factors and nesfatin among obese patients with non-alcoholic fatty liver disease (NAFLD): a trial protocol.

    PubMed

    Jazayeri-Tehrani, Seyed Ali; Rezayat, Seyed Mahdi; Mansouri, Siavash; Qorbani, Mostafa; Alavian, Seyed Moayed; Daneshi-Maskooni, Milad; Hosseinzadeh-Attar, Mohammad-Javad

    2017-07-10

    Different studies have been conducted on the role of curcumin in health since having multiple properties, including antioxidant and anti-inflammatory effects. Due to the lack of studies regarding curcumin effects on obese patients with non-alcoholic fatty liver disease (NAFLD), our protocol was designed to assess nanocurcumin impacts on blood sugar, lipids, inflammatory indices, insulin resistance and liver function, especially by nesfatin. This trial will be conducted in the Oil Company central hospital of Tehran, Iran with a primary level of care. 84 obese patients with NAFLD diagnosed using ultrasonography will be employed according to the eligibility criteria‎. The patients will be randomly divided into two equal groups (nanocurcumin and placebo, two 40 mg capsules per day with meals for 3 months, follow-up monthly). Also, lifestyle changes (low-calorie diet and physical activity) will be advised. A general questionnaire, 24 hours food recall (at the beginning, middle and end) and short-form International Physical Activity Questionnaire will be completed. Blood pressure, anthropometrics, serum sugar indices (fasting blood sugar and insulin, insulin resistance and sensitivity and glycosylated haemoglobin), lipids (triglyceride, total cholesterol and low-density and high-density lipoprotein-cholesterol, inflammatory profiles (interleukin-6, high-sensitivity C-reactive protein, and tumour necrosis factor-alpha), liver function (alanine and aspartate transaminase) and nesfatin will be measured at the beginning and end of the study. This trial would be the first experiment to determine nanocurcumin efficacy on certain blood factors among obese patients with NAFLD. Nevertheless, studying the potential consequences of curcumin in various diseases, especially NAFLD, is required for clinical use. IRCT2016071915536N3; pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No

  3. Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

    PubMed

    Mendoza, Michael; Caltharp, Shelley; Song, Ming; Collin, Lindsay; Konomi, Juna V; McClain, Craig J; Vos, Miriam B

    2017-07-01

    Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P < 0.001). Copper levels were not associated with degree of fibrosis, lobular inflammation, portal inflammation, or balloon degeneration. In this cohort of pediatric subjects with NAFLD, we observed decreased tissue copper levels in subjects with NAFLD when compared with non-NAFLD subjects. In addition, tissue copper levels were lower in subjects with nonalcoholic steatohepatitis, a more severe form of the disease, when compared with steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.

  4. Liver Fat Scores Moderately Reflect Interventional Changes in Liver Fat Content by a Low-Fat Diet but Not by a Low-Carb Diet

    PubMed Central

    Kabisch, Stefan; Bäther, Sabrina; Dambeck, Ulrike; Kemper, Margrit; Gerbracht, Christiana; Honsek, Caroline; Sachno, Anna

    2018-01-01

    Background: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder all over the world, mainly being associated with a sedentary lifestyle, adiposity, and nutrient imbalance. The increasing prevalence of NAFLD accommodates similar developments for type 2 diabetes and diabetes-related comorbidities and complications. Therefore, early detection of NAFLD is an utmost necessity. Potentially helpful tools for the prediction of NAFLD are liver fat indices. The fatty liver index (FLI) and the NAFLD-liver fat score (NAFLD-LFS) have been recently introduced for this aim. However, both indices have been shown to correlate with liver fat status, but there is neither sufficient data on the longitudinal representation of liver fat change, nor proof of a diet-independent correlation between actual liver fat change and change of index values. While few data sets on low-fat diets have been published recently, low-carb diets have not been yet assessed in this context. Aim: We aim to provide such data from a highly effective short-term intervention to reduce liver fat, comparing a low-fat and a low-carb diet in subjects with prediabetes. Methods: Anthropometric measurements, magnetic resonance (MR)-based intrahepatic lipid (IHL) content, and several serum markers for liver damage have been collected in 140 subjects, completing the diet phase in this trial. Area-under-the-responder-operator-curves (AUROC) calculations as well as cross-sectional and longitudinal Spearman correlations were used. Results: Both FLI and NAFLD-LFS predict liver fat with moderate accuracy at baseline (AUROC 0.775–0.786). These results are supported by correlation analyses. Changes in liver fat, achieved by the dietary intervention, correlate moderately with changes in FLI and NAFLD-LFS in the low-fat diet, but not in the low-carb diet. A correlation analysis between change of actual IHL content and change of single elements of the liver fat indices revealed diet-specific moderate to

  5. Liver Fat Scores Moderately Reflect Interventional Changes in Liver Fat Content by a Low-Fat Diet but Not by a Low-Carb Diet.

    PubMed

    Kabisch, Stefan; Bäther, Sabrina; Dambeck, Ulrike; Kemper, Margrit; Gerbracht, Christiana; Honsek, Caroline; Sachno, Anna; Pfeiffer, Andreas F H

    2018-01-31

    Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder all over the world, mainly being associated with a sedentary lifestyle, adiposity, and nutrient imbalance. The increasing prevalence of NAFLD accommodates similar developments for type 2 diabetes and diabetes-related comorbidities and complications. Therefore, early detection of NAFLD is an utmost necessity. Potentially helpful tools for the prediction of NAFLD are liver fat indices. The fatty liver index (FLI) and the NAFLD-liver fat score (NAFLD-LFS) have been recently introduced for this aim. However, both indices have been shown to correlate with liver fat status, but there is neither sufficient data on the longitudinal representation of liver fat change, nor proof of a diet-independent correlation between actual liver fat change and change of index values. While few data sets on low-fat diets have been published recently, low-carb diets have not been yet assessed in this context. We aim to provide such data from a highly effective short-term intervention to reduce liver fat, comparing a low-fat and a low-carb diet in subjects with prediabetes. Anthropometric measurements, magnetic resonance (MR)-based intrahepatic lipid (IHL) content, and several serum markers for liver damage have been collected in 140 subjects, completing the diet phase in this trial. Area-under-the-responder-operator-curves (AUROC) calculations as well as cross-sectional and longitudinal Spearman correlations were used. Both FLI and NAFLD-LFS predict liver fat with moderate accuracy at baseline (AUROC 0.775-0.786). These results are supported by correlation analyses. Changes in liver fat, achieved by the dietary intervention, correlate moderately with changes in FLI and NAFLD-LFS in the low-fat diet, but not in the low-carb diet. A correlation analysis between change of actual IHL content and change of single elements of the liver fat indices revealed diet-specific moderate to strong correlations between ΔIHL and

  6. A Western diet induced NAFLD in LDLR−/− mice is associated with reduced hepatic glutathione synthesis

    PubMed Central

    Li, Ling; Zhang, Guo-Fang; Lee, Kwangwon; Lopez, Rocio; Previs, Stephen F.; Willard, Belinda; McCullough, Arthur; Kasumov, Takhar

    2017-01-01

    Oxidative stress plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Glutathione is the major anti-oxidant involved in cellular oxidative defense, however there are currently no simple non-invasive methods for assessing hepatic glutathione metabolism in patients with NAFLD. As a primary source of plasma glutathione, liver plays an important role in interorgan glutathione homeostasis. In this study, we have tested the hypothesis that measurements of plasma glutathione turnover could be used to assess the hepatic glutathione metabolism in LDLR−/− mice, a mouse model of diet-induced NAFLD. Mice were fed a standard low fat diet (LFD) or a high fat diet containing cholesterol (a Western type diet (WD)). The kinetics of hepatic and plasma glutathione were quantified using the 2H2O metabolic labeling approach. Our results show that a WD leads to reduced fractional synthesis rates (FSR) of hepatic (25%/h in LFD vs. 18%/h in WD, P < 0.05) and plasma glutathione (43%/h in LFD vs. 21%/h in WD, P <0.05), without any significant effect on their absolute production rates (PRs). WD-induced concordant changes in both hepatic and plasma glutathione turnover suggest that the plasma glutathione turnover measurements could be used to assess hepatic glutathione metabolism. The safety, simplicity, and low cost of the 2H2O-based glutathione turnover approach suggest that this method has the potential for non-invasive probing of hepatic glutathione metabolism in patients with NAFLD and other diseases. PMID:27036364

  7. Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis.

    PubMed

    Mohamad, Bashar; Shah, Vaishal; Onyshchenko, Mykola; Elshamy, Mohammed; Aucejo, Federico; Lopez, Rocio; Hanouneh, Ibrahim A; Alhaddad, Razan; Alkhouri, Naim

    2016-07-01

    The incidence of hepatocellular carcinoma (HCC) has increased significantly in United States over the last few decades in parallel with the epidemic of nonalcoholic fatty liver disease (NAFLD). Limited data suggests that HCC could arise in steatotic liver without the presence of cirrhosis. The present study was conducted to characterize patients with NAFLD presenting with HCC in non-cirrhotic liver (NCL) compared to the NAFLD- HCC patients in association with cirrhotic liver (CL). A retrospective analysis of all patients diagnosed with HCC and NAFLD diagnosis seen at our institution between 2003 and 2012 was done. The patients were characterized based on demographic and clinical variables as well as histological and tumor features. Comparisons between the NCL and CL groups were done using analysis of variance (ANOVA) or the non-parametric Kruskal-Wallis tests and Pearson's chi-square tests or Fisher's Exact tests as appropriate. P value of <0.05 was considered statistically significant. Thirty-six patients with NAFLD and HCC in NCL (HCC-NCL group) were identified and compared to 47 patients with NAFLD-HCC and Liver Cirrhosis (HCC-LC group). Liver fibrosis was not present in 55.9 % of patients in the HCC-NCL group (F0), stage 1 was present in 17.6 %, stage 2 in 8.8 % and stage 3 in 17.6 %. Lobular inflammation was present in 63.6 % of non-cirrhotic patients. Patients in the HCC-NCL were older (67.5 ± 12.3 vs. 62.7 ± 8.1 years), and less likely to be obese (52 % vs. 83 %) or have type 2 diabetes (38 % vs. 83 %), with p value <0.05 for all. More importantly, compared with the HCC-CL group, those in the HCC-NCL group were more likely to present with a single nodule (80.6 % vs. 52.2 %), larger nodule size (>5 cm) (77.8 % vs. 10.6 %), and receive hepatic resection as the modality of HCC treatment (66.7 % vs. 17 %); and were less likely to receive loco-regional therapy (22.3 % vs. 61.7 %) or orthotopic liver transplantation (OLT) (0 % vs. 72.3 %), with p value <0

  8. Scutellaria baicalensis regulates FFA metabolism to ameliorate NAFLD through the AMPK-mediated SREBP signaling pathway.

    PubMed

    Chen, Qian; Liu, Mengyang; Yu, Haiyang; Li, Jian; Wang, Sijian; Zhang, Yi; Qiu, Feng; Wang, Tao

    2018-06-01

    Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-A y mice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA. In KK-A y mice, S. baicalensis extract showed a decreased effect on serum and hepatic triglycerides, total cholesterols, and free fatty acid (FFA) levels after 8 weeks of treatment. In OA-induced NAFLD rats, 18 days of treatment with baicalin significantly inhibited hepatic lipid accumulation, attenuating hepatocyte hypertrophy, vacuolization and necrosis. S. baicalensis and baicalin treatment significantly suppressed the sterol regulatory element binding protein-1c (SREBP-1c) transcriptional program with downregulation of gene and protein expression of SREBP-1c (both precursor and mature fraction) and acetyl-CoA carboxylase, fatty acid synthase and stearoyl-CoA desaturase, and upregulation of AMP-activated protein kinase (AMPK), carnitine palmitoyl transferase 1 and nuclear respiratory factor 2 in the liver. Furthermore, activation of AMPK by baicalin was observed to be relative to the increase in phosphorylation of calmodulin-dependent protein kinase kinase. Taken together, S. baicalensis conferred preventive effects against FFA-induced lipotoxicity through the AMPK-mediated SREBP signaling pathway.

  9. Lower levels of insulin-like growth factor-1 standard deviation score are associated with histological severity of non-alcoholic fatty liver disease.

    PubMed

    Sumida, Yoshio; Yonei, Yoshikazu; Tanaka, Saiyu; Mori, Kojiroh; Kanemasa, Kazuyuki; Imai, Shunsuke; Taketani, Hiroyoshi; Hara, Tasuku; Seko, Yuya; Ishiba, Hiroshi; Okajima, Akira; Yamaguchi, Kanji; Moriguchi, Michihisa; Mitsuyoshi, Hironori; Yasui, Kohichiroh; Minami, Masahito; Itoh, Yoshito

    2015-07-01

    Growth hormone (GH) deficiency may be associated with histological progression of non-alcoholic fatty liver disease (NAFLD) which includes non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Insulin-like growth factor 1 (IGF-1) is mainly produced by hepatocytes and its secretion is stimulated by GH. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of IGF-1 in Japanese patients. Serum samples were obtained in 199 Japanese patients with biopsy-proven NAFLD and in 2911 sex- and age-matched healthy people undergoing health checkups. The serum levels of IGF-1 were measured using a commercially available immunoradiometric assay. The standard deviation scores (SDS) of IGF-1 according to age and sex were also calculated in NAFLD patients. The serum IGF-1 levels in NAFLD patients were significantly lower (median, 112 ng/mL) compared with the control population (median, 121 ng/mL, P < 0.0001). IGF-1 SDS less than -2.0 SD from median were found in 11.6% of 199 patients. NASH patients exhibited significantly lower levels of IGF-1 SDS (n = 130; median, -0.7) compared with NAFL patients (n = 69; median, -0.3; P = 0.026). The IGF-1 SDS values decreased significantly with increasing lobular inflammation (P < 0.001) and fibrosis (P < 0.001). In multiple regressions, the association between the IGF-1 SDS values and the severity of NAFLD persisted after adjusting for age, sex and insulin resistance. Low levels of circulating IGF-1 may have a role in the development of advanced NAFLD, independent of insulin resistance. Supplementation with GH/IGF-1 may be a candidate for the treatment of NASH. © 2014 The Japan Society of Hepatology.

  10. Systematic review with meta-analysis: the significance of histological disease severity in lean patients with nonalcoholic fatty liver disease.

    PubMed

    Sookoian, S; Pirola, C J

    2018-01-01

    Current evidence suggests that lean and obese patients with nonalcoholic fatty liver disease (NAFLD) share an altered metabolic and cardiovascular profile. However, there is an incomplete understanding of the natural history of "lean-NAFLD." Indeed, an unanswered question is whether lean (BMI ≤ 25 Kg/m 2 ) NAFLD-patients are protected from severe histological outcomes. To perform a meta-analysis with the goal of providing a quantitative estimation of the magnitude of fibrosis, as well as histological features associated with the disease severity, in lean versus overweight/obese-NAFLD patients. Through a systematic search up to July 2017, we identified eight studies that compared histological outcomes in lean (n = 493) versus overweight/obese (n = 2209) patients. Relative to lean-NAFLD, overweight/obese-NAFLD patients showed significantly (P = .032) higher fibrosis scores; the observed difference in means between the two groups, which is the absolute difference between the mean value of fibrosis score [0-4] ± standard error, was 0.28 ± 0.13. The risk of having nonalcoholic steatohepatitis-NASH (OR 0.58 95% CI 0.34-0.97) was significantly lower in lean-NAFLD (n = 322) than in overweight/obese-NAFLD (n = 1357), P = .04. Relative to lean-NAFLD, overweight/obese-NAFLD patients also have significantly greater NAFLD activity (difference in means ± SE: 0.58 ± 0.16, P = .0004) and steatosis (difference in means ± SE: 0.23 ± 0.07, P = .002) scores. Lean-NAFLD patients tend to show less severe histological features as compared to overweight/obese-NAFLD patients. Subsequent longitudinal assessment is needed to understand the clinical impact of these findings; however, the significant ~ 25% increment of mean fibrosis score in overweight/obese patients suggests that obesity could predict a worse long-term prognosis. © 2017 John Wiley & Sons Ltd.

  11. Gamma glutamyl transferase is an independent determinant for the association of insulin resistance with nonalcoholic fatty liver disease in Bangladeshi adults: Association of GGT and HOMA-IR with NAFLD.

    PubMed

    Hossain, Israt Ara; Rahman Shah, Md Mijanur; Rahman, Mohammad Khalilur; Ali, Liaquat

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with insulin resistance (HOMA-IR) syndrome. Recently serum gamma glutamyl transferase (GGT) has been considered as surrogate marker of NAFLD leading to oxidative stress and hepatocellular damage. In the present study we examined the association of serum GGT and HOMA-IR with NAFLD in Bangladeshi adult subjects. Under a cross-sectional analytical design a total of 110 subjects were recruited who came for their routine health check up in the BIHS Hospital, Darussalam, Dhaka, Bangladesh. After whole abdomen ultrasonography, 62 were diagnosed as non-NAFLD and 48 were NAFLD subjects. Serum glucose was measured by glucose-oxidase method, lipid profile and liver enzymes by enzymatic colorimetric method, glycosylated hemoglobin (HbA1c) was measured by high performance liquid chromatography (HPLC), serum insulin were measured by enzyme-linked immunosorbent assay. HOMA-IR was calculated by homeostasis model assessment (HOMA). NAFLD subjects had significantly higher levels of GGT and HOMA-IR as compared to their non-NAFLD counterparts. Multiple linear regression analysis showed a significant positive association of HOMA-IR with GGT after adjusting the effects of waist circumference (WC) and HbA1c. In binary logistic regression analysis, HOMA-IR and GGT were found to be significant determinants of NAFLD after adjusting the effects of WC and HbA1c. These results suggest that elevated levels of GGT and insulin resistance are more likely to develop NAFLD and thus support a role of these determinants in the pathogenesis of NAFLD in Bangladeshi adult subjects. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  12. Family history and obesity in youth, their effect on acylcarnitine/aminoacids metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation modeling approach

    PubMed Central

    Vadillo-Ortega, Felipe; Caballero, Augusto Enrique; Ibarra-González, Isabel; Herrera-Rosas, Arturo; Serratos-Canales, María Fabiola; León-Hernández, Mireya; González-Chávez, Antonio; Mummidi, Srinivas; Duggirala, Ravindranath

    2018-01-01

    Background Structural equation modeling (SEM) can help understanding complex functional relationships among obesity, non-alcoholic fatty liver disease (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty acids that increase oxidative stress and mitochondrial dysfunction, there would be an increase of serum acylcarnitines, amino acids and cytokines in obese subjects. Acylcarnitines would be related to non-alcoholic fatty disease that will induce insulin resistance. 2) If a positive family history of obesity and type 2 diabetes are the major determinants of the metabolomic profile, there would be higher concentration of amino acids and acylcarnitines in patients with this background that will induce obesity and NAFLD which in turn will induce insulin resistance. Methods/Results 137 normoglycemic subjects, mean age (SD) of 30.61 (8.6) years divided in three groups: BMI<25 with absence of NAFLD (G1), n = 82; BMI>30 with absence of NAFLD (G2), n = 24; and BMI>30 with NAFLD (G3), n = 31. Family history of obesity (any) was present in 53%. Both models were adjusted in SEM. Family history of obesity predicted obesity but could not predict acylcarnitines and amino acid concentrations (effect size <0.2), but did predict obesity phenotype. Conclusion Family history of obesity is the major predictor of obesity, and the metabolic abnormalities on amino acids, acylcarnitines, inflammation, insulin resistance, and NAFLD. PMID:29466466

  13. Family history and obesity in youth, their effect on acylcarnitine/aminoacids metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation modeling approach.

    PubMed

    Romero-Ibarguengoitia, Maria Elena; Vadillo-Ortega, Felipe; Caballero, Augusto Enrique; Ibarra-González, Isabel; Herrera-Rosas, Arturo; Serratos-Canales, María Fabiola; León-Hernández, Mireya; González-Chávez, Antonio; Mummidi, Srinivas; Duggirala, Ravindranath; López-Alvarenga, Juan Carlos

    2018-01-01

    Structural equation modeling (SEM) can help understanding complex functional relationships among obesity, non-alcoholic fatty liver disease (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty acids that increase oxidative stress and mitochondrial dysfunction, there would be an increase of serum acylcarnitines, amino acids and cytokines in obese subjects. Acylcarnitines would be related to non-alcoholic fatty disease that will induce insulin resistance. 2) If a positive family history of obesity and type 2 diabetes are the major determinants of the metabolomic profile, there would be higher concentration of amino acids and acylcarnitines in patients with this background that will induce obesity and NAFLD which in turn will induce insulin resistance. 137 normoglycemic subjects, mean age (SD) of 30.61 (8.6) years divided in three groups: BMI<25 with absence of NAFLD (G1), n = 82; BMI>30 with absence of NAFLD (G2), n = 24; and BMI>30 with NAFLD (G3), n = 31. Family history of obesity (any) was present in 53%. Both models were adjusted in SEM. Family history of obesity predicted obesity but could not predict acylcarnitines and amino acid concentrations (effect size <0.2), but did predict obesity phenotype. Family history of obesity is the major predictor of obesity, and the metabolic abnormalities on amino acids, acylcarnitines, inflammation, insulin resistance, and NAFLD.

  14. Betaine prevented fructose-induced NAFLD by regulating LXRα/PPARα pathway and alleviating ER stress in rats.

    PubMed

    Ge, Chen-Xu; Yu, Rong; Xu, Min-Xuan; Li, Pei-Qin; Fan, Chen-Yu; Li, Jian-Mei; Kong, Ling-Dong

    2016-01-05

    Betaine has been proven effective in treating nonalcoholic fatty liver disease (NAFLD) in animal models, however, its molecular mechanisms remain elusive. The aims of this study were to explore the mechanisms mediating the anti-inflammatory and anti-lipogenic actions of betaine in fructose-fed rats. In this study, betaine improved insulin resistance, reduced body weight gain and serum lipid levels, and prevented hepatic lipid accumulation in fructose-fed rats. It up-regulated hepatic expression of liver X receptor-alpha (LXRα) and peroxisome proliferator-activated receptor-alpha (PPARα), with the attenuation of the changes of their target genes, including hepatic carnitine palmitoyl transferase (CPT) 1α, glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1, apolipoprotein B, sterol regulatory element-binding protein 1c and adipocyte differentiation-related protein, involved in fatty acid oxidation and lipid storage in these model rats. Furthermore, betaine alleviated ER stress and inhibited acetyl-CoA carboxylase α, CPT II, stearoyl-CoA desaturase 1 and fatty acid synthase expression involved in fatty acid synthesis in the liver of fructose-fed rats. Betaine suppressed hepatic gluconeogenesis in fructose-fed rats by moderating protein kinase B -forkhead box protein O1 pathway, as well as p38 mitogen-activated protein kinase and mammalian target of rapamycin activity. Moreover, betaine inhibited hepatic nuclear factor kappa B /nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome activation-mediated inflammation in this animal model. These results demonstrated that betaine ameliorated hepatic lipid accumulation, gluconeogenesis, and inflammation through restoring LXRα and PPARα expression and alleviating ER stress in fructose-fed rats. This study provides the potential mechanisms of betaine involved in the treatment of NAFLD. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Non-alcoholic fatty liver disease (NAFLD) models in drug discovery.

    PubMed

    Cole, Banumathi K; Feaver, Ryan E; Wamhoff, Brian R; Dash, Ajit

    2018-02-01

    The progressive disease spectrum of non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), is a rapidly emerging public health crisis with no approved therapy. The diversity of various therapies under development highlights the lack of consensus around the most effective target, underscoring the need for better translatable preclinical models to study the complex progressive disease and effective therapies. Areas covered: This article reviews published literature of various mouse models of NASH used in preclinical studies, as well as complex organotypic in vitro and ex vivo liver models being developed. It discusses translational challenges associated with both kinds of models, and describes some of the studies that validate their application in NAFLD. Expert opinion: Animal models offer advantages of understanding drug distribution and effects in a whole body context, but are limited by important species differences. Human organotypic in vitro and ex vivo models with physiological relevance and translatability need to be used in a tiered manner with simpler screens. Leveraging newer technologies, like metabolomics, proteomics, and transcriptomics, and the future development of validated disease biomarkers will allow us to fully utilize the value of these models to understand disease and evaluate novel drugs in isolation or combination.

  16. A study of the prebiotic-like effects of tomato juice consumption in rats with diet-induced non-alcoholic fatty liver disease (NAFLD).

    PubMed

    García-Alonso, F J; González-Barrio, R; Martín-Pozuelo, G; Hidalgo, N; Navarro-González, I; Masuero, D; Soini, E; Vrhovsek, U; Periago, M J

    2017-10-18

    Gut microbiota may play a role in the pathogenesis of NAFLD. We investigated whether tomato juice consumption for 5 weeks could ameliorate high-fat diet-induced alterations in certain intestinal bacterial groups and products arising from their metabolism (short-chain fatty acids and microbial phenolic catabolites). For this, we used a rat model with NAFLD induced by a high-fat diet, involving four experimental groups: NA (standard diet and water), NL (standard diet and tomato juice), HA (high-fat diet and water) and HL (high-fat diet and tomato juice). The onset of NAFLD impacted the gut microbiota profile, reducing the abundance of Bifidobacterium and Lactobacillus and increasing that of Enterobacteriaceae. Also, reduced concentrations of propionate, butyrate and phenolic catabolites and an increased acetate to propionate (Ac : Pr) ratio were observed. Tomato juice intake partially ameliorated high-fat diet-induced disturbances, particularly by increasing Lactobacillus abundance and diminishing the Ac : Pr ratio, suggesting a potential improvement of the metabolic pattern of NAFLD.

  17. Toxic AGE (TAGE) Theory for the Pathophysiology of the Onset/Progression of NAFLD and ALD

    PubMed Central

    Takeuchi, Masayoshi; Takino, Jun-ichi; Sakasai-Sakai, Akiko; Takata, Takanobu; Tsutsumi, Mikihiro

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are among the most common causes of chronic liver diseases in the westernized world. NAFLD and ALD are frequently accompanied by extrahepatic complications, including hepatocellular carcinoma and cardiovascular diseases, which have a negative impact on patient survival. The chronic ingestion of an excessive daily diet containing sugar/high-fructose corn syrup increases the level of the fructose/glucose metabolite, glyceraldehyde (GA), while the chronic consumption of an excessive number of alcoholic beverages increases the level of the alcohol metabolite, acetaldehyde (AA) in the liver. GA and AA are known to react non-enzymatically with the ε- or α-amino groups of proteins, thereby generating advanced glycation end-products (AGEs, GA-AGEs, and AA-AGEs, respectively) in vivo. The interaction between GA-AGEs and the receptor for AGEs (RAGE) alters intracellular signaling, gene expression, and the release of pro-inflammatory molecules and also elicits the production of reactive oxygen species by human hepatocytes and hepatic stellate cells, all of which may contribute to the pathological changes associated with chronic liver diseases. We herein discuss the pathophysiological roles of GA-AGEs and AA-AGEs (toxic AGEs, TAGE) and a related novel theory for preventing the onset/progression of NAFLD and ALD. PMID:28632197

  18. Prediction of Nonalcoholic Fatty Liver Disease Via a Novel Panel of Serum Adipokines

    PubMed Central

    Jamali, Raika; Arj, Abbas; Razavizade, Mohsen; Aarabi, Mohammad Hossein

    2016-01-01

    Abstract Considering limitations of liver biopsy for diagnosis of nonalcoholic liver disease (NAFLD), biomarkers’ panels were proposed. The aims of this study were to establish models based on serum adipokines for discriminating NAFLD from healthy individuals and nonalcoholic steatohepatitis (NASH) from simple steatosis. This case-control study was conducted in patients with persistent elevated serum aminotransferase levels and fatty liver on ultrasound. Individuals with evidence of alcohol consumption, hepatotoxic medication, viral hepatitis, and known liver disease were excluded. Liver biopsy was performed in the remaining patients to distinguish NAFLD/NASH. Histologic findings were interpreted using “nonalcoholic fatty liver activity score.” Control group consisted of healthy volunteers with normal physical examination, liver function tests, and liver ultrasound. Binary logistic regression analysis was applied to ascertain the effects of independent variables on the likelihood that participants have NAFLD/NASH. Decreased serum adiponectin and elevated serum visfatin, IL-6, TNF-a were associated with an increased likelihood of exhibiting NAFLD. NAFLD discriminant score was developed as the following: [(−0.298 × adiponectin) + (0.022 × TNF-a) + (1.021 × Log visfatin) + (0.709 × Log IL-6) + 1.154]. In NAFLD discriminant score, 86.4% of original grouped cases were correctly classified. Discriminant score threshold value of (−0.29) yielded a sensitivity and specificity of 91% and 83% respectively, for discriminating NAFLD from healthy controls. Decreased serum adiponectin and elevated serum visfatin, IL-8, TNF-a were correlated with an increased probability of NASH. NASH discriminant score was proposed as the following: [(−0.091 × adiponectin) + (0.044 × TNF-a) + (1.017 × Log visfatin) + (0.028 × Log IL-8) − 1.787] In NASH model, 84% of original cases were correctly classified. Discriminant score threshold value of (−0.22) yielded a

  19. The Association between Pediatric NAFLD and Common Genetic Variants

    PubMed Central

    Umano, Giuseppina Rosaria; Martino, Mariangela; Santoro, Nicola

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of obesity. Several studies have shown that genetic predisposition probably plays an important role in its pathogenesis. In fact, in the last few years a large number of genetic studies have provided compelling evidence that some gene variants, especially those in genes encoding proteins regulating lipid metabolism, are associated with intra-hepatic fat accumulation. Here we provide a comprehensive review of the gene variants that have affected the natural history of the disease. PMID:28629152

  20. Minimally invasive percutaneous endovascular therapies in the management of complications of non-alcoholic fatty liver disease (NAFLD): A case report.

    PubMed

    Salsamendi, Jason; Pereira, Keith; Kang, Kyungmin; Fan, Ji

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disorders from simple steatosis to inflammation leading to fibrosis, cirrhosis, and even hepatocellular carcinoma. With the progressive epidemics of obesity and diabetes, major risk factors in the development and pathogenesis of NAFLD, the prevalence of NAFLD and its associated complications including liver failure and hepatocellular carcinoma is expected to increase by 2030 with an enormous health and economic impact. We present a patient who developed Hepatocellular carcinoma (HCC) from nonalcoholic steatohepatitis (NASH) cirrhosis. Due to morbid obesity, she was not an optimal transplant candidate and was not initially listed. After attempts for lifestyle modifications failed to lead to weight reduction, a transarterial embolization of the left gastric artery was performed. This is the sixth such procedure in humans in literature. Subsequently she had a meaningful drop in BMI from 42 to 36 over the following 6 months ultimately leading to her being listed for transplant. During this time, the left hepatic HCC was treated with chemoembolization without evidence of recurrence. In this article, we wish to highlight the use of minimally invasive percutaneous endovascular therapies such as transarterial chemoembolization (TACE) in the comprehensive management of the NAFLD spectrum and percutaneous transarterial embolization of the left gastric artery (LGA), a novel method, for the management of obesity.

  1. The characterisation of hepatic mitochondrial function in patients with non-alcoholic fatty liver disease (NAFLD) using the 13C-ketoisocaproate breath test.

    PubMed

    Afolabi, Paul R; Scorletti, Eleonora; Smith, Debbie E; Almehmadi, Amal A; Calder, Philip C; Byrne, Christopher D

    2018-06-26

    Hepatic mitochondrial function (HMF) assessed by the <sup>13</sup>C-ketoisocaproate breath test (<sup>13</sup>C-KICA BT) has been previously shown to be significantly associated with the severity of biopsy proven non-alcoholic fatty liver disease (NAFLD). However, it is uncertain whether any perturbation in HMF relates specifically to severity of liver disease or factors associated with metabolic syndrome within non-alcoholic fatty liver disease (NAFLD). Our aim was to investigate whether there was any change in HMF assessed by <sup>13</sup>C-KICA BT in patients with NAFLD compared to control subjects, and to assess the factors that are independently associated with HMF. 77 patients with NAFLD and 11 healthy control subjects were studied. HMF was assessed using <sup>13</sup>C-KICA BT and expressed as cumulative % <sup>13</sup>C-dose recovered on breath over 1hr (cPDR over 1hr). Liver fat and fibrosis was assessed by transient elastography. Multi-variable linear regression modelling was undertaken to test the independence of associations with HMF. HMF (cPDR over 1hr) was lower in NAFLD compared to controls [13.4% (4.8) v. 21.0% (6.3); p< 0.0001)]. In NAFLD, HMF was lower in patients with diabetes versus no diabetes [12.7% (3.4) v. 14.3% (6.1); p=0.003)]. Regression modelling showed age (β= -0.08; p=0.01), waist circumference (β= -0.08; p=0.01), hip circumference (β= -0.04; p=0.01), aspartate aminotransferase (AST) (β= -0.05; p=0.01) and diabetes status (β= -1.81; p=0.01) were independently associated with HMF (R<sup>2</sup>= 41.5%; p<0.0001). In patients with NAFLD (compared to healthy subjects), there was a reduction in HMF assessed by the <sup>13</sup>C-KICA BT. Furthermore, in patients with NAFLD, HMF is independent and inversely associated with age, waist and hip circumference, AST and diabetes status. © 2018 IOP Publishing Ltd.

  2. Fructose and NAFLD: The Multifaceted Aspects of  Fructose Metabolism.

    PubMed

    Jegatheesan, Prasanthi; De Bandt, Jean-Pascal

    2017-03-03

    Among various factors, such as an unhealthy diet or a sedentarity lifestyle, excessive fructose consumption is known to favor nonalcoholic fatty liver disease (NAFLD), as fructose is both a substrate and an inducer of hepatic de novo lipogenesis. The present review presents some well-established mechanisms and new clues to better understand the pathophysiology of fructose-induced NAFLD. Beyond its lipogenic effect, fructose intake is also at the onset of hepatic inflammation and cellular stress, such as oxidative and endoplasmic stress, that are key factors contributing to the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Beyond its hepatic effects, this carbohydrate may exert direct and indirect effects at the peripheral level. Excessive fructose consumption is associated, for example, with the release by the liver of several key mediators leading to alterations in the communication between the liver and the gut, muscles, and adipose tissue and to disease aggravation. These multifaceted aspects of fructose properties are in part specific to fructose, but are also shared in part with sucrose and glucose present in energy- dense beverages and foods. All these aspects must be taken into account in the development of new therapeutic strategies and thereby to better prevent NAFLD.

  3. Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression.

    PubMed

    Bellanti, Francesco; Villani, Rosanna; Tamborra, Rosanna; Blonda, Maria; Iannelli, Giuseppina; di Bello, Giorgia; Facciorusso, Antonio; Poli, Giuseppe; Iuliano, Luigi; Avolio, Carlo; Vendemiale, Gianluigi; Serviddio, Gaetano

    2018-05-01

    The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury. Copyright © 2017. Published by Elsevier B.V.

  4. Inhibition of EGFR attenuates fibrosis and stellate cell activation in diet-induced model of nonalcoholic fatty liver disease.

    PubMed

    Liang, Dandan; Chen, Hongjin; Zhao, Leping; Zhang, Wenxin; Hu, Jie; Liu, Zhiguo; Zhong, Peng; Wang, Wei; Wang, Jingying; Liang, Guang

    2018-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD begins with steatosis and advances to nonalcoholic steatohepatitis (NASH) and cirrhosis. The molecular mechanisms involved in NAFLD progression are not understood. Based on recent studies showing dysregulation of epidermal growth factor receptor (EGFR) in animal models of liver injury, we sought to determine if inhibition of EGFR mitigates liver fibrosis and HSC activation in NAFLD. We utilized the high fat diet (HFD)-induced murine model of liver injury to study the role of EGFR in NAFLD. The lipid accumulation, oxidative stress, hepatic stellate cell (HSC) activation and matrix deposition were examined in the liver tissues. We also evaluated the EGFR signaling pathway, ROS activation and pro-fibrogenic phenotype in oxidized low density lipoproteins (ox-LDL) challenged cultured HSCs. We demonstrate that EGFR was phosphorylated in liver tissues of HFD murine model of NAFLD. Inhibition of EGFR prevented diet-induced lipid accumulation, oxidative stress, and HSC activation and matrix deposition. In cultured HSCs, we show that ox-LDL caused rapid activation of the EGFR signaling pathway and induce the production of reactive oxygen species. EGFR also mediated HSC activation and promoted a pro-fibrogenic phenotype. In conclusion, our data demonstrate that EGFR plays an important role in NAFLD and is an attractive target for NAFLD therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Minimally invasive percutaneous endovascular therapies in the management of complications of non-alcoholic fatty liver disease (NAFLD): A case report

    PubMed Central

    Salsamendi, Jason; Pereira, Keith; Kang, Kyungmin; Fan, Ji

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disorders from simple steatosis to inflammation leading to fibrosis, cirrhosis, and even hepatocellular carcinoma. With the progressive epidemics of obesity and diabetes, major risk factors in the development and pathogenesis of NAFLD, the prevalence of NAFLD and its associated complications including liver failure and hepatocellular carcinoma is expected to increase by 2030 with an enormous health and economic impact. We present a patient who developed Hepatocellular carcinoma (HCC) from nonalcoholic steatohepatitis (NASH) cirrhosis. Due to morbid obesity, she was not an optimal transplant candidate and was not initially listed. After attempts for lifestyle modifications failed to lead to weight reduction, a transarterial embolization of the left gastric artery was performed. This is the sixth such procedure in humans in literature. Subsequently she had a meaningful drop in BMI from 42 to 36 over the following 6 months ultimately leading to her being listed for transplant. During this time, the left hepatic HCC was treated with chemoembolization without evidence of recurrence. In this article, we wish to highlight the use of minimally invasive percutaneous endovascular therapies such as transarterial chemoembolization (TACE) in the comprehensive management of the NAFLD spectrum and percutaneous transarterial embolization of the left gastric artery (LGA), a novel method, for the management of obesity. PMID:26629307

  6. Effects of shenling baizhu powder herbal formula on intestinal microbiota in high-fat diet-induced NAFLD rats.

    PubMed

    Zhang, Yupei; Tang, Kairui; Deng, Yuanjun; Chen, Runsen; Liang, Shu; Xie, Huijun; He, Yifang; Chen, Yanning; Yang, Qinhe

    2018-06-01

    Worldwide, non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease closely associated with obesity, diabetes and other metabolic diseases. Shenling Baizhu powder (SLBZP), a formulation of a variety of natural medicinal plants, has hepatoprotective properties and clinical efficacy in treating non-infectious intestinal disease. SLBZP has improved NAFLD symptoms; however, its mechanism of action is unknown. We established an NAFLD model in rats given a high-fat diet (HFD), administered different interventions and measured serum biochemical indices and inflammatory factors. Liver tissues were stained with hematoxylin and eosin (HE) and oil red O, and colon tissues were analyzed by immunohistochemistry. The expression profiles of liver TLR4 pathway related protein was confirmed by western blotting. Changes in intestinal microbiota composition were analyzed using a 16S rDNA sequencing technique. Of note, SLBZP effectively reduced body weight in HFD-fed rats (p < 0.05). Serum biochemical analysis indicated that SLBZP decreased the serum level of total cholesterol (TC) and improved liver function. Additionally, SLBZP decreased the serum level of endotoxin, tumor necrosis factor α (TNF-α), interleukin-1β (IL-β) (p < 0.05), and decreased the expression of TLR4 pathway related protein. Pathological examination showed that SLBZP alleviates hepatic steatosis and repairs colon mucosa. Microbiome analysis revealed that SLBZP improved the abundance of intestinal microbiota. In taxonomy-based analysis, compared with control rats, SLBZP-treated rats showed obvious changes in intestinal microbiota composition. Moreover, SLBZP increased the relative abundance of short-chain fatty acid (SCFA)-producing bacteria, including Bifidobacterium and Anaerostipes. Taken together, these results suggest that the effects of SLBZP against NAFLD may be related to the increased abundance of beneficial gut microbiota and decreased levels of LPS in the portal vein

  7. Assessment of health utilities and quality of life in patients with non-alcoholic fatty liver disease

    PubMed Central

    Sayiner, Mehmet; Stepanova, Maria; Pham, Huong; Noor, Bashir; Walters, Mercedes; Younossi, Zobair M

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease associated with increased liver-related mortality. Additionally, NAFLD could potentially impair health-related quality of life. Although an approved treatment for NAFLD does not exist, a number of new drugs for treatment of NAFLD are being developed. As the efficacy and safety of these regimens are being established, their cost-effectiveness, which requires the use of quality of life metrics and health utility scores to quality-adjusted outcomes, must also be assessed. The aim of this study was to report quality of life and health utilities in patients with NAFLD with and without cirrhosis for future use. Methods Patients with NAFLD were seen in an outpatient clinic setting. Each patient had extensive clinical data and completed the Short Form-36 (SF-36 V.1) questionnaire. The SF-6D health utility scores were calculated. Results There were 89 patients with the spectrum of NAFLD completed the SF-36 questionnaire: 59 with non-cirrhotic NAFLD and 30 with cirrhosis. Patients with NAFLD had significantly lower quality of life and health utility scores than the general population (all p<0.0001). Furthermore, patients with cirrhosis had lower quality of life and utility scores than non-cirrhotic NAFLD patients: SF-6D 0.660±0.107 in non-cirrhotic NAFLD vs 0.551±0.138 in cirrhotic NAFLD (p=0.0003). Conclusions Health utilities and quality of life scores are impaired in patients with cirrhotic NAFLD. These values should be used in cost-effectiveness analysis of the upcoming treatment regimens for advanced NAFLD. PMID:27648297

  8. A Relative Deficiency of Lysosomal Acid Lypase Activity Characterizes Non-Alcoholic Fatty Liver Disease.

    PubMed

    Tovoli, Francesco; Napoli, Lucia; Negrini, Giulia; D'Addato, Sergio; Tozzi, Giulia; D'Amico, Jessica; Piscaglia, Fabio; Bolondi, Luigi

    2017-05-25

    Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)-however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.

  9. Nonalcoholic fatty liver disease (NAFLD)--is it a new marker of hyporesponsiveness to recombinant human erythropoietin in patients that are on chronic hemodialysis?

    PubMed

    Orlic, L; Mikolasevic, I; Lukenda, V; Racki, S; Stimac, D; Milic, S

    2014-12-01

    Anemia is a major consequence of chronic kidney disease (CKD) that develops early in the course of illness and affects most patients who exhibit some degree of reduced renal function. Erythropoietin (EPO) deficiency is considered the most important cause of anemia in CKD. Renal anemia has serious clinical consequence. In addition to reducing patient physical capacity and quality of life, anemia induces adaptive cardiovascular mechanisms that increase the risk of cardiovascular disease and death. Thus, treatment of anemia in CKD is very important. While EPO is effective in correcting anemia in most cases, up to 10% of patients however, have an inadequate response to therapy. The two most common and important reasons why patients become relatively unresponsive to EPO therapy are the development of true iron deficiency and the onset of an inflammatory state that impairs the response to EPO. Indeed, the role of inflammation and pro-inflammatory cytokines in resistance to EPO therapy is gaining increasing recognition. On the other hand, the main organ for C-reactive protein (CRP) synthesis is the liver and it is well known that the synthesis of an acute-phase proteins by the liver is up regulated by inflammation. The main consequence of nonalcoholic fatty liver disease (NAFLD) is sub-chronic liver inflammation that leads and contributes to dyslipidemia, inflammation, enhanced oxidative stress and endothelial dysfunction. Considering the recent data about high prevalence of NAFLD in CKD patients, probably due to shared metabolic risk factors, we hypothesized that end-stage renal disease (ESRD) patients with NAFLD will need a much higher dose of EPO to achieve the target hemoglobin levels in comparison with ESRD patients without NAFLD. The possible underlying mechanism is sub-chronic liver inflammation in NAFLD patients that leads and contributes to poor response to EPO. Therefore, we believe that NAFLD could be a new clinical marker of poor response to EPO therapy in

  10. PNPLA3 variant and portal/periportal histological pattern in patients with biopsy-proven non-alcoholic fatty liver disease: a possible role for oxidative stress.

    PubMed

    Carpino, Guido; Pastori, Daniele; Baratta, Francesco; Overi, Diletta; Labbadia, Giancarlo; Polimeni, Licia; Di Costanzo, Alessia; Pannitteri, Gaetano; Carnevale, Roberto; Del Ben, Maria; Arca, Marcello; Violi, Francesco; Angelico, Francesco; Gaudio, Eugenio

    2017-11-17

    Pathogenesis of non-alcoholic fatty liver disease (NAFLD) is influenced by predisposing genetic variations, dysmetabolism, systemic oxidative stress, and local cellular and molecular cross-talks. Patatin-like phospholipase domain containing 3 (PNPLA3) gene I148M variant is a known determinant of NAFLD. Aims were to evaluate whether PNPLA3 I148M variant was associated with a specific histological pattern, hepatic stem/progenitor cell (HpSC) niche activation and serum oxidative stress markers. Liver biopsies were obtained from 54 NAFLD patients. The activation of HpSC compartment was evaluated by the extension of ductular reaction (DR); hepatic stellate cells, myofibroblasts (MFs), and macrophages were evaluated by immunohistochemistry. Systemic oxidative stress was assessed measuring serum levels of soluble NOX2-derived peptide (sNOX2-dp) and 8-isoprostaglandin F 2α (8-iso-PGF 2α ). PNPLA3 carriers showed higher steatosis, portal inflammation and HpSC niche activation compared to wild-type patients. DR was correlated with NAFLD activity score (NAS) and fibrosis score. Serum 8-iso-PGF 2α were significantly higher in I148M carriers compared to non-carriers and were correlated with DR and portal inflammation. sNox2-dp was correlated with NAS and with HpSC niche activation. In conclusion, NAFLD patients carrying PNPLA3 I148M are characterized by a prominent activation of HpSC niche which is associated with a more aggressive histological pattern (portal fibrogenesis) and increased oxidative stress.

  11. Efficacy of synbiotic supplementation in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of clinical trials: Synbiotic supplementation and NAFLD.

    PubMed

    Hadi, Amir; Mohammadi, Hamed; Miraghajani, Maryam; Ghaedi, Ehsan

    2018-03-27

    We systematically reviewed available randomized clinical trials (RCTs) to elucidate the overall effects of synbiotic supplementation in patients with nonalcoholic fatty liver disease (NAFLD). PubMed, Scopus, ISI Web of science and Google Scholar were searched up to December, 2017. All RCTs using synbiotic supplements to treat NAFLD included in this systematic review and meta-analysis. Mean Difference (MD) was pooled using a random-effects model. Eleven eligible databases from seven RCTs were identified for the present meta-analysis. Our results showed that synbiotic supplementation can decrease body weight, fasting blood sugar, insulin, low density lipoprotein cholesterol, total cholesterol, triglyceride, high-sensitivity C-reactive protein, tumor necrosis factor alpha, alanine transaminase and aspartate transaminase levels among patients with NAFLD. In contrast, synbiotic did not have favorable effects on body mass index (BMI), waist circumference, homeostasis model assessment for insulin resistance (HOMA-IR), and high density lipoprotein cholesterol (HDL) levels compared with the placebo group. The current study revealed that synbiotic supplementation has favorable effect on inflammatory factors, liver enzymes and some anthropometric indices, lipid profiles and glucose homeostasis parameters in patients with NAFLD.

  12. Relationship of sitting time and physical activity with non-alcoholic fatty liver disease.

    PubMed

    Ryu, Seungho; Chang, Yoosoo; Jung, Hyun-Suk; Yun, Kyung Eun; Kwon, Min-Jung; Choi, Yuni; Kim, Chan-Won; Cho, Juhee; Suh, Byung-Seong; Cho, Yong Kyun; Chung, Eun Chul; Shin, Hocheol; Kim, Yeon Soo

    2015-11-01

    The goal of this study was to examine the association of sitting time and physical activity level with non-alcoholic fatty liver disease (NAFLD) in Korean men and women and to explore whether any observed associations were mediated by adiposity. A cross-sectional study was performed on 139,056 Koreans, who underwent a health examination between March 2011 and December 2013. Physical activity level and sitting time were assessed using the validated Korean version of the international Physical Activity Questionnaire Short Form. The presence of fatty liver was determined using ultrasonographic findings. Poisson regression models with robust variance were used to evaluate the association of sitting time and physical activity level with NAFLD. Of the 139,056 subjects, 39,257 had NAFLD. In a multivariable-adjusted model, both prolonged sitting time and decreased physical activity level were independently associated with increasing prevalence of NAFLD. The prevalence ratios (95% CIs) for NAFLD comparing 5-9 and ⩾10 h/day sitting time to <5h/day were 1.04 (1.02-1.07) and 1.09 (1.06-1.11), respectively (p for trend <0.001). These associations were still observed in subjects with BMI <23 kg/m(2). The prevalence ratios (95% CIs) for NAFLD comparing minimally active and health-enhancing physically active groups to the inactive group were 0.94 (0.92-0.95) and 0.80 (0.78-0.82), respectively (p for trend <0.001). Prolonged sitting time and decreased physical activity level were positively associated with the prevalence of NAFLD in a large sample of middle-aged Koreans, supporting the importance of reducing time spent sitting in addition to promoting physical activity. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  13. New scoring system combining the FIB-4 index and cytokeratin-18 fragments for predicting steatohepatitis and liver fibrosis in patients with nonalcoholic fatty liver disease.

    PubMed

    Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Saibara, Toshiji; Ono, Masafumi; Kage, Masayoshi

    To establish a new scoring system as a noninvasive tool for predicting steatohepatitis and liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). A total of 170 patients histologically diagnosed with nonalcoholic steatohepatitis (NASH) (n = 130) or nonalcoholic fatty liver (NAFL) (n = 40) were enrolled. We analyzed receiver operating characteristic (ROC) curves and performed multivariate analysis to predict steatohepatitis and liver fibrosis. Multivariate analysis showed that cytokeratin-18 fragment (CK18-F) levels (≥278 U/L) (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.42-14.00; p = 0.010) and the FIB-4 index (≥1.46) (OR, 4.54; 95% CI, 1.93-29.50; p = 0.004) were independently associated with prediction of NASH. We then established a new scoring system (named the FIC-22 score) for predicting NASH using CK18-F levels and FIB-4 index. The areas under the ROC curve (AUROCs) of the FIC-22 score and NAFIC score were 0.82 (95% CI, 0.75-0.89) and 0.71 (95% CI, 0.62-0.78) (p = 0.044). Additionally, the AUROC of the FIC-22 score for predicting the presence of fibrosis (F ≥ 1) was 0.78 (95% CI, 0.70-0.85). In patients with NAFLD, the FIC-22 score had high predictive accuracy not only for steatohepatitis but also for the presence of liver fibrosis.

  14. Relationships between Genetic Variations of PNPLA3, TM6SF2 and Histological Features of Nonalcoholic Fatty Liver Disease in Japan.

    PubMed

    Akuta, Norio; Kawamura, Yusuke; Arase, Yasuji; Suzuki, Fumitaka; Sezaki, Hitomi; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Suzuki, Yoshiyuki; Ikeda, Kenji; Kumada, Hiromitsu

    2016-05-23

    It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.

  15. Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease

    PubMed Central

    Shoji, Hirotaka; Yoshio, Sachiyo; Mano, Yohei; Kumagai, Erina; Sugiyama, Masaya; Korenaga, Masaaki; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Aikata, Hiroshi; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Nozaki, Yuichi; Kawaguchi, Takumi; Torimura, Takuji; Abe, Masanori; Hiasa, Yoichi; Fukai, Moto; Kamiyama, Toshiya; Taketomi, Akinobu; Mizokami, Masashi; Kanto, Tatsuya

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387*IL-34 (pg/ml) + 0.3623*type IV collagen 7s (ng/ml) + 0.0184*age (year)–1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients. PMID:27363523

  16. Protein-protein interaction analysis of Alzheimer`s disease and NAFLD based on systems biology methods unhide common ancestor pathways.

    PubMed

    Karbalaei, Reza; Allahyari, Marzieh; Rezaei-Tavirani, Mostafa; Asadzadeh-Aghdaei, Hamid; Zali, Mohammad Reza

    2018-01-01

    Analysis reconstruction networks from two diseases, NAFLD and Alzheimer`s diseases and their relationship based on systems biology methods. NAFLD and Alzheimer`s diseases are two complex diseases, with progressive prevalence and high cost for countries. There are some reports on relation and same spreading pathways of these two diseases. In addition, they have some similar risk factors, exclusively lifestyle such as feeding, exercises and so on. Therefore, systems biology approach can help to discover their relationship. DisGeNET and STRING databases were sources of disease genes and constructing networks. Three plugins of Cytoscape software, including ClusterONE, ClueGO and CluePedia, were used to analyze and cluster networks and enrichment of pathways. An R package used to define best centrality method. Finally, based on degree and Betweenness, hubs and bottleneck nodes were defined. Common genes between NAFLD and Alzheimer`s disease were 190 genes that used construct a network with STRING database. The resulting network contained 182 nodes and 2591 edges and comprises from four clusters. Enrichment of these clusters separately lead to carbohydrate metabolism, long chain fatty acid and regulation of JAK-STAT and IL-17 signaling pathways, respectively. Also seven genes selected as hub-bottleneck include: IL6, AKT1, TP53, TNF, JUN, VEGFA and PPARG. Enrichment of these proteins and their first neighbors in network by OMIM database lead to diabetes and obesity as ancestors of NAFLD and AD. Systems biology methods, specifically PPI networks, can be useful for analyzing complicated related diseases. Finding Hub and bottleneck proteins should be the goal of drug designing and introducing disease markers.

  17. Zinc and Selenium Co-supplementation Reduces Some Lipid Peroxidation and Angiogenesis Markers in a Rat Model of NAFLD-Fed High Fat Diet.

    PubMed

    Mousavi, Seyedeh Neda; Faghihi, Amirhosein; Motaghinejad, Majid; Shiasi, Maryam; Imanparast, Fatemeh; Amiri, Hamid Lorvand; Shidfar, Farzad

    2018-02-01

    Studies have shown that non-alcoholic fatty liver disease (NAFLD) patients are more prone to cardiovascular disease (CVD). Zinc and selenium deficiency are common in NAFLD. But the effects of zinc and selenium co-supplementation before and/or after disease progression on CVD markers are not clear in NAFLD patients. This study aimed to compare the effects of zinc and selenium co-supplementation before and/or after disease progression on some of the CVD markers in an experimental model of NAFLD. Forty male Sprague Dawley rats (197 ± 4 g) were randomly assigned into four dietary groups: control group (C; received 9% of calorie as fat), model group (M; received 82% of calorie as fat), and supplementation before (BS) or after (AS) disease progression. Animals were fed diets for 20 weeks in all groups. Fasting plasma glucose (FPG), insulin, HOMA-IR, ALT, AST, lipid profile, malondialdehyde (MDA) and vascular endothelial growth factor (VEGF) levels were measured as CVD indices. Serum ALT, AST, FPG, insulin, MDA, VEGF and HOMA-IR were significantly higher in the M than C group. Co-supplementation reduced serum ALT and AST levels in the BS and AS groups compared with the M group. FPG, insulin, HOMA-IR, VEGF, MDA, LDL/HDL-c and TC/HDL-c ratio were significantly reduced in the AS compared with the M group. TG/HDL-c ratio was significantly reduced in the BS and AS compared with the M group. Serum MDA, VEGF, Insulin and HOMA-IR were significantly lowered in the AS than BS group (p < 0.05). Zinc and selenium co-supplementation after NAFLD progression reduced CVD risk indices in an experimental model.

  18. Dynamic Measurement of Disease Activity in Acute Pancreatitis: The Pancreatitis Activity Scoring System

    PubMed Central

    Wu, Bechien U.; Batech, Michael; Quezada, Michael; Lew, Daniel; Fujikawa, Kelly; Kung, Jonathan; Jamil, Laith H.; Chen, Wansu; Afghani, Elham; Reicher, Sonya; Buxbaum, James; Pandol, Stephen J.

    2017-01-01

    OBJECTIVES Acute pancreatitis has a highly variable course. Currently there is no widely accepted method to measure disease activity in patients hospitalized for acute pancreatitis. We aimed to develop a clinical activity index that incorporates routine clinical parameters to assist in the measurement, study, and management of acute pancreatitis. METHODS We used the UCLA/RAND appropriateness method to identify items for inclusion in the disease activity instrument. We conducted a systematic literature review followed by two sets of iterative modified Delphi meetings including a panel of international experts between November 2014 and November 2015. The final instrument was then applied to patient data obtained from five separate study cohorts across Southern California to assess profiles of disease activity. RESULTS From a list of 35 items comprising 6 domains, we identified 5 parameters for inclusion in the final weighted clinical activity scoring system: organ failure, systemic inflammatory response syndrome, abdominal pain, requirement for opiates and ability to tolerate oral intake. We applied the weighted scoring system across the 5 study cohorts comprising 3,123 patients. We identified several distinct patterns of disease activity: (i) overall there was an elevated score at baseline relative to discharge across all study cohorts, (ii) there were distinct patterns of disease activity related to duration of illness as well as (iii) early and persistent elevation of disease activity among patients with severe acute pancreatitis defined as persistent organ failure. CONCLUSIONS We present the development and initial validation of a clinical activity score for real-time assessment of disease activity in patients with acute pancreatitis. PMID:28462914

  19. Dynamic Measurement of Disease Activity in Acute Pancreatitis: The Pancreatitis Activity Scoring System.

    PubMed

    Wu, Bechien U; Batech, Michael; Quezada, Michael; Lew, Daniel; Fujikawa, Kelly; Kung, Jonathan; Jamil, Laith H; Chen, Wansu; Afghani, Elham; Reicher, Sonya; Buxbaum, James; Pandol, Stephen J

    2017-07-01

    Acute pancreatitis has a highly variable course. Currently there is no widely accepted method to measure disease activity in patients hospitalized for acute pancreatitis. We aimed to develop a clinical activity index that incorporates routine clinical parameters to assist in the measurement, study, and management of acute pancreatitis. We used the UCLA/RAND appropriateness method to identify items for inclusion in the disease activity instrument. We conducted a systematic literature review followed by two sets of iterative modified Delphi meetings including a panel of international experts between November 2014 and November 2015. The final instrument was then applied to patient data obtained from five separate study cohorts across Southern California to assess profiles of disease activity. From a list of 35 items comprising 6 domains, we identified 5 parameters for inclusion in the final weighted clinical activity scoring system: organ failure, systemic inflammatory response syndrome, abdominal pain, requirement for opiates and ability to tolerate oral intake. We applied the weighted scoring system across the 5 study cohorts comprising 3,123 patients. We identified several distinct patterns of disease activity: (i) overall there was an elevated score at baseline relative to discharge across all study cohorts, (ii) there were distinct patterns of disease activity related to duration of illness as well as (iii) early and persistent elevation of disease activity among patients with severe acute pancreatitis defined as persistent organ failure. We present the development and initial validation of a clinical activity score for real-time assessment of disease activity in patients with acute pancreatitis.

  20. Challenges and Management of Liver Cirrhosis: Practical Issues in the Therapy of Patients with Cirrhosis due to NAFLD and NASH.

    PubMed

    Traussnigg, Stefan; Kienbacher, Christian; Halilbasic, Emina; Rechling, Christian; Kazemi-Shirazi, Lili; Hofer, Harald; Munda, Petra; Trauner, Michael

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. The therapeutic options in NAFLD/NASH include lifestyle modification, pharmacological treatment, bariatric surgery for patients with morbid obesity and treatment of complications of liver cirrhosis and HCC, including liver transplantation. Insulin sensitizers and antioxidative treatment strategies with vitamin E are among the best-established pharmacological approaches, but both drugs have long-term safety issues and there is limited evidence in cirrhotic patients. Treatment of concomitant/underlying metabolic conditions with statins or metformin may also have beneficial effects on portal hypertension, complications of liver cirrhosis and HCC prevention. The bile acid receptor FXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies. Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH. © 2015 S. Karger AG, Basel.

  1. A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population.

    PubMed

    Verrijken, A; Beckers, S; Francque, S; Hilden, H; Caron, S; Zegers, D; Ruppert, M; Hubens, G; Van Marck, E; Michielsen, P; Staels, B; Taskinen, M-R; Van Hul, W; Van Gaal, L

    2013-10-01

    Mechanisms explaining the relationship in non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance are poorly understood. A genetic basis has been suggested. We studied the association between the genes patatin-like phospholipase domain-containing protein 3 (PNPLA3) and apolipoprotein C3 (APOC3) and metabolic and histological parameters of NAFLD in obese patients. Overweight and obese patients underwent a metabolic and liver assessment. If NAFLD was suspected, liver biopsy was proposed. APOC3 variant rs2854117 and PNPLA3 variant rs738409 were genotyped. Four hundred seventy patients were included (61.1% had liver biopsy). The percentage of patients with non-alcoholic steatohepatitis (NASH) was significantly different according to the PNPLA3 variant. After adjustment for age and body mass index, the PNPLA3 variant was associated with alanine aminotransferase (P < 0.001) and aspartate aminotransferase (P < 0.001). The PNPLA3 variant was associated with more severe features of steatohepatitis: steatosis (P < 0.001), lobular inflammation (P < 0.001), and ballooning (P = 0.002), but not with liver fibrosis, anthropometry, or insulin resistance. No significant difference in liver histology, anthropometric, or metabolic parameters was found between carriers and non-carriers of the APOC3 variant. PNPLA3 polymorphism rs738409 was associated with NASH and the severity of necroinflammatory changes independently of metabolic factors. No association between APOC3 gene variant rs2854117 and histological or metabolic parameters of NAFLD was found. Copyright © 2013 The Obesity Society.

  2. Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity of the non-alcoholic fatty liver disease.

    PubMed

    Gelli, Chiara; Tarocchi, Mirko; Abenavoli, Ludovico; Di Renzo, Laura; Galli, Andrea; De Lorenzo, Antonino

    2017-05-07

    To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease (NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes. Forty-six adults with NAFLD received a 6-mo clinical and a dietary intervention (based on Mediterranean diet) carried out respectively by a gastroenterologist and a nutritionist with counseling license. The counseling process consisted of monthly meeting (about 45 min each). The effect of the treatment was evaluated monitoring liver enzymes, metabolic parameters, cardiovascular risk indexes, NAFLD severity [assessed by ultrasound (US)] and related indexes. All parameters were assessed at baseline. Biochemistry was also assessed at mid- and end-interventions and US was repeated at end-intervention. The percentage of patients with steatosis grade equal or higher than 2 was reduced from 93% to 48% and steatosis regressed in 9 patients (20%). At the end of the treatment the end-point concerning the weight ( i.e ., a 7% weight reduction or achievement/maintenance of normal weight) was accomplished by 25 out of 46 patients ( i.e ., 54.3%). As far as the liver enzymes is concerned, all three liver enzymes significantly decrease during the treatment the normalization was particularly evident for the ALT enzyme (altered values reduced from 67% down to 11%). Several parameters, i.e ., BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, HDL, serum glucose, Tot-Chol/HDL, LDL/HDL, TG/HDL, AIP, HOMA, FLI, Kotronen index, VAI, NAFLD liver fat score and LAP, showed a significant improvement ( P < 0.01) between baseline and end-treatment. Outcomes of this study further strengthen the hypothesis that MedDiet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states. The proposed approach may be proposed as a valid and recommended approach for improving the clinical profile of NAFLD patients.

  3. LPSF/GQ-02 inhibits the development of hepatic steatosis and inflammation in a mouse model of non-alcoholic fatty liver disease (NAFLD).

    PubMed

    Soares e Silva, Amanda Karolina; de Oliveira Cipriano Torres, Dilênia; dos Santos Gomes, Fabiana Oliveira; dos Santos Silva, Bruna; Lima Ribeiro, Edlene; Costa Oliveira, Amanda; dos Santos, Laise Aline Martins; de Lima, Maria do Carmo Alves; Pitta, Ivan da Rocha; Peixoto, Christina Alves

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) defines a wide spectrum of liver diseases that extends from simple steatosis to non-alcoholic steatohepatitis. Although the pathogenesis of NAFLD remains undefined, it is recognized that insulin resistance is present in almost all patients who develop this disease. Thiazolidinediones (TZDs) act as an insulin sensitizer and have been used in the treatment of patients with type 2 diabetes and other insulin-resistant conditions, including NAFLD. Hence, therapy of NAFLD with insulin-sensitizing drugs should ideally improve the key hepatic histological changes, while also reducing cardiometabolic and cancer risks. Controversially, TZDs are associated with the development of cardiovascular events and liver problems. Therefore, there is a need for the development of new therapeutic strategies to improve liver function in patients with chronic liver diseases. The aim of the present study was to assess the therapeutic effects of LPSF/GQ-02 on the liver of LDLR-/- mice after a high-fat diet. Eighty male mice were divided into 4 groups and two different experiments: 1-received a standard diet; 2-fed with a high-fat diet (HFD); 3-HFD+pioglitazone; 4-HFD+LPSF/GQ-02. The experiments were conducted for 10 or 12 weeks and in the last two or four weeks respectively, the drugs were administered daily by gavage. The results obtained with an NAFLD murine model indicated that LPSF/GQ-02 was effective in improving the hepatic architecture, decreasing fat accumulation, reducing the amount of collagen, decreasing inflammation by reducing IL-6, iNOS, COX-2 and F4 / 80, and increasing the protein expression of IκBα, cytoplasmic NFκB-65, eNOS and IRS-1 in mice LDLR -/-. These results suggest a direct action by LPSF/GQ-02 on the factors that affect inflammation, insulin resistance and fat accumulation in the liver of these animals. Further studies are being conducted in our laboratory to investigate the possible mechanism of action of LPSF/GQ-02 on

  4. Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation.

    PubMed

    Porras, David; Nistal, Esther; Martínez-Flórez, Susana; Pisonero-Vaquero, Sandra; Olcoz, José Luis; Jover, Ramiro; González-Gallego, Javier; García-Mediavilla, María Victoria; Sánchez-Campos, Sonia

    2017-01-01

    Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks. HFD induced obesity, metabolic syndrome and the development of hepatic steatosis as main hepatic histological finding. Increased accumulation of intrahepatic lipids was associated with altered gene expression related to lipid metabolism, as a result of deregulation of their major modulators. Quercetin supplementation decreased insulin resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1 (CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota composition was determined via 16S ribosomal RNA Illumina next-generation sequencing. Metagenomic studies revealed HFD-dependent differences at phylum, class and genus levels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetes ratio and in Gram-negative bacteria, and a dramatically increased detection of Helicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrier dysfunction and gut-liver axis alteration and subsequent inflammatory gene overexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-κB signaling pathway activation was associated with inflammasome initiation response and reticulum stress pathway induction. Quercetin reverted gut microbiota imbalance and related endotoxemia

  5. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice

    PubMed Central

    Dulai, Parambir S.; Sirlin, Claude B.; Loomba, Rohit

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease, and its prevalence is rising worldwide. The occurrence of nonalcoholic steatohepatitis (NASH) is associated with a substantial increase in disease related morbidity and mortality. Accordingly, there has been a surge of innovation surrounding drug development in an effort to off-set the natural progression and long-term risks of this disease. Disease assessment within clinical trials and clinical practice for NAFLD is currently done with liver biopsies. Liver biopsy-based assessments, however, remain imprecise and are not without cost or risk. This carries significant implications for the feasibility and costs of bringing therapeutic interventions to market. A need therefore arises for reliable and highly accurate surrogate end-points that can be used in phase 2 and 3 clinical trials to reduce trial size requirements and costs, while improving feasibility and ease of implementation in clinical practice. Significant advances have now been made in magnetic resonance technology, and magnetic resonance imaging (MRI) and elastrography (MRE) have been demonstrated to be highly accurate diagnostic tools for the detection of hepatic steatosis and fibrosis. In this review article, we will summarize the currently available evidence regarding the use of MRI and MRE among NAFLD patients, and the evolving role these surrogate biomarkers will play in the rapidly advancing arena of clinical trials in NASH and hepatic fibrosis. Furthermore, we will highlight how these tools can be readily applied to routine clinical practice, where the growing burden of NAFLD will need to be met with enhanced monitoring algorithms. PMID:27312947

  6. A retinoic acid receptor β2 agonist reduces hepatic stellate cell activation in nonalcoholic fatty liver disease.

    PubMed

    Trasino, Steven E; Tang, Xiao-Han; Jessurun, Jose; Gudas, Lorraine J

    2016-10-01

    Hepatic stellate cells (HSCs) are an important cellular target for the development of novel pharmacological therapies to prevent and treat nonalcoholic fatty liver diseases (NAFLD). Using a high fat diet (HFD) model of NAFLD, we sought to determine if synthetic selective agonists for retinoic acid receptor β2 (RARβ2) and RARγ can mitigate HSC activation and HSC relevant signaling pathways during early stages of NAFLD, before the onset of liver injury. We demonstrate that the highly selective RARβ2 agonist, AC261066, can reduce the activation of HSCs, marked by decreased HSC expression of α-smooth muscle actin (α-SMA), in mice with HFD-induced NAFLD. Livers of HFD-fed mice treated with AC261066 exhibited reduced steatosis, oxidative stress, and expression of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNFα), interleukin 1β (IL-1β), and monocyte chemotactic protein-1 (MCP-1). Kupffer cell (macrophage) expression of transforming growth factor-β1 (TGF-β1), which plays a critical role in early HSC activation, was markedly reduced in AC261066-treated, HFD-fed mice. In contrast, HFD-fed mice treated with an RARγ agonist (CD1530) showed no decreases in steatosis, HSC activation, or Kupffer cell TGF-β1 levels. In conclusion, our data demonstrate that RARβ2 is an attractive target for development of NAFLD therapies. • Hepatic stellate cells (HSCs) are an important pharmacological target for the prevention of nonalcoholic fatty liver diseases (NAFLD). • Retinoids and retinoic acid receptors (RARs) possess favorable metabolic modulating properties. • We show that an agonist for retinoic acid receptor-β2 (RARβ2), but not RARγ, mitigates HSC activation and NAFLD.

  7. Reduction of Caloric Intake Might Override the Prosteatotic Effects of the PNPLA3 p.I148M and TM6SF2 p.E167K Variants in Patients with Fatty Liver: Ultrasound-Based Prospective Study.

    PubMed

    Krawczyk, Marcin; Stachowska, Ewa; Milkiewicz, Piotr; Lammert, Frank; Milkiewicz, Malgorzata

    2016-01-01

    The adiponutrin (PNPLA3) p.I148M and transmembrane 6 superfamily member 2 (TM6SF2) p.E167K variants represent risk factors for non-alcoholic fatty liver disease (NAFLD). In this study, we assessed the effects of caloric restriction on liver phenotypes in NAFLD patients in relation to the PNPLA3 and TM6SF2 genotypes. We genotyped both variants in 143 individuals with NAFLD (55 females, age 18-74 years) and 180 controls (85 females, age 33-66 years). Liver steatosis was assessed using the ultrasound-based Hamaguchi score. A 4-month dietetic intervention, consisting of restriction of daily caloric intake without changes in physical activity, was performed. Both PNPLA3 (p = 0.002) and TM6SF2 (p = 0.041) variants were associated with NAFLD before intervention. Overall, 88 patients completed the intervention, which led to a significant decrease of steatosis, ALT activities, body mass index, hip and waist circumferences, and waist-hip ratio (all p < 0.0001). Hepatic steatosis and anthropometric traits improved significantly (p < 0.05) in carriers of either PNPLA3 or TM6SF2 risk genotype. The improvement of phenotypic traits, apart from WHR (p = 0.02), was not modified by the presence of PNPLA3 or TM6SF2 variants. The PNPLA3 and TM6SF2 polymorphisms are associated with NAFLD assessed by the Hamaguchi score. Neither PNPLA3 nor TM6SF2 risk alleles impair the response to dietetic intervention in NAFLD. © 2016 S. Karger AG, Basel.

  8. The effect of a low fructose and low glycemic index/load (FRAGILE) dietary intervention on indices of liver function, cardiometabolic risk factors, and body composition in children and adolescents with nonalcoholic fatty liver disease (NAFLD).

    PubMed

    Mager, Diana R; Iñiguez, Ingrid Rivera; Gilmour, Susan; Yap, Jason

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a common liver disease in obese children. Diets high in added fructose (high fructose corn syrup; HFCS) and glycemic index (GI)/glycemic load (GL) are associated with increased risk of NAFLD. Lifestyle modification is the main treatment, but no guidelines regarding specific dietary interventions for childhood NAFLD exist. We hypothesized that reductions in dietary fructose (total, free, and HFCS)/GI/GL over 6 months would result in improvements in body composition and markers of liver dysfunction and cardiometabolic risk in childhood NAFLD. Children and adolescents with NAFLD (n = 12) and healthy controls (n = 14) 7-18 years were studied at baseline and 3 and 6 months post-dietary intervention. Plasma markers of liver dysfunction (ALT, AST, γGT), cardiometabolic risk (TG, total cholesterol, LDL-HDL cholesterol, Apo-B100, Apo-B48, Apo-CIII, insulin, homeostasis model of assessment of insulin resistance [HOMA-IR]), inflammation (TNF-α, IL-6, IL-10), anthropometric, and blood pressure (BP) were studied using validated methodologies. Significant reductions in systolic BP (SBP), percentage body fat (BF), and plasma concentrations of ALT (P = .04), Apo-B100 (P < .001), and HOMA-IR were observed in children with NAFLD at 3 and 6 months (P < .05). Dietary reductions in total/free fructose/HFCS and GL were related to reductions in SBP (P = .01), ALT (P = .004), HOMA-IR (P = .03), and percentage BF in children with NAFLD. Reductions in dietary GI were associated with reduced plasma Apo-B100 (P = .02) in both groups. With the exception of Apo-B100, no changes in laboratory variables were observed in the control group. Modest reductions in fructose (total/free, HFCS) and GI/GL intake result in improvements of plasma markers of liver dysfunction and cardiometabolic risk in childhood NAFLD. © 2013 American Society for Parenteral and Enteral Nutrition.

  9. The hepatoprotective effect of Phyllanthus emblica L. fruit on high fat diet-induced non-alcoholic fatty liver disease (NAFLD) in SD rats.

    PubMed

    Huang, Cheng-Ze; Tung, Yu-Tang; Hsia, Shih-Min; Wu, Chi-Hao; Yen, Gow-Chin

    2017-02-22

    Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is closely associated with metabolic syndrome and refers to the accumulation of hepatic steatosis not due to excess alcohol consumption. Phyllanthus emblica L. is a rich source of gallic acid and many known medicinally phytochemicals such as tannins, lignans, flavonoids, alkaloids, vitamin C, mucic acid, and ellagic acid. Our previous study has revealed that P. emblica exhibits inhibitory effects on hepatic steatosis and liver fibrosis in vitro, as well as gallic acid improves high fat diet (HFD)-induced dyslipidaemia, hepatosteatosis, and oxidative stress in vivo. Therefore, the aim of this study was to investigate the hepatoprotective effect of the water extract of P. emblica L. fruit (WEPE) on NAFLD in an animal model. The results showed that WEPE could significantly decrease body weight, peritoneal fat and epididymal fat, enhance the antioxidant enzyme activities, and improve steatosis through elevating adiponectin in adipocytes and PPAR-α in the liver as well as lowering SREBP-1c in the liver of rats fed with a high fat diet (HFD). This might be an explanation for the hepatic fat deposition-lowering effect of WEPE. These results demonstrate that WEPE could be beneficial for the amelioration of HFD-induced steatosis.

  10. Nursing Activities Score: Cloud Computerized Structure.

    PubMed

    Moraes, Kátia Bottega; Martins, Fabiana Zerbieri; de Camargo, Maximiliano Dutra; Vieira, Débora Feijó; Magalhães, Ana Maria Muller; Silveira, Denise Tolfo

    2016-01-01

    This study objective to describe the cloud Nursing Activities Score implementation process in the Intensive Care Unit of the Post-Anesthesia Recovery Room. It is a case study. The tools used were the Google applications with high productivity interconnecting the topic knowledge on behalf of the nursing professionals and information technology professionals. As partial results, it was determined that the average nursing staff workload in the ICU/PARR during the first 24 hours, according to the score on the scale, was 91.75 ± 18.2. Each point of NAS is converted into 14.4 minutes, which is equivalent to an average of 22 working hours. Currently the instrument is implemented in the institution, reinforcing the need to update and raise awareness concerning the need to maintain the new routine.

  11. Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD).

    PubMed

    Pérez-Martínez, Laura; Pérez-Matute, Patricia; Aguilera-Lizarraga, Javier; Rubio-Mediavilla, Susana; Narro, Judit; Recio, Emma; Ochoa-Callejero, Laura; Oteo, José-Antonio; Blanco, José-Ramón

    2014-07-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. The NAFLD spectrum ranges from simple steatosis to cirrhosis. The chemokine CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis. The objective of this study was to examine the effects of maraviroc, a CCR5 antagonist, on liver pathology in a NAFLD mouse model. A total of 32 male C57BL/6 mice were randomly assigned to one of four groups: (i) control group (chow diet plus tap water); (ii) maraviroc group (chow diet plus maraviroc in drinking water); (iii) high-fat diet (HFD) group (HFD plus tap water); and (iv) maraviroc/HFD group (HFD plus maraviroc). All mice were sacrificed 16 weeks after the beginning of the experiment. Biochemical analyses and liver examinations were performed. Mice in the HFD group showed a tendency towards increased body mass gain and liver damage compared with the maraviroc/HFD group. Moreover, liver weight in the HFD group was significantly higher than in the maraviroc/HFD group. Hepatic triglyceride concentration in the maraviroc/HFD group was significantly lower than in the HFD group. Interestingly, the maraviroc/HFD group exhibited a lower degree of steatosis. Furthermore, hepatic CCL5/RANTES expression was significantly lower in the maraviroc/HFD group than in the HFD group. Overall, no differences were observed between the control group and the maraviroc group. Maraviroc ameliorates hepatic steatosis in an experimental model of NAFLD. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Non-alcoholic fatty liver disease (NAFLD) in different populations: A clinical and epidemiological study - sample of São José do Rio Preto.

    PubMed

    Andrade, Gabriel Costa de; Fujise, Luciana Harumi; Santana, Jaime Euclides de; Oliveira, Fabiane; Silva, Rita de Cássia Martins Alves da

    2016-01-01

    NAFLD is an heterogeneous condition that includes steatosis and non-alcoholic steatohepatitis (NASH), in the absence of significant alcohol consumption, reaching 30% of the population. The most common risk factors are: age, gender, ethnicity, diabetes mellitus (DM), obesity, predisposition, metabolic syndrome (MS), insulin resistance (IR), drugs, and polycystic ovary syndrome. To describe the profile of patients with NAFLD seen at Hospital de Base of Rio Preto, in the state of São Paulo. Patients with NAFLD were assessed, with medical and epidemiological data collected after informed consent. Of the 62 patients evaluated, 76% were women, 73% Caucasians, and 71% were aged between 50 and 69 years and had no symptoms. Ultrasonography results showed steatosis in 84%. NASH was diagnosed in 61% of the sample. 21 patients underwent liver biopsy, of which 36% had cirrhosis, 1 had liver cancer, and 1 pure steatosis (5% each). Risk factors were found in 70% of patients with metabolic syndrome, 87% with increased waist circumference, 63% with dyslipidemia, 61% (n=38) with high blood pressure (HBP), 28% with DM, 52% physically inactive, and 44% with insulin resistance (IR) (HOMA> 3.5). There was an association between IR and NASH (p=0.013), IR and obesity (p=0.027), IR and MS (p=0.006), and MS and steatosis on medical ultrasound (USG) (p=0.014). The most frequent risk factors were MS and its variables: increased waist circumference, dyslipidemia and HBP. This underscores the importance of metabolic control in NAFLD and confirms its role as the hepatic component of metabolic syndrome.

  13. Abnormality of autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease.

    PubMed

    Fukuo, Yuka; Yamashina, Shunhei; Sonoue, Hiroshi; Arakawa, Atsushi; Nakadera, Eisuke; Aoyama, Tomonori; Uchiyama, Akira; Kon, Kazuyoshi; Ikejima, Kenichi; Watanabe, Sumio

    2014-09-01

    Recent evidences indicate that hepatic steatosis suppresses autophagic proteolysis. The present study evaluated the correlation between autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease (NAFLD). Liver biopsy specimens were obtained from patients with chronic liver diseases (chronic hepatitis C [CHC; n = 20], chronic hepatitis B [CHB; n = 16], primary biliary cirrhosis [PBC; n = 23], NAFLD [n = 22] and control [n = 14]). The number of autophagic vesicles in hepatocytes was counted by using transmission electron microscopy. Expression of cathepsin B, D, L and p62 in the liver section was analyzed by immunohistochemical staining. The histological severity of NAFLD is assessed by NAFLD activity score (NAS). The number of autophagic vesicles in hepatocytes was significantly increased in both CHC and NAFLD groups, but not CHB and PBC, more than control. Although hepatocytes with aggregation of p62 were observed in less than 15% of CHC, p62 aggregation was detected in approximately 65% of NAFLD. Cathepsin B, D and L expression was significantly suppressed in the liver from NAFLD patients. Suppression of cathepsin B, D and L expression was not observed in CHB, CHC and PBC. In NAFLD patients, p62 aggregation was correlated with serum alanine aminotransferase value and inflammatory activity by NAS. These results indicate that a decrease in hepatic cathepsin expression in NAFLD is associated with autophagic dysfunction. Hepatic inflammation correlates with autophagic dysfunction in NAFLD. These findings indicate that the suppression of autophagic proteolysis by hepatic steatosis is involved in the pathogenesis of NAFLD. © 2013 The Japan Society of Hepatology.

  14. A Computational Model of Hepatic Energy Metabolism: Understanding Zonated Damage and Steatosis in NAFLD

    PubMed Central

    Ashworth, William B.; Bogle, I. David L.

    2016-01-01

    build-up of glucose intermediates was less severe in the periportal hepatocyte compartments. Secondly, the periportal zonation of the enzymes mediating β-oxidation and oxidative phosphorylation resulted in excess fats being metabolised more rapidly in the periportal hepatocyte compartments. Finally, the pericentral expression of de novo lipogenesis contributed to pericentral steatosis when additionally simulating the increase in sterol-regulatory element binding protein 1c (SREBP-1c) seen in NAFLD patients in vivo. The hepatic triglyceride concentration was predicted to be most sensitive to inter-individual variation in the activity of enzymes which, either directly or indirectly, determine the rate of free fatty acid (FFA) oxidation. The concentration was most strongly dependent on the rate constants for β-oxidation and oxidative phosphorylation. It also showed moderate sensitivity to the rate constants for processes which alter the allosteric inhibition of β-oxidation by acetyl-CoA. The predominant sinusoidal location of steatosis meanwhile was most sensitive variations in the zonation of proteins mediating FFA uptake or triglyceride release as very low density lipoproteins (VLDL). Neither the total hepatic concentration nor the location of steatosis showed strong sensitivity to variations in the lipogenic rate constants. PMID:27632189

  15. A composite model including visfatin, tissue polypeptide-specific antigen, hyaluronic acid, and hematological variables for the diagnosis of moderate-to-severe fibrosis in nonalcoholic fatty liver disease: a preliminary study.

    PubMed

    Chwist, Alina; Hartleb, Marek; Lekstan, Andrzej; Kukla, Michał; Gutkowski, Krzysztof; Kajor, Maciej

    2014-01-01

    Histopathological risk factors for end-stage liver failure in patients with nonalcoholic fatty liver disease (NAFLD) include nonalcoholic steatohepatitis (NASH) and advanced liver fibrosis. There is a need for noninvasive diagnostic methods for these 2 conditions. The aim of this study was to investigate new laboratory variables with a predictive potential to detect advanced fibrosis (stages 2 and 3) in NAFLD. The study involved 70 patients with histologically proven NAFLD of varied severity. Additional laboratory variables included zonulin, haptoglobin, visfatin, adiponectin, leptin, tissue polypeptide-specific antigen (TPSA), hyaluronic acid, and interleukin 6. Patients with NASH (NAFLD activity score of ≥5) had significantly higher HOMA-IR values and serum levels of visfatin, haptoglobin, and zonulin as compared with those without NASH on histological examination. Advanced fibrosis was found in 16 patients (22.9%) and the risk factors associated with its prevalence were age, the ratio of erythrocyte count to red blood cell distribution width, platelet count, and serum levels of visfatin and TPSA. Based on these variables, we constructed a scoring system that differentiated between NAFLD patients with and without advanced fibrosis with a sensitivity of 75% and specificity of 100% (area under the receiver operating characteristic curve, 0.93). The scoring system based on the above variables allows to predict advanced fibrosis with high sensitivity and specificity. However, its clinical utility should be verified in further studies involving a larger number of patients.

  16. Response of fibroblast growth factor 19 and bile acid synthesis after a body weight-adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non-randomized controlled pilot trial.

    PubMed

    Friedrich, Dana; Marschall, Hanns-Ulrich; Lammert, Frank

    2018-06-04

    Non-alcoholic fatty liver disease (NAFLD) is common both in obese and overweight patients. Fibroblast growth factor 19 (FGF19), an intestinal hormone, could play a role in the complex pathogenesis of NAFLD. The aim of our study was to investigate responses of FGF19 and bile acid (BA) synthesis after a body weight-adjusted oral fat tolerance test (OFTT) in overweight and obese NAFLD patients. For this study, we recruited 26 NAFLD patients; 14 overweight (median BMI 28.3 kg/m 2 ), 12 obese (35.3 kg/m 2 ) and 16 healthy controls (24.2 kg/m 2 ). All individuals received 1 g fat (Calogen®) per kg body weight orally. Serum concentrations of FGF19 were determined by ELISA. Concentrations of BAs and BA synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) were measured by gas chromatography-mass spectrometry and high-performance liquid chromatography, respectively; all at 0 (baseline), 2, 4 and 6 h during the OFTT. BMI correlated negatively with fasting FGF19 concentrations (rho = - 0.439, p = 0.004). FGF19 levels of obese NAFLD patients were significantly (p = 0.01) lower in the fasting state (median 116.0 vs. 178.5 pg/ml), whereas overweight NAFLD patients had significantly (p = 0.004) lower FGF19 concentrations 2 h after the fat load (median 163.0 vs. 244.5 pg/ml), and lowest values at all postprandial time points as compared to controls. Baseline BA concentrations correlated positively with FGF19 values (rho = 0.306, p = 0.048). In all groups, we observed BA increases during the OFTT with a peak at 2 h but no change in C4 levels in overweight/obese NAFLD patients. Reduced basal gastrointestinal FGF19 secretion and decreased postprandial response to oral fat together with blunted effect on BA synthesis indicate alterations in intestinal or hepatic FXR signaling in overweight and obese NAFLD subjects. The precise mechanism of FGF19 signaling after oral fat load needs further evaluation. We have registered the trial retrospectively on 30

  17. Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD).

    PubMed

    Ni, Xunjun; Wang, Haiyan

    2016-01-01

    Silymarin, which derived from the milk thistle plant (silybum marianum), has been used for centuries as a natural remedy for diseases of the liver and biliary tract. Considering the therapeutic potential to liver disease, we tested efficacy of silymarin on hepatic steatosis with a high fat diet (HFD)-induced mouse model of non-alcoholic fatty liver disease (NAFLD), and investigated possible effects on lipid metabolic pathways. In our study, silymarin could attenuate the hepatic steatosis, which was proved by both Oil Red O staining and hepatic triglyceride (TG) level determination. Furthermore, compared with INT-747, a potent and selective FXR agonist, silymarin could preserve plasmatic high-density lipoprotein cholesterol (HDL-C) to a higher level and low-density lipoprotein cholesterol (LDL-C) to a lower level, which benefited more to the circulation system. Through real-time PCR analysis, we clarified a vital protective role of silymarin in mRNA regulation of genes involved in lipid metabolism and oxidative stress. It was also shown that silymarin had no effects on body weight, food intake, and liver transaminase. Taken together, silymarin could attenuate hepatic steatosis in a mouse model of NAFLD through regulation of lipid metabolism and oxidative stress, and benefit to the circulation system. All these findings shed new light on NAFLD treatment.

  18. Quantification of hepatic and visceral fat by CT and MR imaging: relevance to the obesity epidemic, metabolic syndrome and NAFLD.

    PubMed

    Graffy, Peter M; Pickhardt, Perry J

    2016-06-01

    Trends in obesity have continued to increase in the developed world over the past few decades, along with related conditions such as metabolic syndrome, which is strongly associated with this epidemic. Novel and innovative methods to assess relevant obesity-related biomarkers are needed to determine the clinical significance, allow for surveillance and intervene if appropriate. Aggregations of specific types of fat, specifically hepatic and visceral adiposity, are now known to be correlated with these conditions, and there are a variety of imaging techniques to identify and quantify their distributions and provide diagnostic information. These methods are particularly salient for metabolic syndrome, which is related to both hepatic and visceral adiposity but currently not defined by it. Simpler non-specific fat measurements, such as body weight, abdominal circumference and body mass index are more frequently used but lack the ability to characterize fat location. In addition, non-alcoholic fatty liver disease (NAFLD) is a related condition that carries relevance not only for obesity-related diseases but also for the progression of the liver-specific disease, including non-alcoholic steatohepatitis and cirrhosis, albeit at a much lower frequency. Recent CT and MRI techniques have emerged to potentially optimize diagnosing metabolic syndrome and NAFLD through non-invasive quantification of visceral fat and hepatic steatosis with high accuracy. These imaging modalities should aid us in further understanding the relationship of hepatic and visceral fat to the obesity-related conditions such as metabolic syndrome, NAFLD and cardiovascular disease.

  19. Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease.

    PubMed

    Pacifico, Lucia; Andreoli, Gian Marco; D'Avanzo, Miriam; De Mitri, Delia; Pierimarchi, Pasquale

    2018-05-21

    Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease (NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome (MetS), like insulin resistance (IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, MetS, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin (OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesity-related comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of MetS as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.

  20. Nursing Activities Score: nursing work load in a burns Intensive Care Unit1

    PubMed Central

    Camuci, Marcia Bernadete; Martins, Júlia Trevisan; Cardeli, Alexandrina Aparecida Maciel; Robazzi, Maria Lúcia do Carmo Cruz

    2014-01-01

    Objective to evaluate the nursing work load in a Burns Intensive Care Unit according to the Nursing Activities Score. Method an exploratory, descriptive cross-sectional study with a quantitative approach. The Nursing Activities Score was used for data collection between October 2011 and May 2012, totalling 1,221 measurements, obtained from 50 patients' hospital records. Data for qualitative variables was described in tables; for the quantitative variables, calculations using statistical measurements were used. Results the mean score for the Nursing Activities Score was 70.4% and the median was 70.3%, corresponding to the percentage of the time spent on direct care to the patient in 24 hours. Conclusion the Nursing Activities Score provided information which involves the process of caring for patients hospitalized in a Burns Intensive Care Unit, and indicated that there is a high work load for the nursing team of the sector studied. PMID:26107842

  1. Development of hepatocellular carcinoma in a murine model of nonalcoholic steatohepatitis induced by use of a high-fat/fructose diet and sedentary lifestyle.

    PubMed

    Dowman, Joanna K; Hopkins, Laurence J; Reynolds, Gary M; Nikolaou, Nikolaos; Armstrong, Matthew J; Shaw, Jean C; Houlihan, Diarmaid D; Lalor, Patricia F; Tomlinson, Jeremy W; Hübscher, Stefan G; Newsome, Philip N

    2014-05-01

    Obesity is increasingly prevalent, strongly associated with nonalcoholic liver disease, and a risk factor for numerous cancers. Here, we describe the liver-related consequences of long-term diet-induced obesity. Mice were exposed to an extended obesity model comprising a diet high in trans-fats and fructose corn syrup concurrent with a sedentary lifestyle. Livers were assessed histologically using the nonalcoholic fatty liver disease (NAFLD) activity score (Kleiner system). Mice in the American Lifestyle-Induced Obesity Syndrome (ALIOS) model developed features of early nonalcoholic steatohepatitis at 6 months (mean NAFLD activity score = 2.4) and features of more advanced nonalcoholic steatohepatitis at 12 months, including liver inflammation and bridging fibrosis (mean NAFLD activity score = 5.0). Hepatic expression of lipid metabolism and insulin signaling genes were increased in ALIOS mice compared with normal chow-fed mice. Progressive activation of the mouse hepatic stem cell niche in response to ALIOS correlated with steatosis, fibrosis, and inflammation. Hepatocellular neoplasms were observed in 6 of 10 ALIOS mice after 12 months. Tumors displayed cytological atypia, absence of biliary epithelia, loss of reticulin, alteration of normal perivenular glutamine synthetase staining (absent or diffuse), and variable α-fetoprotein expression. Notably, perivascular tumor cells expressed hepatic stem cell markers. These studies indicate an adipogenic lifestyle alone is sufficient for the development of nonalcoholic steatohepatitis, hepatic stem cell activation, and hepatocarcinogenesis in wild-type mice. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Development of Hepatocellular Carcinoma in a Murine Model of Nonalcoholic Steatohepatitis Induced by Use of a High-Fat/Fructose Diet and Sedentary Lifestyle

    PubMed Central

    Dowman, Joanna K.; Hopkins, Laurence J.; Reynolds, Gary M.; Nikolaou, Nikolaos; Armstrong, Matthew J.; Shaw, Jean C.; Houlihan, Diarmaid D.; Lalor, Patricia F.; Tomlinson, Jeremy W.; Hübscher, Stefan G.; Newsome, Philip N.

    2014-01-01

    Obesity is increasingly prevalent, strongly associated with nonalcoholic liver disease, and a risk factor for numerous cancers. Here, we describe the liver-related consequences of long-term diet-induced obesity. Mice were exposed to an extended obesity model comprising a diet high in trans-fats and fructose corn syrup concurrent with a sedentary lifestyle. Livers were assessed histologically using the nonalcoholic fatty liver disease (NAFLD) activity score (Kleiner system). Mice in the American Lifestyle-Induced Obesity Syndrome (ALIOS) model developed features of early nonalcoholic steatohepatitis at 6 months (mean NAFLD activity score = 2.4) and features of more advanced nonalcoholic steatohepatitis at 12 months, including liver inflammation and bridging fibrosis (mean NAFLD activity score = 5.0). Hepatic expression of lipid metabolism and insulin signaling genes were increased in ALIOS mice compared with normal chow-fed mice. Progressive activation of the mouse hepatic stem cell niche in response to ALIOS correlated with steatosis, fibrosis, and inflammation. Hepatocellular neoplasms were observed in 6 of 10 ALIOS mice after 12 months. Tumors displayed cytological atypia, absence of biliary epithelia, loss of reticulin, alteration of normal perivenular glutamine synthetase staining (absent or diffuse), and variable α-fetoprotein expression. Notably, perivascular tumor cells expressed hepatic stem cell markers. These studies indicate an adipogenic lifestyle alone is sufficient for the development of nonalcoholic steatohepatitis, hepatic stem cell activation, and hepatocarcinogenesis in wild-type mice. PMID:24650559

  3. A comprehensive review of noninvasive liver fibrosis tests in pediatric nonalcoholic Fatty liver disease.

    PubMed

    Mansoor, Sana; Collyer, Elizabeth; Alkhouri, Naim

    2015-06-01

    Nonalcoholic fatty liver disease (NAFLD) and its spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis have been increasing in the pediatric population. The presence and severity of fibrosis in patients with NAFLD are important prognostic factors for the risk of disease progression to cirrhosis. The gold standard for staging liver fibrosis is a liver biopsy. However, given the risks of this procedure, especially in the pediatric population, the development of noninvasive markers to diagnose and monitor progression of NAFLD is desirable. This paper will review recently developed noninvasive methods for diagnosing liver fibrosis in children with NAFLD. These include simple fibrosis scores, advanced biochemical markers, and radiologic imaging studies. Simple fibrosis scores use readily available laboratory tests; available one include AST/ALT ratio, AST to platelet ratio index (APRI), fibrosis (FIB)-4 index, NAFLD fibrosis score (NFS), pediatric NAFLD fibrosis index (PNFI), and pediatric NALFD fibrosis score (PNFS). Advanced biochemical markers include biomarkers of hepatocyte cell death such as cytokeratin 18 fragment levels, and markers of extracellular matrix turnover such as the Enhanced Liver Fibrosis (ELF) test and hyaluronic acid. Radiologic imaging studies estimate liver stiffness as a surrogate for liver fibrosis; these include transient elastography (TE), magnetic resonance elastography (MRE), and acoustic radiation force impulse imaging (ARFI).

  4. Schizotypal Perceptual Aberrations of Time: Correlation between Score, Behavior and Brain Activity

    PubMed Central

    Arzy, Shahar; Mohr, Christine; Molnar-Szakacs, Istvan; Blanke, Olaf

    2011-01-01

    A fundamental trait of the human self is its continuum experience of space and time. Perceptual aberrations of this spatial and temporal continuity is a major characteristic of schizophrenia spectrum disturbances – including schizophrenia, schizotypal personality disorder and schizotypy. We have previously found the classical Perceptual Aberration Scale (PAS) scores, related to body and space, to be positively correlated with both behavior and temporo-parietal activation in healthy participants performing a task involving self-projection in space. However, not much is known about the relationship between temporal perceptual aberration, behavior and brain activity. To this aim, we composed a temporal Perceptual Aberration Scale (tPAS) similar to the traditional PAS. Testing on 170 participants suggested similar performance for PAS and tPAS. We then correlated tPAS and PAS scores to participants' performance and neural activity in a task of self-projection in time. tPAS scores correlated positively with reaction times across task conditions, as did PAS scores. Evoked potential mapping and electrical neuroimaging showed self-projection in time to recruit a network of brain regions at the left anterior temporal cortex, right temporo-parietal junction, and occipito-temporal cortex, and duration of activation in this network positively correlated with tPAS and PAS scores. These data demonstrate that schizotypal perceptual aberrations of both time and space, as reflected by tPAS and PAS scores, are positively correlated with performance and brain activation during self-projection in time in healthy individuals along the schizophrenia spectrum. PMID:21267456

  5. Spleen dimensions are inversely associated with lysosomal acid lipase activity in patients with non-alcoholic fatty liver disease.

    PubMed

    Polimeni, Licia; Pastori, Daniele; Baratta, Francesco; Tozzi, Giulia; Novo, Marta; Vicinanza, Roberto; Troisi, Giovanni; Pannitteri, Gaetano; Ceci, Fabrizio; Scardella, Laura; Violi, Francesco; Angelico, Francesco; Del Ben, Maria

    2017-12-01

    Fatty liver and splenomegaly are typical features of genetic lysosomal acid lipase (LAL) deficiency. No data in adult patients with non-genetic reduction of LAL activity are available. We investigate the association between spleen dimensions and LAL activity in non-alcoholic fatty liver disease (NAFLD) patients, in whom a reduced LAL activity has been reported. We include 425 consecutive patients who underwent abdominal ultrasound to evaluate hepatic steatosis and spleen dimensions. LAL activity was measured with dried blood spot method (Lalistat2). NAFLD was present in 74.1% of screened patients. Higher median spleen longitudinal diameter (10.6 vs. 9.9 cm; p < 0.001) and spleen area (SA) (32.7 vs. 27.7 cm 2 ; p < 0.001), together with a higher and proportion of splenomegaly (17.8 vs. 5.5%, p = 0.001), are present in patients with NAFLD compared to those without. In NAFLD patients, median LAL activity is 0.9 nmol/spot/h. LAL activity is lower in 56 patients with splenomegaly, as compared to those without (p = 0.009). At multivariable logistic regression analysis, age (above median, OR 0.344; p = 0.003), LAL activity (below median, OR 2.206, p = 0.028), and platelets (OR 0.101, p = 0.002) are significantly associated with splenomegaly. NAFLD patients disclose a relatively high prevalence of spleen enlargement and splenomegaly, which are significantly associated with a reduced LAL activity, suggesting that LAL may contribute to spleen enlargement in this setting.

  6. Application of Weka environment to determine factors that stand behind non-alcoholic fatty liver disease (NAFLD)

    NASA Astrophysics Data System (ADS)

    Plutecki, Michal M.; Wierzbicka, Aldona; Socha, Piotr; Mulawka, Jan J.

    2009-06-01

    The paper describes an innovative approach to discover new knowledge in non-alcoholic fatty liver disease (NAFLD). In order to determine the factors that may cause the disease a number of classification and attribute selection algorithms have been applied. Only those with the best classification results were chosen. Several interesting facts associated with this unclear disease have been discovered. All data mining computations were made in Weka environment.

  7. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults.

    PubMed

    Chen, Yu-ming; Liu, Yan; Zhou, Rui-fen; Chen, Xiao-ling; Wang, Cheng; Tan, Xu-ying; Wang, Li-jun; Zheng, Rui-dan; Zhang, Hong-wei; Ling, Wen-hua; Zhu, Hui-lian

    2016-01-08

    Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18-60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants.

  8. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults

    PubMed Central

    Chen, Yu-ming; Liu, Yan; Zhou, Rui-fen; Chen, Xiao-ling; Wang, Cheng; Tan, Xu-ying; Wang, Li-jun; Zheng, Rui-dan; Zhang, Hong-wei; Ling, Wen-hua; Zhu, Hui-lian

    2016-01-01

    Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18–60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants. PMID:26743949

  9. Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B.

    PubMed

    Pan, Qin; Zhang, Rui-Nan; Wang, Yu-Qin; Zheng, Rui-Dan; Mi, Yu-Qiang; Liu, Wen-Bin; Shen, Feng; Chen, Guang-Yu; Lu, Jia-Fa; Zhu, Chan-Yan; Zhang, Shu-Yi; Chen, Yi-Ming; Sun, Wan-Lu; Fan, Jian-Gao

    2015-07-28

    To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD). A cohort of Han patients with biopsy-proven CHB, with or without NAFLD (CHB group, n = 51; CHB + NAFLD group, n = 57), and normal controls (normal group, n = 47) were recruited from Northern (Tianjin), Central (Shanghai), and Southern (Zhangzhou) China. Their PNPLA3 polymorphisms were genotyped by gene sequencing. The association between PNPLA3 polymorphisms and susceptibility to NAFLD, and clinical characteristics of NAFLD were evaluated on the basis of physical indices, liver function tests, glycolipid metabolism, and histopathologic scoring. The association of PNPLA3 polymorphisms and hepatitis B virus (HBV) load was determined by the serum level of HBV DNA. After adjusting for age, sex, and body mass index, we found that four linked single nucleotide polymorphisms (SNPs) of PNPLA3, including the rs738409 G allele (CHB + NAFLD group vs CHB group: odds ratio [OR] = 2.77, 95% confidence interval [CI]: 1.18-6.54; P = 0.02), rs3747206 T allele (CHB + NAFLD group vs CHB group: OR = 2.77, 95%CI: 1.18-6.54; P = 0.02), rs4823173 A allele (CHB + NAFLD group vs CHB group: OR = 2.73, 95%CI: 1.16-6.44; P = 0.02), and rs2072906 G allele (CHB + NAFLD group vs CHB group: OR = 3.05, 95%CI: 1.28-7.26; P = 0.01), conferred high risk to NAFLD in CHB patients. In patients with both CHB and NAFLD, these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis (NASH) (NAFLD activity score ≥ 3; P = 0.01-0.03) and liver fibrosis (> 1 Metavir grading; P = 0.01-0.04). As compared to those with C/C and C/G at rs738409, C/C and C/T at rs3747206, G/G and G/A at rs4823173, and A/A and A/G at rs2072906, patients in the CHB + NAFLD group with G/G at rs738409, T/T at rs3747206, A/A at rs4823173, and G/G at rs2072906 showed significantly lower serum levels of HBV DNA (P < 0.01-0.05). Four linked

  10. Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B

    PubMed Central

    Pan, Qin; Zhang, Rui-Nan; Wang, Yu-Qin; Zheng, Rui-Dan; Mi, Yu-Qiang; Liu, Wen-Bin; Shen, Feng; Chen, Guang-Yu; Lu, Jia-Fa; Zhu, Chan-Yan; Zhang, Shu-Yi; Chen, Yi-Ming; Sun, Wan-Lu; Fan, Jian-Gao

    2015-01-01

    AIM: To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD). METHODS: A cohort of Han patients with biopsy-proven CHB, with or without NAFLD (CHB group, n = 51; CHB + NAFLD group, n = 57), and normal controls (normal group, n = 47) were recruited from Northern (Tianjin), Central (Shanghai), and Southern (Zhangzhou) China. Their PNPLA3 polymorphisms were genotyped by gene sequencing. The association between PNPLA3 polymorphisms and susceptibility to NAFLD, and clinical characteristics of NAFLD were evaluated on the basis of physical indices, liver function tests, glycolipid metabolism, and histopathologic scoring. The association of PNPLA3 polymorphisms and hepatitis B virus (HBV) load was determined by the serum level of HBV DNA. RESULTS: After adjusting for age, sex, and body mass index, we found that four linked single nucleotide polymorphisms (SNPs) of PNPLA3, including the rs738409 G allele (CHB + NAFLD group vs CHB group: odds ratio [OR] = 2.77, 95% confidence interval [CI]: 1.18-6.54; P = 0.02), rs3747206 T allele (CHB + NAFLD group vs CHB group: OR = 2.77, 95%CI: 1.18-6.54; P = 0.02), rs4823173 A allele (CHB + NAFLD group vs CHB group: OR = 2.73, 95%CI: 1.16-6.44; P = 0.02), and rs2072906 G allele (CHB + NAFLD group vs CHB group: OR = 3.05, 95%CI: 1.28-7.26; P = 0.01), conferred high risk to NAFLD in CHB patients. In patients with both CHB and NAFLD, these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis (NASH) (NAFLD activity score ≥ 3; P = 0.01-0.03) and liver fibrosis (> 1 Metavir grading; P = 0.01-0.04). As compared to those with C/C and C/G at rs738409, C/C and C/T at rs3747206, G/G and G/A at rs4823173, and A/A and A/G at rs2072906, patients in the CHB + NAFLD group with G/G at rs738409, T/T at rs3747206, A/A at rs4823173, and G/G at rs2072906 showed significantly lower serum levels of HBV DNA (P < 0

  11. High FIB-4 index as an independent risk factor of prevalent chronic kidney disease in patients with nonalcoholic fatty liver disease.

    PubMed

    Xu, Huang-Wei; Hsu, Yung-Chien; Chang, Chia-Hao; Wei, Kuo-Liang; Lin, Chun-Liang

    2016-03-01

    Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is linked to an increased risk for chronic kidney disease (CKD); liver fibrosis with biopsy-proven NAFLD has also been shown to associate with an increased risk of CKD. This study compares the diagnostic performance of simple noninvasive tests in identifying prevalent CKD among individuals with ultrasonography-diagnosed NAFLD. A total of 755 with ultrasonography-diagnosed NAFLD were included. Estimated glomerular filtration rate and noninvasive markers for hepatic fibrosis: aspartate transaminase to alanine transaminase ratio (AAR), aspartate transaminase to platelet ratio index (APRI), FIB-4 score, NAFLD fibrosis score (NFS) and BARD score were assessed. Binary logistic regression to generate a propensity score and receiver operating characteristic curves were developed for each of the noninvasive markers for predicting CKD, and the area under the receiver operating characteristic curve was greatest for FIB-4 score (0.750), followed by NFS (0.710), AAR (0.594), APRI (0.587), and BARD score (0.561). A cut-off value of 1.100 for FIB-4 score gave a sensitivity of 68.85% and a specificity of 71.07% for predicting CKD. The positive predictive value and negative predictive value were 37.50 and 90.05%, respectively. In multiple logistic regression analysis, only FIB-4 score ≧1.100 (OR 2.660, 95% CI 1.201-5.889; p = .016), older age, higher diastolic blood pressure and higher uric acid were independent predictors of CKD. High noninvasive fibrosis score is associated with an increased risk of prevalent CKD; the FIB-4 is the better predictor. With a cut-off value of 1.100 for FIB-4, it is useful in excluding the presence of CKD in patients with NAFLD.

  12. Association between physical activity and risk of nonalcoholic fatty liver disease: a meta-analysis.

    PubMed

    Qiu, Shanhu; Cai, Xue; Sun, Zilin; Li, Ling; Zügel, Martina; Steinacker, Jürgen Michael; Schumann, Uwe

    2017-09-01

    Increased physical activity (PA) is a key element in the management of patients with nonalcoholic fatty liver disease (NAFLD); however, its association with NAFLD risk has not been systematically assessed. This meta-analysis of observational studies was to quantify this association with dose-response analysis. Electronic databases were searched to January 2017 for studies of adults reporting the risk of NAFLD in relation to PA with cohort or case-control designs. Studies that reported sex-specific data were included as separate studies. The overall risk estimates were pooled using a random-effects model, and the dose-response analysis was conducted to shape the quantitative relationship. A total of 6 cohort studies from 5 articles with 32,657 incident NAFLD cases from 142,781 participants, and 4 case-control studies from 3 articles with 382 NAFLD cases and 302 controls were included. Compared with the lowest PA level, the highest PA level was associated with a risk reduction of NAFLD in cohort [RR (risk ratio) 0.79, 95% CI (confidence interval) 0.71-0.89] and case-control studies [OR (odds ratio) 0.43, 95% CI 0.27-0.68]. For cohort studies, both highest and moderate PA levels were superior to the light one in lowering NAFLD risk ( p for interaction = 0.006 and 0.02, respectively), and there was a log-linear dose-response association ( p for nonlinearity = 0.10) between PA and NAFLD risk [RR 0.82 (95% CI 0.73-0.91) for every 500 metabolic equivalent (MET)-minutes/week increment in PA]. Increased PA may lead to a reduced risk of NAFLD in a dose-dependent manner, and the current guideline-recommended minimum PA level that approximates to 500 MET-minutes/week is able to moderately reduce the NAFLD risk.

  13. Longitudinal associations between physical activity and depression scores in Swedish women followed 32 years.

    PubMed

    Gudmundsson, P; Lindwall, M; Gustafson, D R; Östling, S; Hällström, T; Waern, M; Skoog, I

    2015-12-01

    Physical activity is negatively associated with depressive symptoms. However, few studies consider dynamic associations of changes in physical activity and reciprocal relationships. This study aimed to perform comprehensive evaluations of relationships between physical activity and depression scores in women followed from mid- to late life. The Prospective Population Study of Women in Gothenburg, Sweden, provided repeated measures of self-reported physical activity and depressive symptoms between 1974 and 2005 (baseline N = 676, 84.5% response rate). Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale, and physical activity was evaluated by the Saltin-Grimby Physical Activity Level Scale. Latent growth curve analyses were used to evaluate associations of change, and cross-lagged models were used to study the reciprocal relationship between physical activity and depression scores. At baseline, lower levels of physical activity were related to higher depression scores. Individuals with decreasing physical activity over time evidenced higher depression scores at 32-year follow-up. Higher average baseline depression score was related to declining levels of physical activity at subsequent examinations. Reduced physical activity may be a long-term consequence of depression. It is important to address individual changes in physical activity and not merely absolute levels of physical activity in relationship to depression. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study.

    PubMed

    Krawczyk, Marcin; Rau, Monika; Schattenberg, Jörn M; Bantel, Heike; Pathil, Anita; Demir, Münevver; Kluwe, Johannes; Boettler, Tobias; Lammert, Frank; Geier, Andreas

    2017-01-01

    The PNPLA3 p.I148M, TM6SF2 p.E167K, and MBOAT7 rs641738 variants represent genetic risk factors for nonalcoholic fatty liver disease (NAFLD). Here we investigate if these polymorphisms modulate both steatosis and fibrosis in patients with NAFLD. We recruited 515 patients with NAFLD (age 16-88 years, 280 female patients). Liver biopsies were performed in 320 patients. PCR-based assays were used to genotype the PNPLA3, TM6SF2, and MBOAT7 variants. Carriers of the PNPLA3 and TM6SF2 risk alleles showed increased serum aspartate aminotransferase and alanine transaminase activities (P < 0.05). The PNPLA3 genotype was associated with steatosis grades S2-S3 (P < 0.001) and fibrosis stages F2-F4 (P < 0.001). The TM6SF2 genotype was associated with steatosis (P = 0.003) but not with fibrosis (P > 0.05). The MBOAT7 variant was solely associated with increased fibrosis (P = 0.046). In the multivariate model, variants PNPLA3 (P = 0.004) and TM6SF2 (P = 0.038) were associated with steatosis. Fibrosis stages were affected by the PNPLA3 (P = 0.042) and MBOAT7 (P = 0.021) but not by the TM6SF2 polymorphism (P > 0.05). The PNPLA3, TM6SF2, and MBOAT7 variants are associated with increased liver injury. The TM6SF2 variant seems to modulate predominantly hepatic fat accumulation, whereas the MBOAT7 polymorphism is linked to fibrosis. The PNPLA3 polymorphism confers risk of both increased steatosis and fibrosis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  15. Methodological issues in the design of a rheumatoid arthritis activity score and its cut-offs.

    PubMed

    Collignon, Olivier

    2014-01-01

    Activity of rheumatoid arthritis (RA) can be evaluated using several scoring scales based on clinical features. The most widely used one is the Disease Activity Score involving 28 joint counts (DAS28) for which cut-offs were proposed to help physicians classify patients. However, inaccurate scoring can lead to inappropriate medical decisions. In this article some methodological issues in the design of such a score and its cut-offs are highlighted in order to further propose a strategy to overcome them. As long as the issues reviewed in this article are not addressed, results of studies based on standard disease activity scores such as DAS28 should be considered with caution.

  16. [Frequency of NAFLD in a group of patients with metabolic syndrome in Veracruz, Mexico].

    PubMed

    Roesch-Dietlen, Federico; Dorantes-Cuéllar, Alicia; Carrillo-Toledo, Maria Graciela; Martínez-Sibaja, Cristina; Rojas-Carrera, Sonia; Bonilla-Rojas, Q C Sashenka; Uchino-Higueras, Virginia; Lagunas, Teresa; Carrasco-Arróniz, Miguel Angel; Soler-Leal, Bertha; León-Valdivieso, Johnatan; Cid-Juárez, Silvia; Martínez, José Angel

    2006-01-01

    values and aminotransferases in obese and diabetic patients compared with normal subjects and overweight patients in our study, the USG did not show sensibility and specificity to detect Non alcoholic fatty liver disease (NAFLD). The results of this study show a lower frequency compared with the rest of the world, however it was higher in diabetic population than the frequency published by Bernal in Hidalgo, Mexico. The aminotransferases level resulted elevated in all patients with metabolic syndrome and NAFLD so we consider that elevated aminotransferases levels is the best predictor to suspect the presence of NAFLD. That is why it's very important to consider the possibility to avoid the progression to cirrhosis and hepatocarcinoma.

  17. Activated carbon N-acetylcysteine microcapsule protects against nonalcoholic fatty liver disease in young rats via activating telomerase and inhibiting apoptosis

    PubMed Central

    Zhou, Hongping; Xi, Jianjun; Sun, Jingjing; Ke, Yunling; Zhang, Jiankang; Shao, Yidan; Jiang, Xiaojie; Pan, Xuwang; Liu, Shourong; Zhuang, Rangxiao

    2018-01-01

    Non-alcoholic fatty liver disease (NAFLD) is becoming one of the world's most common chronic liver diseases in childhood, yet no therapy is available that has been approved by the food and drug administration (FDA). Previous studies have reported that telomere and telomerase are involved the development and progression of NAFLD. This study was designed to investigate the potential beneficial effects of activated carbon N-acetylcysteine (ACNAC) microcapsules on the development of NAFLD in young rats as well as the underlying mechanism(s) involved. Three-week old male Sprague Dawley rats were given high-fat diet (HFD) with/without ACNAC treatment for 7 consecutive weeks. Liver pathologies were determined by hematoxylin and eosin (H&E) and Oil Red O staining, as well as by changes in biochemical parameters of plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, respectively. Glucose homeostasis was evaluated by the glucose tolerance test and the liver telomere length and activity were measured by real time PCR and telomeric repeat amplification protocol (TRAP). Western blot analysis was performed to determine the expression level of Bcl-2, Bax and Caspase-3. Our results demonstrated that ACNAC supplementation improved liver pathologies of rats that received long-term HFD feeding. ACNAC supplementation prevented HFD-induced telomere shortening and improved telomerase activity. Moreover, in comparison to HFD-fed rats, ACNAC supplementation markedly increased the expression of Bcl-2, but significantly decreased the expression of Bax and Caspase-3 in juvenile rats. Together, these results indicate that ACNAC may be a promising choice for preventing and treating NAFLD among children. PMID:29324774

  18. Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study1[S

    PubMed Central

    Krawczyk, Marcin; Rau, Monika; Schattenberg, Jörn M.; Bantel, Heike; Pathil, Anita; Demir, Münevver; Kluwe, Johannes; Boettler, Tobias; Lammert, Frank; Geier, Andreas

    2017-01-01

    The PNPLA3 p.I148M, TM6SF2 p.E167K, and MBOAT7 rs641738 variants represent genetic risk factors for nonalcoholic fatty liver disease (NAFLD). Here we investigate if these polymorphisms modulate both steatosis and fibrosis in patients with NAFLD. We recruited 515 patients with NAFLD (age 16–88 years, 280 female patients). Liver biopsies were performed in 320 patients. PCR-based assays were used to genotype the PNPLA3, TM6SF2, and MBOAT7 variants. Carriers of the PNPLA3 and TM6SF2 risk alleles showed increased serum aspartate aminotransferase and alanine transaminase activities (P < 0.05). The PNPLA3 genotype was associated with steatosis grades S2–S3 (P < 0.001) and fibrosis stages F2–F4 (P < 0.001). The TM6SF2 genotype was associated with steatosis (P = 0.003) but not with fibrosis (P > 0.05). The MBOAT7 variant was solely associated with increased fibrosis (P = 0.046). In the multivariate model, variants PNPLA3 (P = 0.004) and TM6SF2 (P = 0.038) were associated with steatosis. Fibrosis stages were affected by the PNPLA3 (P = 0.042) and MBOAT7 (P = 0.021) but not by the TM6SF2 polymorphism (P > 0.05). The PNPLA3, TM6SF2, and MBOAT7 variants are associated with increased liver injury. The TM6SF2 variant seems to modulate predominantly hepatic fat accumulation, whereas the MBOAT7 polymorphism is linked to fibrosis. The PNPLA3 polymorphism confers risk of both increased steatosis and fibrosis. PMID:27836992

  19. [Inter-rater concordance of the "Nursing Activities Score" in intensive care].

    PubMed

    Valls-Matarín, Josefa; Salamero-Amorós, Maria; Roldán-Gil, Carmen; Quintana-Riera, Salvador

    2015-01-01

    To evaluate inter-rater concordance in the valuation of the "Nursing Activities Score". Cross-sectional descriptive study conducted from December 2012 until June 2013 in a general intensive care unit with twelve beds. Three evaluator nurses, simultaneously and independently, through the patient daily charts, scored the nursing workload using Nursing Activities Score scale in all patients admitted over 18 years old. Three hundreds and thirty-nine records were collected. The intra-class correlation coefficient (ICC) between evaluators was 0.92 (0.89-0.94). A perfect concordance was obtained in 39.1% of the items, with 52.2% having a high, and 8.7% having lower concordance, corresponding to two of the items with multiple scoring options. Significant differences between two of the evaluators (P=.049) were found. Although the inter-rater concordance was high, more accurate records are needed to reduce the variability of the items with multiple options and to allow more accuracy in the interpretation and measurement of the data regarding nursing workload. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  20. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.

    PubMed

    Kowdley, Kris V; Belt, Patricia; Wilson, Laura A; Yeh, Matthew M; Neuschwander-Tetri, Brent A; Chalasani, Naga; Sanyal, Arun J; Nelson, James E

    2012-01-01

    Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis. Copyright © 2011 American Association for the Study of Liver Diseases.

  1. Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid.

    PubMed

    Yoo, Wonbeak; Gjuka, Donjeta; Stevenson, Heather L; Song, Xiaoling; Shen, Hong; Yoo, Suk Young; Wang, Jing; Fallon, Michael; Ioannou, George N; Harrison, Stephen A; Beretta, Laura

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NASH, we analyzed two independent NAFLD patient cohorts and used the methionine- and choline-deficient diet (MCD) NASH mouse model. We identified six fatty acids that could serve as non-invasive markers of NASH in patients with NAFLD. Serum levels of 15:0, 17:0 and 16:1n7t negatively correlated with NAFLD activity scores and hepatocyte ballooning scores, while 18:1n7c serum levels strongly correlated with fibrosis stage and liver inflammation. Serum levels of 15:0 and 17:0 also negatively correlated with fasting glucose and AST, while 16:1n7c and 18:1n7c levels positively correlated with AST and ferritin, respectively. Inclusion of demographic and clinical parameters improved the performance of the fatty acid panels in detecting NASH in NAFLD patients. The panel [15:0, 16:1n7t, 18:1n7c, 22:5n3, age, ferritin and APRI] predicted intermediate or advanced fibrosis in NAFLD patients, with 82% sensitivity at 90% specificity [AUROC = 0.92]. 15:0 and 18:1n7c were further selected for functional studies in vivo. Mice treated with 15:0-supplemented MCD diet showed reduced AST levels and hepatic infiltration of ceroid-laden macrophages compared to MCD-treated mice, suggesting that 15:0 deficiency contributes to liver injury in NASH. In contrast, 18:1n7c-supplemented MCD diet didn't affect liver pathology. In conclusion, 15:0 may serve as a promising biomarker or therapeutic target in NASH, opening avenues for the integration of diagnosis and treatment.

  2. Liver and Cardiovascular Damage in Patients With Lean Nonalcoholic Fatty Liver Disease, and Association With Visceral Obesity.

    PubMed

    Fracanzani, Anna Ludovica; Petta, Salvatore; Lombardi, Rosa; Pisano, Giuseppina; Russello, Maurizio; Consonni, Dario; Di Marco, Vito; Cammà, Calogero; Mensi, Laura; Dongiovanni, Paola; Valenti, Luca; Craxì, Antonio; Fargion, Silvia

    2017-10-01

    age, 49 ± 12 y). Significantly lower proportions of patients with lean NAFLD had NASH (17% vs 40% of obese or overweight patients with NAFLD; P = .0001), fibrosis of F2 or higher (17% vs 42%; P = .0001), or carotid plaques (27% vs 39%; P = .03). Patients with lean NAFLD had significantly thinner carotid intima-media (0.74 ± 0.1 mm) than obese or overweight patients with NAFLD (0.84 ± 0.3 mm; P = .0001). There was no significant difference in the proportions of patients with rs738409 C>G in PNPLA3, but a significantly greater proportion of patients with lean NAFLD carried rs58542926 C>T in TM6SF2 (4%) than obese or overweight individuals with NAFLD (0.3%; P = .001). Of the 143 patients with lean NAFLD, 27 had grade 3 steatosis, 24 had a lobular inflammation score greater than 2, 10 had a ballooning score of 2, and 25 had a fibrosis score of 2 or higher. In patients with lean NAFLD, the only variable associated independently with NASH and a fibrosis score of 2 or higher was rs738409 C>G in PNPLA3. Patients with lean NAFLD and a medium waist circumference had a significantly higher risk of diabetes (odds ratio, 11; 95% confidence interval [CI], 1.2-106; P = .03) than overweight or obese patients with a similar waist circumference (odds ratio, 1.3; 95% CI, 0.4-4.2; P = .6). Lean and overweight or obese patients with high waist circumferences had significant increases in risk compared with patients with low and medium circumference and diabetes, hypertension, and fibrosis scores of 2 or higher. In a retrospective study of patients with lean NAFLD vs obese or overweight persons with NAFLD, we found 20% of patients with lean NAFLD to have NASH, fibrosis scores of 2 or higher, and carotid atherosclerosis. Lean patients with rs738409 C>G in PNPLA3 should be monitored for liver disease progression; studies including large series of patients with lean NAFLD will clarify the possible role of TM6SF2 polymorphisms. Copyright © 2017. Published by Elsevier Inc.

  3. Using the EZ-Diffusion Model to Score a Single-Category Implicit Association Test of Physical Activity

    PubMed Central

    Rebar, Amanda L.; Ram, Nilam; Conroy, David E.

    2014-01-01

    Objective The Single-Category Implicit Association Test (SC-IAT) has been used as a method for assessing automatic evaluations of physical activity, but measurement artifact or consciously-held attitudes could be confounding the outcome scores of these measures. The objective of these two studies was to address these measurement concerns by testing the validity of a novel SC-IAT scoring technique. Design Study 1 was a cross-sectional study, and study 2 was a prospective study. Method In study 1, undergraduate students (N = 104) completed SC-IATs for physical activity, flowers, and sedentary behavior. In study 2, undergraduate students (N = 91) completed a SC-IAT for physical activity, self-reported affective and instrumental attitudes toward physical activity, physical activity intentions, and wore an accelerometer for two weeks. The EZ-diffusion model was used to decompose the SC-IAT into three process component scores including the information processing efficiency score. Results In study 1, a series of structural equation model comparisons revealed that the information processing score did not share variability across distinct SC-IATs, suggesting it does not represent systematic measurement artifact. In study 2, the information processing efficiency score was shown to be unrelated to self-reported affective and instrumental attitudes toward physical activity, and positively related to physical activity behavior, above and beyond the traditional D-score of the SC-IAT. Conclusions The information processing efficiency score is a valid measure of automatic evaluations of physical activity. PMID:25484621

  4. Association between liver fibrosis and coronary heart disease risk in patients with nonalcoholic fatty liver disease.

    PubMed

    Dogan, Serkan; Celikbilek, Mehmet; Yilmaz, Yunus K; Sarikaya, Savas; Zararsiz, Gokmen; Serin, Halil I; Borekci, Elif; Akyol, Lütfi; Pirti, Ilyas; Davarci, Sena E

    2015-03-01

    Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as the most common cause of chronic liver disease worldwide. It has been shown that NAFLD in adults is associated with increased risk of coronary heart disease (CHD). Because of the limitations of liver biopsy, noninvasive scoring indexes such as the NAFLD fibrosis score (NFS) were developed. The Framingham risk score (FRS) provides an estimate of CHD risk. In our study we aimed to investigate whether the severity of liver fibrosis estimated with the NFS is associated with a higher risk of CHD among individuals with ultrasonography-diagnosed NAFLD. A total of 155 patients and controls (81 patients with NAFLD and 74 controls) with ages ranging from 18 to 70 years were enrolled in this cross-sectional prospective study. Demographic, anthropometric, clinical, and laboratory data were obtained from each individual. The NAFLD patients were divided into subgroups on the basis of the severity of fatty liver. The FRS and NFS were adopted to predict the risk of CHD and the severity of hepatic fibrosis. In our study, we found that the FRS was higher in NAFLD patients than in controls (P<0.05). According to the FRS category, NFSs were higher in the intermediate/high probability CHD risk group in NAFLD (P<0.05). In multiple models, only age, sex, cholesterol, and HDL were independently associated with intermediate/high CHD risk (P<0.05). We also found a positive correlation between the NFS and the FRS (r=0.373, P<0.001). The optimum NFS cutoff point for identifying intermediate/high CHD risk in NAFLD patients was -2.1284, with a sensitivity and specificity of 95.20 and 48.30%, respectively. The predictive performance of the NFS in the determination of intermediate/high CHD risk in NAFLD patients was found to be 72% based on the area under the curve value. The FRS is associated with the NFS in NAFLD. The assessment of liver fibrosis may be useful for the risk stratification of CHD in the absence of liver

  5. Effects of the new thiazolidine derivative LPSF/GQ-02 on hepatic lipid metabolism pathways in non-alcoholic fatty liver disease (NAFLD).

    PubMed

    Araújo, Shyrlene; Soares E Silva, Amanda; Gomes, Fabiana; Ribeiro, Edlene; Oliveira, Wilma; Oliveira, Amanda; Lima, Ingrid; Lima, Maria do Carmo; Pitta, Ivan; Peixoto, Christina

    2016-10-05

    Non-alcoholic fatty liver disease (NAFLD) is considered the most common manifestation of metabolic syndrome. One of its most important features is the accumulation of triglycerides in the hepatocyte cells. Thiazolidinediones (TZDs) act as insulin sensitizers and are used to treat patients with type 2 diabetes and other conditions that are resistant to insulin, such as hepatic steatosis. Controversially, TZDs are also associated with the development of cardiovascular events and liver problems. For this reason, new therapeutic strategies are necessary to improve liver function in patients with chronic liver diseases. The aim of the present study was to evaluate the effects of LPSF/GQ-02 on the liver lipid metabolism in a murine model of NAFLD. Eighty male LDLR-/- mice were divided into 3 groups: 1-fed with a high-fat diet (HFD); 2-HFD+Pioglitazone (20mg/kg/day); 3-HFD+LPSF/GQ-02 (30mg/kg/day). The experiments lasted 12 weeks and drugs were administered daily by gavage in the final four weeks. The liver was processed for optical microscopy, Oil Red O, immunohistochemistry, immunofluorescence and western blot analysis. LPSF/GQ-02 effectively decreased fat accumulation, increased the hepatic levels of p-AMPK, FoxO1, ATGL, p-ACC and PPARα, and reduced the expression of LXRα, SREBP-1c and ACC. These results suggest that LPSF/GQ-02 acts directly on the hepatic lipid metabolism through the activation of the PPAR-α/AMPK/FoxO1/ATGL lipolytic pathway, and the inhibition of the AMPK/LXR/SREBP-1c/ACC/FAS lipogenic pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. PNPLA3 as a Genetic Determinant of Risk for and Severity of Non-alcoholic Fatty Liver Disease Spectrum.

    PubMed

    Salameh, Habeeb; Hanayneh, Muhannad Al; Masadeh, Maen; Naseemuddin, Mohammed; Matin, Tasnia; Erwin, Angelika; Singal, Ashwani K

    2016-09-28

    Background and Aims: Patatin-like phospholipase domain protein 3 ( PNPLA3 ) polymorphisms ( rs738409 C>G) are associated with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to examine the association of PNPLA3 polymorphisms with the spectrum and severity of this disease. Methods: Studies evaluating the association between the PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) and NAFLD were included. Pooled data are reported as odds ratios (ORs) with 95% confidence intervals. Results: Of 393 potentially relevant studies, 35 on NAFLD were included in the analysis. Compared to healthy controls, the pooled ORs for rs738409 CG and GG compared to CC among patients with non-alcoholic fatty liver (NAFL) were 1.46 (1.16-1.85) and 2.76 (2.30-3.13), and were 1.75 (1.24-2.46) and 4.44 (2.92-6.76) among patients with non-alcoholic steatohepatitis respectively. The respective ORs for CG and GG compared to the CC genotype were 2.35 (0.90-6.13) and 5.05 (1.47-17.29) when comparing non-alcoholic hepatocellular carcinoma to NAFL patients. Among the NAFLD patients, the ORs for G allele frequency when comparing steatosis grade 2-3 to grade 0-1 NAFL, when comparing the NAFLD activity score of ≥ 4 to score ≤ 3, when comparing NASH to NAFLD, when comparing the presence of lobular inflammation to absence, and when comparing the presence of hepatocyte ballooning to absence were 2.33 (1.43-3.80), 1.80 (1.36-2.37), 1.66 (1.42-1.94), 1.58 (1.19-2.10), and 2.63 (1.87-3.69) respectively. Subgroup analysis based on ethnicity showed similar results. Conclusions: PNPLA3 polymorphisms have strong association with the risk for and severity of NAFLDs. PNPLA3 polymorphism plays an evolving role in diagnosis and treatment decisions in patients with NAFLD.

  7. PNPLA3 as a Genetic Determinant of Risk for and Severity of Non-alcoholic Fatty Liver Disease Spectrum

    PubMed Central

    Salameh, Habeeb; Hanayneh, Muhannad Al; Masadeh, Maen; Naseemuddin, Mohammed; Matin, Tasnia; Erwin, Angelika; Singal, Ashwani K.

    2016-01-01

    Abstract Background and Aims: Patatin-like phospholipase domain protein 3 (PNPLA3) polymorphisms (rs738409 C>G) are associated with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to examine the association of PNPLA3 polymorphisms with the spectrum and severity of this disease. Methods: Studies evaluating the association between the PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) and NAFLD were included. Pooled data are reported as odds ratios (ORs) with 95% confidence intervals. Results: Of 393 potentially relevant studies, 35 on NAFLD were included in the analysis. Compared to healthy controls, the pooled ORs for rs738409 CG and GG compared to CC among patients with non-alcoholic fatty liver (NAFL) were 1.46 (1.16–1.85) and 2.76 (2.30–3.13), and were 1.75 (1.24–2.46) and 4.44 (2.92–6.76) among patients with non-alcoholic steatohepatitis respectively. The respective ORs for CG and GG compared to the CC genotype were 2.35 (0.90–6.13) and 5.05 (1.47–17.29) when comparing non-alcoholic hepatocellular carcinoma to NAFL patients. Among the NAFLD patients, the ORs for G allele frequency when comparing steatosis grade 2–3 to grade 0–1 NAFL, when comparing the NAFLD activity score of ≥ 4 to score ≤ 3, when comparing NASH to NAFLD, when comparing the presence of lobular inflammation to absence, and when comparing the presence of hepatocyte ballooning to absence were 2.33 (1.43–3.80), 1.80 (1.36–2.37), 1.66 (1.42–1.94), 1.58 (1.19–2.10), and 2.63 (1.87–3.69) respectively. Subgroup analysis based on ethnicity showed similar results. Conclusions: PNPLA3 polymorphisms have strong association with the risk for and severity of NAFLDs. PNPLA3 polymorphism plays an evolving role in diagnosis and treatment decisions in patients with NAFLD. PMID:27777887

  8. Nursing Activities Score and Acute Kidney Injury.

    PubMed

    Coelho, Filipe Utuari de Andrade; Watanabe, Mirian; Fonseca, Cassiane Dezoti da; Padilha, Katia Grillo; Vattimo, Maria de Fátima Fernandes

    2017-01-01

    to evaluate the nursing workload in intensive care patients with acute kidney injury (AKI). A quantitative study, conducted in an intensive care unit, from April to August of 2015. The Nursing Activities Score (NAS) and Kidney Disease Improving Global Outcomes (KDIGO) were used to measure nursing workload and to classify the stage of AKI, respectively. A total of 190 patients were included. Patients who developed AKI (44.2%) had higher NAS when compared to those without AKI (43.7% vs 40.7%), p <0.001. Patients with stage 1, 2 and 3 AKI showed higher NAS than those without AKI. A relationship was identified between stage 2 and 3 with those without AKI (p = 0.002 and p <0.001). The NAS was associated with the presence of AKI, the score increased with the progression of the stages, and it was associated with AKI, stage 2 and 3. avaliar a carga de trabalho de enfermagem em pacientes de terapia intensiva com lesão renal aguda (LRA). estudo quantitativo, em Unidade de Terapia Intensiva, no período de abril a agosto de 2015. O Nursing Activities Score (NAS) e o Kidney Disease Improving Global Outcomes (KDIGO) foram utilizados para medir a carga de trabalho de enfermagem e classificar o estágio da LRA, respectivamente. foram incluídos 190 pacientes. Os pacientes que desenvolveram LRA (44,2%) possuíam NAS superiores quando comparados aos sem LRA (43,7% vs 40,7%), p<0,001. Os pacientes com LRA nos estágios 1, 2 e 3 de LRA demonstraram NAS superiores aos sem LRA, houve relação entre os estágios 2 e 3 com os sem LRA, p=0,002 e p<0,001. o NAS apresentou associação com a existência de LRA, visto que seu valor aumenta com a progressão dos estágios, tendo associação com os estágios 2 e 3 de LRA.

  9. Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis.

    PubMed

    Kim, Ji Yeon; Park, Keon Jae; Hwang, Joo-Yeon; Kim, Gyu Hee; Lee, DaeYeon; Lee, Yoo Jeong; Song, Eun Hyun; Yoo, Min-Gyu; Kim, Bong-Jo; Suh, Young Ho; Roh, Gu Seob; Gao, Bin; Kim, Won; Kim, Won-Ho

    2017-08-01

    Non-alcoholic fatty liver disease (NAFLD) contributes to impaired glucose tolerance, leading to type 2 diabetes (T2D); however, the precise mechanisms and target molecules that are involved remain unclear. Activating transcription factor 3 (ATF3) is associated with β-cell dysfunction that is induced by severe stress signals in T2D. We aimed to explore the exact functional role of ATF3 as a mechanistic link between hepatic steatosis and T2D development. Zucker diabetic fatty (ZDF) rats were utilized for animal experiments. An in vivo-jetPEI siRNA delivery system against ATF3 was used for loss-of-function experiments. We analyzed the baseline cross-sectional data derived from the biopsy-proven NAFLD registry (n=322). Human sera and liver tissues were obtained from 43 patients with biopsy-proven NAFLD and from seven healthy participants. ATF3 was highly expressed in the livers of ZDF rats and in human participants with NAFLD and/or T2D. Insulin resistance and hepatic steatosis were associated with increased ATF3 expression and decreased fatty acid oxidation via mitochondrial dysfunction and were attenuated by in vivo ATF3 silencing. Knockdown of ATF3 also ameliorated glucose intolerance, impaired insulin action, and inflammatory responses in ZDF rats. In patients with NAFLD and/or T2D, a significant positive correlation was observed between hepatic ATF3 expression and surrogate markers of T2D, mitochondrial dysfunction, and macrophage infiltration. Increased hepatic ATF3 expression is closely associated with hepatic steatosis and incident T2D; therefore, ATF3 may serve as a potential therapeutic target for NAFLD and hepatic steatosis-induced T2D. Hepatic activating transcription factor 3 (ATF3) may play an important role in oxidative stress-mediated hepatic steatosis and the development of type 2 diabetes (T2D) in a Zucker diabetic fatty (ZDF) rat model and in human patients with non-alcoholic fatty liver disease (NAFLD). Therefore, ATF3 may be a useful biomarker for

  10. Serum folic acid levels are associated with the presence and severity of liver steatosis in Chinese adults.

    PubMed

    Xia, Ming-Feng; Bian, Hua; Zhu, Xiao-Peng; Yan, Hong-Mei; Chang, Xin-Xia; Zhang, Lin-Shan; Lin, Huan-Dong; Hu, Xi-Qi; Gao, Xin

    2017-06-28

    Non-alcoholic fatty liver disease (NAFLD) is a common and strong risk factor for cardiovascular disease and hepatocellular carcinoma. The rapid acceleration of the increase in NAFLD prevalence has exceeded the trends observed for obesity, and has been driven by multiple factors. The aim of this study was to investigate the correlation between the serum levels of folic acid, the endogenous source of methyl groups for DNA methylation, and NAFLD in Chinese adults. The correlations between the serum folic acid levels and NAFLD were investigated in two independent cohorts of 70 subjects who underwent a liver biopsy and 130 subjects with varying liver fat contents, as measured using proton magnetic resonance spectroscopy ( 1 H-MRS). Independent correlations between serum folic acid levels and liver steatosis grades were detected using a multivariate ordinal regression analysis. The diagnostic performances of serum folic acid levels alone and in combination with existing NAFLD prediction scores were compared with those of traditional NAFLD prediction parameters using receiver operating characteristic (ROC) curve analyses. Serum folic acid concentrations were inversely correlated with liver histological steatosis grades (ρ = -0.371, P < 0.001) and the 1 H-MRS-measured liver fat content (r = -0.199, P = 0.038). According to the multivariate ordinal regression analysis, serum folic acid levels were inversely correlated with liver steatosis grades (OR 0.739 [0.594-0.918], P = 0.006) independent of age, gender, BMI, components of metabolic syndrome and the serum TC, LDL-c and HOMA-IR levels. The AUROC of serum folic acid for the diagnosis of NAFLD was 0.75 (0.65-0.83), and the addition of serum folic acid to NAFLD prediction scores significantly improved the diagnostic prediction of NAFLD (AUROC = 0.88 [0.81-0.94]). Low serum folic acid levels were identified as an independent risk factor for NAFLD in the Chinese population. The addition of the serum folic acid

  11. Activation of the GP130-STAT3 axis and its potential implications in nonalcoholic fatty liver disease

    PubMed Central

    Min, Hae-Ki; Mirshahi, Faridoddin; Verdianelli, Aurora; Pacana, Tommy; Patel, Vaishali; Park, Chun-Geon; Choi, Aejin; Lee, Jeong-Hoon; Park, Chung-Berm; Ren, Shunlin

    2015-01-01

    The status of the GP130-STAT3 signaling pathway in humans with nonalcoholic fatty liver disease (NAFLD) and its relevance to disease pathogenesis are unknown. The expression of the gp130-STAT3 axis and gp130 cytokine receptors were studied in subjects with varying phenotypes of NAFLD including nonalcoholic steatohepatitis (NASH) and compared with lean and weight-matched controls without NAFLD. Gp130 and its downstream signaling element (Tyk2 and STAT3) expression were inhibited in obese controls whereas they were increased in NAFLD. IL-6 levels were increased in NASH and correlated with gp130 expression (P < 0.01). Palmitate inhibited gp130-STAT3 expression and signaling. IL-6 and palmitate inhibited hepatic insulin signaling via STAT3-dependent and independent mechanisms, respectively. STAT3 overexpression reversed palmitate-induced lipotoxicity by increasing autophagy (ATG7) and decreasing endoplasmic reticulum stress. These data demonstrate that the STAT3 pathway is activated in NAFLD and can worsen insulin resistance while protecting against other lipotoxic mechanisms of disease pathogenesis. PMID:25747354

  12. Match score affects activity profile and skill performance in professional Australian Football players.

    PubMed

    Sullivan, Courtney; Bilsborough, Johann C; Cianciosi, Michael; Hocking, Joel; Cordy, Justin; Coutts, Aaron J

    2014-05-01

    To examine the influence of quarter outcome and the margin of the score differential on both the physical activity profile and skill performance of players during professional Australian Football matches. Prospective, longitudinal. Physical activity profiles were assessed via microtechnology (Global Positioning System and accelerometer) from 40 professional AF players from the same team during 15 Australian Football League games. Skill performance measures (involvement and effectiveness) and player rank scores (Champion Data(©) Rank) were provided by a commercial statistical provider. The physical performance variables, skill involvements and individual player performance scores were expressed relative to playing time for each quarter. The influence of the quarter result (i.e. win vs. loss) and score margin (i.e. small: <9 points, moderate: 10-18 points, and large: >19 points) on activity profile and skill involvements and skill efficiency performance of players were examined. Skill involvements (total disposals/min, long kicks/min, marks/min, running bounces/min and player rank/min) were greater in quarters won (all p<0.01). In contrast, the players high speed running distance per minute (>14.5 km h(-1), HSR/min), sprints/min and peak speed were higher in losing quarters (all p<0.01). Smaller score margins were associated with increased physical activity (m/min, HSR/min, and body load/min, all p<0.05) and decreased skill efficiency (handball clangers/min and player rank/min, all p<0.05). Professional AF players are likely to have an increased physical activity profile and decreased skill involvement and proficiency when their team is less successful. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  13. A Khorasan Wheat-Based Replacement Diet Improves Risk Profile of Patients With Nonalcoholic Fatty Liver Disease (NAFLD): A Randomized Clinical Trial.

    PubMed

    Dinu, Monica; Whittaker, Anne; Pagliai, Giuditta; Giangrandi, Ilaria; Colombini, Barbara; Gori, Anna Maria; Fiorillo, Claudia; Becatti, Matteo; Casini, Alessandro; Benedettelli, Stefano; Sofi, Francesco

    2018-04-13

    KAMUT khorasan is an ancient grain with widely acclaimed health benefits. The aim of this study was to investigate the effects of a replacement diet with ancient khorasan wheat products in patients with NAFLD, in comparison to a similar replacement diet with control products made from organic semi-whole-grain modern wheat. Forty NAFLD patients (12 M/28 F; age 55.2 ± 10.4 years) with mild to moderate liver steatosis were included. The experimental design was a randomized, double-blind, parallel-arm study with 20 participants assigned to consume either KAMUT khorasan or control wheat products (pasta, bread, crackers, biscuits) over a 3-month period. Anthropometric measurements, blood analyses, and ultrasonography examination were performed at both the beginning and end of each dietary intervention. After the implementation of a general linear model for repeated measurements adjusted for baseline demographic details, risk factors, and medication, alanine aminotransferase (ALT) was significantly reduced by 12%, aspartate aminotransferase (AST) by 14%, alkaline phosphatase (ALP) by 8%, and cholesterol by 6% only in the khorasan group (p < 0.05 for all). Similarly, significant reductions in circulating proinflammatory tumor necrosis factor-alpha by 50%, interleukin l-receptor antagonist-alpha by 37%, interleukin-8 by 24%, and interferon gamma by 24% were evident only in participants who consumed the khorasan products (p < 0.05 for all). Finally, significant improvements in the liver steatosis grading, Doppler perfusion index values, and reactive oxygen species (ROS) production were evident after consumption of both the khorasan and control products. This study suggests that a short-term replacement diet with ancient KAMUT khorasan products is most effective in reducing metabolic risk factors and ameliorating the liver profile in patients with NAFLD.

  14. Relationship between Controlled Attenuation Parameter and Hepatic Steatosis as Assessed by Ultrasound in Alcoholic or Nonalcoholic Fatty Liver Disease.

    PubMed

    Ahn, Jem Ma; Paik, Yong-Han; Min, Sin Yeong; Cho, Ju Yeon; Sohn, Won; Sinn, Dong Hyun; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

    2016-03-01

    The aim of this study was to evaluate the relationship between controlled attenuation parameter (CAP) and hepatic steatosis, as assessed by ultrasound (US) in patients with alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). Patients with either ALD or NAFLD who were diagnosed with fatty liver with US and whose CAP scores were measured, were retrospectively enrolled in this study. The degree of hepatic steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3). A total of 186 patients were included 106 with NAFLD and 80 with ALD. Regarding hepatic steatosis, the CAP score was significantly correlated with US (ρ=0.580, p<0.001), and there was no significant difference between the NAFLD and ALD groups (ρ=0.569, p<0.001; ρ=0.519, p<0.001; p=0.635). Using CAP, area under receiver operating characteristic curves for ≥ S2 and ≥ S3 steatosis were excellent (0.789 and 0.843, respectively). For sensitivity ≥ 90%, CAP cutoffs for the detection of ≥ S2 and ≥ S3 steastosis were separated with a gap of approximately 35 dB/m in all patients and in each of the NAFLD and ALD groups. The CAP score is well correlated with hepatic steatosis, as assessed by US, in both ALD and NAFLD.

  15. Peroxisome proliferator-activated receptors as targets to treat non-alcoholic fatty liver disease

    PubMed Central

    Souza-Mello, Vanessa

    2015-01-01

    Lately, the world has faced tremendous progress in the understanding of non-alcoholic fatty liver disease (NAFLD) pathogenesis due to rising obesity rates. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that modulate the expression of genes involved in lipid metabolism, energy homeostasis and inflammation, being altered in diet-induced obesity. Experimental evidences show that PPAR-alpha is the master regulator of hepatic beta-oxidation (mitochondrial and peroxisomal) and microsomal omega-oxidation, being markedly decreased by high-fat (HF) intake. PPAR-beta/delta is crucial to the regulation of forkhead box-containing protein O subfamily-1 expression and, hence, the modulation of enzymes that trigger hepatic gluconeogenesis. In addition, PPAR-beta/delta can activate hepatic stellate cells aiming to the hepatic recovery from chronic insult. On the contrary, PPAR-gamma upregulation by HF diets maximizes NAFLD through the induction of lipogenic factors, which are implicated in the fatty acid synthesis. Excessive dietary sugars also upregulate PPAR-gamma, triggering de novo lipogenesis and the consequent lipid droplets deposition within hepatocytes. Targeting PPARs to treat NAFLD seems a fruitful approach as PPAR-alpha agonist elicits expressive decrease in hepatic steatosis by increasing mitochondrial beta-oxidation, besides reduced lipogenesis. PPAR-beta/delta ameliorates hepatic insulin resistance by decreasing hepatic gluconeogenesis at postprandial stage. Total PPAR-gamma activation can exert noxious effects by stimulating hepatic lipogenesis. However, partial PPAR-gamma activation leads to benefits, mainly mediated by increased adiponectin expression and decreased insulin resistance. Further studies are necessary aiming at translational approaches useful to treat NAFLD in humans worldwide by targeting PPARs. PMID:26052390

  16. Arctigenin protects against steatosis in WRL68 hepatocytes through activation of phosphoinositide 3-kinase/protein kinase B and AMP-activated protein kinase pathways.

    PubMed

    Chen, Kung-Yen; Lin, Jui-An; Yao, Han-Yun; Hsu, An-Chih; Tai, Yu-Ting; Chen, Jui-Tai; Hsieh, Mao-Chih; Shen, Tang-Long; Hsu, Ren-Yi; Wu, Hong-Tan; Wang, Guey Horng; Ho, Bing-Ying; Chen, Yu-Pei

    2018-04-01

    Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation-associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays. Quantitative RT-PCR analysis demonstrated that ATG significantly mitigated the expression of acetylcoenzyme A carboxylase 1 and sterol regulatory element-binding protein-1 and significantly increased the expression of carnitine palmitoyltransferase 1 and peroxisome proliferator-activated receptor alpha. The 40 targets of the Human Inflammation Antibody Array indicated that ATG significantly inhibited the elevation of the U937 lymphocyte chemoattractant, ICAM-1, IL-1β, IL-6, IL-6sR, IL-7, and IL-8. ATG could activate the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK) pathways and could increase the phosphorylation levels of Akt and AMPK to mediate cell survival, lipid metabolism, oxidation stress, and inflammation. Thus, we demonstrated that ATG could inhibit NAFLD progression associated with lipid oxidation-associated lipotoxicity and inflammation, and we provided insights into the underlying mechanisms and revealed potential targets to enable a thorough understanding of NAFLD progression. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. PNPLA3 genotype increases susceptibility of nonalcoholic steatohepatitis among obese patients with nonalcoholic fatty liver disease.

    PubMed

    Tai, Chi-Ming; Huang, Chih-Kun; Tu, Hung-Pin; Hwang, Jau-Chung; Chang, Chi-Yang; Yu, Ming-Lung

    2015-01-01

    The patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 variant is associated with histologic disease severity in patients with nonalcoholic fatty liver disease (NAFLD); however, whether the PNPLA3 genotype has an effect on susceptibility of nonalcoholic steatohepatitis (NASH) from NAFLD among severely obese patients remains unclear. The objective of this study was to investigate the role of the PNPLA3 genotype on NASH in severely obese Asian patients with NAFLD. The PNPLA3 rs738409 genotype was determined in 181 severely obese patients who underwent bariatric surgery. The diagnosis of NASH and the NAFLD activity score (NAS) were determined by liver histopathology. Of the 181 patients, 29 (16.0%), 60 (33.2%), and 92 (50.8%) were in the non-NAFLD, steatosis, and NASH groups, respectively. The PNPLA3 rs738409 GG genotype was associated with higher liver enzymes and a higher risk for NASH (odds ratio [OR], 3.72; 95% CI, 1.25-11.05). The GG genotype was also associated with histologic severity of NAFLD, including higher steatosis grade (OR, 9.94; 95% CI, 2.20-44.83 for patients with grade 3 steatosis) and NAS (OR, 11.49; 95% CI, 2.50-52.83 for patients with a NAS ≥5). Finally, multiple logistic regression also showed that the GG genotype was an independent risk factor for NASH (OR, 3.58; 95% CI, 1.15-11.12) in NAFLD patients. The PNPLA3 rs738409 GG genotype increases susceptibility of NASH in severely obese Asians with NAFLD and correlates to histologic severity of NAFLD. Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  18. Relationships between spatial activities and scores on the mental rotation test as a function of sex.

    PubMed

    Ginn, Sheryl R; Pickens, Stefanie J

    2005-06-01

    Previous results suggested that female college students' scores on the Mental Rotations Test might be related to their prior experience with spatial tasks. For example, women who played video games scored better on the test than their non-game-playing peers, whereas playing video games was not related to men's scores. The present study examined whether participation in different types of spatial activities would be related to women's performance on the Mental Rotations Test. 31 men and 59 women enrolled at a small, private church-affiliated university and majoring in art or music as well as students who participated in intercollegiate athletics completed the Mental Rotations Test. Women's scores on the Mental Rotations Test benefitted from experience with spatial activities; the more types of experience the women had, the better their scores. Thus women who were athletes, musicians, or artists scored better than those women who had no experience with these activities. The opposite results were found for the men. Efforts are currently underway to assess how length of experience and which types of experience are related to scores.

  19. SARM1 deletion restrains NAFLD induced by high fat diet (HFD) through reducing inflammation, oxidative stress and lipid accumulation.

    PubMed

    Pan, Zhen-Guo; An, Xu-Sheng

    2018-04-06

    SARM1 (Sterile alpha and armadillo motif-containing protein 1) is the recently identified TIR domain-containing cytosolic protein, which is involved in toll-like receptors (TLRs) signaling transduction. In the present study, the role of SARM1 in high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) progression was explored. We found that SARM1 was expressed highly in fatty liver. And SARM1-knockout (KO) reduced steatohepatitis and metabolic disorders induced by HFD. SARM1-deletion decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in HFD-fed mice. Additionally, inflammatory response caused by HFD was alleviated by SARM1-deletion through inactivating TLR4/7/9 and nuclear factor kappa B (NF-κB) pathways. Of note, SARM1-deletion also reduced the expressions of inflammation-associated molecules in hypothalamus of HFD-fed mice. Furthermore, HFD administration led to oxidative stress in liver of mice, while being decreased in SARM1-KO mice. Moreover, SARM1-ablation improved lipid dyslipidemia by suppressing the mRNA levels of genes, linked to glycolysis, lipogenesis and transcriptional regulation. Insulin resistance was also attenuated by SARM1-deficiency through enhancing the activation of liver Akt/glycogen synthase kinase-3β (GSK3β) and insulin receptor substrate-1 (IRS1)/FOXO1 pathways in HFD-fed mice. Also, SARM1-knockout improved neuropeptide Y (NPY), Pro-Opiomelanocortins (POMC), Agouti-related Protein (AGRP) and Cocaine-and-Amphetamine Responsive Transcript 1 (CART1) expressions in hypothalamus of mice after HFD administration. In vitro, we found that the reduction of inflammatory response, oxidative stress and dyslipidemia induced by SARM1-knockout in primary hepatocytes after fructose stimulation was largely attributed to its suppression to TLR4/7/9. Together, the findings demonstrated that SARM1 might be an effective target for developing effective therapeutic strategies against NAFLD. Copyright © 2018

  20. Role of docosahexaenoic acid treatment in improving liver histology in pediatric nonalcoholic fatty liver disease.

    PubMed

    Nobili, Valerio; Carpino, Guido; Alisi, Anna; De Vito, Rita; Franchitto, Antonio; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of liver-related morbidity and mortality in children. Recently, we have reported the effects of docosahexaenoic acid (DHA), the major dietary long-chain polyunsaturated fatty acids, in children with NAFLD. DHA exerts a potent anti-inflammatory activity through the G protein-coupled receptor (GPR)120. Our aim was to investigate in pediatric NAFLD the mechanisms underlying the effects of DHA administration on histo-pathological aspects, GPR120 expression, hepatic progenitor cell activation and macrophage pool. 20 children with untreated NAFLD were included. Children were treated with DHA for 18 months. Liver biopsies before and after the treatment were analyzed. Hepatic progenitor cell activation, macrophage pool and GPR120 expression were evaluated and correlated with clinical and histo-pathological parameters. GPR120 was expressed by hepatocytes, liver macrophages, and hepatic progenitor cells. After DHA treatment, the following modifications were present: i) the improvement of histo-pathological parameters such as NAFLD activity score, ballooning, and steatosis; ii) the reduction of hepatic progenitor cell activation in correlation with histo-pathological parameters; iii) the reduction of the number of inflammatory macrophages; iv) the increase of GPR120 expression in hepatocytes; v) the reduction of serine-311-phosphorylated nuclear factor kappa B (NF-κB) nuclear translocation in hepatocytes and macrophages in correlation with serum inflammatory cytokines. DHA could modulate hepatic progenitor cell activation, hepatocyte survival and macrophage polarization through the interaction with GPR120 and NF-κB repression. In this scenario, the modulation of GPR120 exploits a novel crucial role in the regulation of the cell-to-cell cross-talk that drives inflammatory response, hepatic progenitor cell activation and hepatocyte survival.

  1. Novel Semiquantitative Bone Marrow Oedema Score and Fracture Score for the Magnetic Resonance Imaging Assessment of the Active Charcot Foot in Diabetes

    PubMed Central

    Meacock, L.; Donaldson, Ana; Isaac, A.; Briody, A.; Ramnarine, R.; Edmonds, M. E.; Elias, D. A.

    2017-01-01

    There are no accepted methods to grade bone marrow oedema (BMO) and fracture on magnetic resonance imaging (MRI) scans in Charcot osteoarthropathy. The aim was to devise semiquantitative BMO and fracture scores on foot and ankle MRI scans in diabetic patients with active osteoarthropathy and to assess the agreement in using these scores. Three radiologists assessed 45 scans (Siemens Avanto 1.5T, dedicated foot and ankle coil) and scored independently twenty-two bones (proximal phalanges, medial and lateral sesamoids, metatarsals, tarsals, distal tibial plafond, and medial and lateral malleoli) for BMO (0—no oedema, 1—oedema < 50% of bone volume, and 2—oedema > 50% of bone volume) and fracture (0—no fracture, 1—fracture, and 2—collapse/fragmentation). Interobserver agreement and intraobserver agreement were measured using multilevel modelling and intraclass correlation (ICC). The interobserver agreement for the total BMO and fracture scores was very good (ICC = 0.83, 95% confidence intervals (CI) 0.76, 0.91) and good (ICC = 0.62; 95% CI 0.48, 0.76), respectively. The intraobserver agreement for the total BMO and fracture scores was good (ICC = 0.78, 95% CI 0.6, 0.95) and fair to moderate (ICC = 0.44; 95% CI 0.14, 0.74), respectively. The proposed BMO and fracture scores are reliable and can be used to grade the extent of bone damage in the active Charcot foot. PMID:29230422

  2. SCORE/ACE Counselor Handbook. Service Corps of Retired Executives. Active Corps of Executives.

    ERIC Educational Resources Information Center

    Landsverk, Arvel; And Others

    This counselor handbook is intended to help Service Corps of Retired Executives/Active Corps of Executives (SCORE/ACE) counselors to plan and conduct counseling services more effectively. Included in the introductory section are an overview of the SCORE/ACE counseling program, a discussion of what the counselor does, directions for completing…

  3. Underappreciation of non-alcoholic fatty liver disease by primary care clinicians: limited awareness of surrogate markers of fibrosis.

    PubMed

    Patel, Preya J; Banh, Xuan; Horsfall, Leigh U; Hayward, Kelly L; Hossain, Fabrina; Johnson, Tracey; Stuart, Katherine A; Brown, Nigel N; Saad, Nivene; Clouston, Andrew; Irvine, Katharine M; Russell, Anthony W; Valery, Patricia C; Williams, Suzanne; Powell, Elizabeth E

    2018-02-01

    Non-alcoholic fatty liver disease (NAFLD) is a common cause of incidental liver test abnormalities. General practitioners (GP) have a key role in identifying people with NAFLD at risk of significant liver disease. Recent specialist guidelines emphasise the use of fibrosis algorithms or serum biomarkers rather than routine liver tests, to assess advanced fibrosis. To evaluate primary care clinicians' current approach to diagnosis, management and referral of NAFLD. A cross-sectional survey of primary care clinicians was undertaken through a structured questionnaire about NAFLD. A convenience sample of general practice clinics and general practice conferences in Metropolitan Brisbane and regional south east Queensland was selected. A total of 108 primary care clinicians completed the survey (participation rate 100%). Fifty-one percent of respondents considered the prevalence of NAFLD in the general population to be ≤10%. Twenty-four percent of respondents felt that liver enzymes were sufficiently sensitive to detect underlying NAFLD. Most respondents were unsure whether the Fibrosis 4 score (62.7% unsure) or Enhanced Liver Fibrosis score (63.7% unsure) could help to identify advanced fibrosis or cirrhosis. Although 47% of respondents said they would refer a patient to a Gastroenterologist/Hepatologist if they suspect the patient has NAFLD, 44.1% do not make any referrals. Of concern, 70.6% of clinicians said they were unlikely to refer a patient to Hepatology unless liver function tests are abnormal. Our findings demonstrate that many primary care clinicians underestimate the prevalence of NAFLD and under-recognise the clinical spectrum of NAFLD and how this is assessed. © 2017 Royal Australasian College of Physicians.

  4. Are students' impressions of improved learning through active learning methods reflected by improved test scores?

    PubMed

    Everly, Marcee C

    2013-02-01

    To report the transformation from lecture to more active learning methods in a maternity nursing course and to evaluate whether student perception of improved learning through active-learning methods is supported by improved test scores. The process of transforming a course into an active-learning model of teaching is described. A voluntary mid-semester survey for student acceptance of the new teaching method was conducted. Course examination results, from both a standardized exam and a cumulative final exam, among students who received lecture in the classroom and students who had active learning activities in the classroom were compared. Active learning activities were very acceptable to students. The majority of students reported learning more from having active-learning activities in the classroom rather than lecture-only and this belief was supported by improved test scores. Students who had active learning activities in the classroom scored significantly higher on a standardized assessment test than students who received lecture only. The findings support the use of student reflection to evaluate the effectiveness of active-learning methods and help validate the use of student reflection of improved learning in other research projects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Low physical activity and energy dense Malaysian foods are associated with non-alcoholic fatty liver disease in centrally obese but not in non-centrally obese patients with diabetes mellitus.

    PubMed

    Chan, Wah-Kheong; Tan, Alexander Tong-Boon; Vethakkan, Shireene Ratna; Tah, Pei-Chien; Vijayananthan, Anushya; Goh, Khean-Lee

    2015-01-01

    To study the dietary intake and level of physical activity (PA) of patients with diabetes mellitus and the association with non-alcoholic fatty liver disease (NAFLD). Consecutive adult patients with type 2 diabetes mellitus seen in our hospital diabetes clinic were enrolled. The Global Physical Activity Questionnaire and a semi-quantitative food-frequency questionnaire were used to assess PA and dietary intake, respectively. Diagnosis of NAFLD was ultrasound-based and following exclusion of significant alcohol intake and other causes of chronic liver disease. Data for 299 patients were analyzed (mean age 63.3±10.5 years old, 41.1% male). Prevalence of NAFLD was 49.2%. Patients with low PA were more likely to have NAFLD (OR=1.75, 95% CI=1.03-2.99, p=0.029). There was no significant difference in energy intake, intake of macronutrients and percentage energy intake from each macronutrient, high sugar food, high cholesterol food and high SFA food between patients with and without NAFLD. Among centrally obese patients, patients with low PA and in the highest quartile of percentage energy intake from fat (OR=4.03, 95% CI=1.12-15.0, p=0.015), high cholesterol food (OR=3.61, 95% CI=1.37-9.72, p=0.004) and high SFA food (OR=2.67, 95% CI=1.08-6.67, p=0.019) were most likely to have NAFLD. Among those who were not centrally obese, PA and percentage energy intake from fat, high cholesterol food and high SFA food was not associated with NAFLD. Low PA and high percentage energy intake from fat, high cholesterol food and high SFA food is associated with NAFLD in centrally obese but not in non-centrally obese patients with diabetes mellitus.

  6. Waist circumference as a marker for screening nonalcoholic fatty liver disease in obese adolescents

    PubMed Central

    Clemente, Ana Paula Grotti; Dal Molin, Bárbara; de Carvalho-Ferreira, Joana Pereira; Campos, Raquel Munhoz da Silveira; Ganen, Aline de Piano; Tock, Lian; de Mello, Marco Túlio; Dâmaso, Ana Raimunda

    2016-01-01

    Abstract Objective: To assess the relationship between the degree of waist circumference (WC) and nonalcoholic fatty liver disease (NAFLD) in obese adolescents of both genders, analyzed according to quartiles of WC. Methods: Cross-sectional study that involved 247 obese adolescents aged 12–19 years. Mean values of the nutritional parameters and serum analyses were compared with the groups using the independent t-test. Pearson correlation coefficient was used to determine the relationship of the parameters studied. Chi-square test for trend was used to determine the relationship between the prevalence of the NAFLD and WC quartile by gender. Results: NAFLD were presented in 60% of the study participants. Obese adolescents in the 3rd and 4th quartiles of WC presented higher prevalence of NAFLD when compared with that in the 1st quartile in both genders. The NAFLD patients had significantly higher values for body weight, BMI (body mass index), BAZ-score (BMI-for-age z-scores), total fat (% and kg), WC, visceral fat, insulin, insulin resistance index (HOMA-IR), aspartate aminotransferase and alanine aminotransferase, when compared with non-NAFLD obese adolescents. Conclusions: In conclusion, the results presented here suggest that an increase in WC can reliably predict the risk of NAFLD in obese adolescents. This is a low cost and easy-to-use tool that can help in screening in adolescents. PMID:26830602

  7. The impact of non-alcoholic fatty liver disease fibrosis score on cardiac prognosis in patients with chronic heart failure.

    PubMed

    Takahashi, Tetsuya; Watanabe, Tetsu; Shishido, Tetsuro; Watanabe, Ken; Sugai, Takayuki; Toshima, Taku; Kinoshita, Daisuke; Yokoyama, Miyuki; Tamura, Harutoshi; Nishiyama, Satoshi; Arimoto, Takanori; Takahashi, Hiroki; Yamanaka, Tamon; Miyamoto, Takuya; Kubota, Isao

    2018-07-01

    Liver abnormalities have a strong impact on clinical outcomes in patients with heart failure (HF), and are known as cardio-hepatic syndrome. The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been developed to identify liver fibrosis in patients with NAFLD. It remains to be determined whether NFS is associated with cardiovascular prognosis in patients with chronic heart failure (CHF). We calculated NFS in 516 patients with CHF admitted to our hospital. The clinical endpoints were deaths due to progressive HF, myocardial infarction, stroke, and sudden cardiac death, and rehospitalization for worsening HF. There were 173 cardiovascular events noted during a median follow-up of 464 days. Patients with cardiovascular events showed a higher NFS as compared with those without. We divided the patients into four groups according to quartiles of NFS. The proportion of New York Heart Association functional class III/IV and serum brain natriuretic peptide levels were increased with increasing NFS. Kaplan-Meier analysis revealed that cardiovascular event rate was increased with increasing NFS in patients with CHF. In multivariate Cox proportional hazards analysis, NFS was independently associated with cardiovascular events after adjustment for confounding factors. Elevated NFS was associated with unfavorable outcomes in patients with CHF. Liver fibrosis assessed by NFS may provide valuable prognostic information in patients with CHF.

  8. Circulating dipeptidyl peptidase-4 activity correlates with measures of hepatocyte apoptosis and fibrosis in non-alcoholic fatty liver disease in type 2 diabetes mellitus and obesity: A dual cohort cross-sectional study.

    PubMed

    Williams, Kathryn H; Vieira De Ribeiro, Ana Júlia; Prakoso, Emilia; Veillard, Anne-Sophie; Shackel, Nicholas A; Brooks, Belinda; Bu, Yangmin; Cavanagh, Erika; Raleigh, Jim; McLennan, Susan V; McCaughan, Geoffrey W; Keane, Fiona M; Zekry, Amany; Gorrell, Mark D; Twigg, Stephen M

    2015-11-01

    Intrahepatic expression of dipeptidyl peptidase-4 (DPP4), and circulating DPP4 (cDPP4) levels and its enzymatic activity, are increased in non-alcoholic fatty liver disease (NAFLD) and in type 2 diabetes mellitus and/or obesity. DPP4 has been implicated as a causative factor in NAFLD progression but few studies have examined associations between cDPP4 activity and NAFLD severity in humans. This study aimed to examine the relationship of cDPP4 activity with measures of liver disease severity in NAFLD in subjects with diabetes and/or obesity. cDPP4 was measured in 106 individuals with type 2 diabetes who had transient elastography (Cohort 1) and 145 individuals with morbid obesity who had liver biopsy (Cohort 2). Both cohorts had caspase-cleaved keratin-18 (ccK18) measured as a marker of apoptosis. Natural log increases in cDPP4 activity were associated with increasing quartiles of ccK18 (Cohorts 1 and 2) and with median liver stiffness ≥10.3 kPa (Cohort 1) and significant fibrosis (F ≥ 2) on liver biopsy (Cohort 2). In diabetes and/or obesity, cDPP4 activity is associated with current apoptosis and liver fibrosis. Given the pathogenic mechanisms by which DPP4 may progress NAFLD, measurement of cDPP4 activity may have utility to predict disease progression and DPP4 inhibition may improve liver histology over time. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  9. A preliminary score for the assessment of disease activity in hereditary recurrent fevers: results from the AIDAI (Auto-Inflammatory Diseases Activity Index) Consensus Conference

    PubMed Central

    Piram, Maryam; Frenkel, Joost; Gattorno, Marco; Ozen, Seza; Lachmann, Helen J; Goldbach-Mansky, Raphaela; Hentgen, Véronique; Neven, Bénédicte; Stankovic Stojanovic, Katia; Simon, Anna; Kuemmerle-Deschner, Jasmin; Hoffman, Hal; Stojanov, Silvia; Duquesne, Agnès; Pillet, Pascal; Martini, Alberto; Pouchot, Jacques; Koné-Paut, Isabelle

    2012-01-01

    Background The systemic autoinflammatory disorders (SAID) share many clinical manifestations, albeit with variable patterns, intensity and frequency. A common definition of disease activity would be rational and useful in the management of these lifelong diseases. Moreover, standardised disease activity scores are required for the assessment of new therapies in constant development. The aim of this study was to develop preliminary activity scores for familial Mediterranean fever, mevalonate kinase deficiency, tumour necrosis factor receptor-1-associated periodic syndrome and cryopyrin-associated periodic syndromes (CAPS). Methods The study was conducted using two well-recognised consensus formation methods: the Delphi technique and the nominal group technique. The results from a two-step survey and data from parent/patient interviews were used as preliminary data to develop the agenda for a consensus conference to build a provisional scoring system. Results 24 of 65 experts in SAID from 20 countries answered the web questionnaire and 16 attended the consensus conference. There was consensus agreement to develop separate activity scores for each disease but with a common format based on patient diaries. Fever and disease-specific clinical variables were scored according to their severity. A final score was generated by summing the score of all the variables divided by the number of days over which the diary was completed. Scores varied from 0 to 16 (0–13 in CAPS). These scores were developed for the purpose of clinical studies but could be used in clinical practice. Conclusion Using widely recognised consensus formation techniques, preliminary scores were obtained to measure disease activity in four main SAID. Further prospective validation study of this instrument will follow. PMID:21081528

  10. Characterization of European-ancestry NAFLD-Associated Variants in Individuals of African and Hispanic Descent

    PubMed Central

    Palmer, Nicholette D; Musani, Solomon K; Yerges-Armstrong, Laura M; Feitosa, Mary F; Bielak, Lawrence F; Hernaez, Ruben; Kahali, Bratati; Carr, J Jeffrey; Harris, Tamara B; Jhun, Min A; Kardia, Sharon LR; Langefeld, Carl D; Mosley, Thomas H; Norris, Jill M; Smith, Albert V; Taylor, Herman A; Wagenknecht, Lynne E; Liu, Jiankang; Borecki, Ingrid B; Peyser, Patricia A; Speliotes, Elizabeth K

    2013-01-01

    Nonalcoholic Fatty Liver Disease (NAFLD) is an obesity-related condition affecting over 50% of individuals in some populations and is expected to become the number one cause of liver disease worldwide by 2020. Common, robustly associated genetic variants in/near five genes were identified for hepatic steatosis, a quantifiable component of NAFLD, in European-ancestry individuals. Here we tested whether these variants were associated with hepatic steatosis in African and/or Hispanic Americans and fine-mapped the observed association signals. We measured hepatic steatosis using computed tomography in five African-American (n=3124) and one Hispanic-American (n=849) cohorts. All analyses controlled for variation in age, age2, gender, alcoholic drinks, and population substructure. Heritability of hepatic steatosis was estimated in three cohorts. Variants in/near PNPLA3, NCAN, LYPLAL1, GCKR, and PPP1R3B were tested for association with hepatic steatosis using a regression framework in each cohort and meta-analyzed. Fine-mapping across African-American cohorts was conducted using meta-analysis. African- and Hispanic-American cohorts were 33.9/37.5% male, with average age of 58.6/42.6 years and body mass index of 31.8/28.9kg/m2, respectively. Hepatic steatosis was 0.20–0.34 heritable in African-and Hispanic-American families (p<0.02 in each cohort). Variants in or near PNPLA3, NCAN, GCKR, PPP1R3B in African Americans and PNPLA3 and PPP1R3B in Hispanic Americans were significantly associated with hepatic steatosis; however, allele frequency and effect size varied across ancestries. Fine-mapping in African Americans highlighted missense variants at PNPLA3 and GCKR and redefined the association region at LYPLAL1. Conclusions We show for the first time that multiple genetic variants are associated with hepatic steatosis across ancestries and explain a substantial proportion of the genetic predisposition in African and Hispanic Americans. Missense variants in PNPLA3 and GCKR

  11. MiR-149 Compromises the Reactions of Liver Cells to Fatty Acid via its Polymorphism and Increases Non-Alcoholic Fatty Liver Disease (NAFLD) Risk by Targeting Methylene Tetrahydrofolate Reductase (MTHFR).

    PubMed

    An, Xianchao; Yang, Zonglin; An, Zhengzhuang

    2017-05-16

    BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem, and microRNA (miRNA) has been reported to be involved in NAFLD. The objective of our study was to explore the effect of polymorphism in miR-149 on the pathogenesis of NAFLD. MATERIAL AND METHODS Real-time PCR was performed to explore the effect of long-chain fatty acid (FFA) on the level of miR-149 and methylene tetrahydrofolate reductase (MTHFR). Then in-silicon analysis and luciferase assay were investigated to verify MTHFR was the target gene of miR-149. Finally, Western-blot analysis and real-time PCR were performed to confirm the control of MTHFR by miR-149. RESULTS In this study, we found that miR-149 was apparently upregulated in hepatocytes genotyped as TT treated with FFA; and MTHFR in hepatocytes genotyped as TT treated with FFA was evidently downregulated compared to control. Whereas, FFA had no obvious effect on MTHFR level in hepatocytes genotyped as CC. We searched an online miRNA database and found that miR-149 was a regulator of MTHFR expression, which was confirmed by luciferase assay. In hepatocytes genotyped as TT and treated with or without FFA, miR-149 mimic dose-dependently decreased the level of MTHFR, and miR-149 inhibitor dose-dependently increased the level of MTHFR. And in hepatocytes genotyped as CC treated with or without FFA exhibited a similar inhibition effect of miR-149 on expression of MTHFR. CONCLUSIONS The data suggested that the polymorphism in miR-149 played an important role in the development of NAFLD via altering the expression of miR-149 as well as its target, MTHFR.

  12. MiR-149 Compromises the Reactions of Liver Cells to Fatty Acid via its Polymorphism and Increases Non-Alcoholic Fatty Liver Disease (NAFLD) Risk by Targeting Methylene Tetrahydrofolate Reductase (MTHFR)

    PubMed Central

    An, Xianchao; Yang, Zonglin; An, Zhengzhuang

    2017-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem, and microRNA (miRNA) has been reported to be involved in NAFLD. The objective of our study was to explore the effect of polymorphism in miR-149 on the pathogenesis of NAFLD. Material/Methods Real-time PCR was performed to explore the effect of long-chain fatty acid (FFA) on the level of miR-149 and methylene tetrahydrofolate reductase (MTHFR). Then in-silicon analysis and luciferase assay were investigated to verify MTHFR was the target gene of miR-149. Finally, Western-blot analysis and real-time PCR were performed to confirm the control of MTHFR by miR-149. Results In this study, we found that miR-149 was apparently upregulated in hepatocytes genotyped as TT treated with FFA; and MTHFR in hepatocytes genotyped as TT treated with FFA was evidently downregulated compared to control. Whereas, FFA had no obvious effect on MTHFR level in hepatocytes genotyped as CC. We searched an online miRNA database and found that miR-149 was a regulator of MTHFR expression, which was confirmed by luciferase assay. In hepatocytes genotyped as TT and treated with or without FFA, miR-149 mimic dose-dependently decreased the level of MTHFR, and miR-149 inhibitor dose-dependently increased the level of MTHFR. And in hepatocytes genotyped as CC treated with or without FFA exhibited a similar inhibition effect of miR-149 on expression of MTHFR. Conclusions The data suggested that the polymorphism in miR-149 played an important role in the development of NAFLD via altering the expression of miR-149 as well as its target, MTHFR. PMID:28507283

  13. [Validating the Spanish version of the Nursing Activities Score].

    PubMed

    Sánchez-Sánchez, M M; Arias-Rivera, S; Fraile-Gamo, M P; Thuissard-Vasallo, I J; Frutos-Vivar, F

    2015-01-01

    Validating workload scores ensures that they are appropriate for the purpose for which they were developed. To validate the Nursing Activities Score (NAS) Spanish version. Observational and prospective study. 1,045 patients who were admitted to a medical-surgical unit and a serious burns unit in 2006 were included. The nurse in charge assessed patient workloads by Nine Equivalent of Nursing Manpower use Score and NAS. To assess the internal consistency of the measurements of NAS, item-test correlations, Cronbach's α and Cronbach's α corrected by omitting each of the items were calculated. The intraobserver and interobserver reliability were assessed with the intraclass correlation coefficient by viewing recordings and Kappa (interobserver reliability) was estimated. For the analysis of internal validity, a factorial principal components analysis was performed. Convergent validity was assessed using the Spearman correlation coefficient values obtained from the Nine Equivalent of Nursing Manpower use Score and Spanish-NAS scales. For internal consistency, 164 questionnaires were analysed and a Cronbach's α of 0.373 was calculated. The intraclass correlation coefficient for intraobserver reliability estimate was 0.837 (95% IC: 0.466-0.950) and 0.662 (95% IC: 0.033-0.882) for interobserver reliability. The estimated kappa was 0.371. For internal validity, exploratory factor analysis showed that the first item explained 58.9% of the variance of the questionnaire. For convergent validity 1006 questionnaires were included and a Spearman correlation coefficient of 0.746 was observed. The psychometric properties of Spanish-NAS are acceptable. Copyright © 2014 Elsevier España, S.L.U. y SEEIUC. All rights reserved.

  14. Assessment of the Item Selection and Weighting in the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis

    PubMed Central

    MAHR, ALFRED D.; NEOGI, TUHINA; LAVALLEY, MICHAEL P.; DAVIS, JOHN C.; HOFFMAN, GARY S.; MCCUNE, W. JOSEPH; SPECKS, ULRICH; SPIERA, ROBERT F.; ST.CLAIR, E. WILLIAM; STONE, JOHN H.; MERKEL, PETER A.

    2013-01-01

    Objective To assess the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) with respect to its selection and weighting of items. Methods This study used the BVAS/WG data from the Wegener's Granulomatosis Etanercept Trial. The scoring frequencies of the 34 predefined items and any “other” items added by clinicians were calculated. Using linear regression with generalized estimating equations in which the physician global assessment (PGA) of disease activity was the dependent variable, we computed weights for all predefined items. We also created variables for clinical manifestations frequently added as other items, and computed weights for these as well. We searched for the model that included the items and their generated weights yielding an activity score with the highest R2 to predict the PGA. Results We analyzed 2,044 BVAS/WG assessments from 180 patients; 734 assessments were scored during active disease. The highest R2 with the PGA was obtained by scoring WG activity based on the following items: the 25 predefined items rated on ≥5 visits, the 2 newly created fatigue and weight loss variables, the remaining minor other and major other items, and a variable that signified whether new or worse items were present at a specific visit. The weights assigned to the items ranged from 1 to 21. Compared with the original BVAS/WG, this modified score correlated significantly more strongly with the PGA. Conclusion This study suggests possibilities to enhance the item selection and weighting of the BVAS/WG. These changes may increase this instrument's ability to capture the continuum of disease activity in WG. PMID:18512722

  15. Comparing sixteen scoring functions for predicting biological activities of ligands for protein targets.

    PubMed

    Xu, Weijun; Lucke, Andrew J; Fairlie, David P

    2015-04-01

    Accurately predicting relative binding affinities and biological potencies for ligands that interact with proteins remains a significant challenge for computational chemists. Most evaluations of docking and scoring algorithms have focused on enhancing ligand affinity for a protein by optimizing docking poses and enrichment factors during virtual screening. However, there is still relatively limited information on the accuracy of commercially available docking and scoring software programs for correctly predicting binding affinities and biological activities of structurally related inhibitors of different enzyme classes. Presented here is a comparative evaluation of eight molecular docking programs (Autodock Vina, Fitted, FlexX, Fred, Glide, GOLD, LibDock, MolDock) using sixteen docking and scoring functions to predict the rank-order activity of different ligand series for six pharmacologically important protein and enzyme targets (Factor Xa, Cdk2 kinase, Aurora A kinase, COX-2, pla2g2a, β Estrogen receptor). Use of Fitted gave an excellent correlation (Pearson 0.86, Spearman 0.91) between predicted and experimental binding only for Cdk2 kinase inhibitors. FlexX and GOLDScore produced good correlations (Pearson>0.6) for hydrophilic targets such as Factor Xa, Cdk2 kinase and Aurora A kinase. By contrast, pla2g2a and COX-2 emerged as difficult targets for scoring functions to predict ligand activities. Although possessing a high hydrophobicity in its binding site, β Estrogen receptor produced reasonable correlations using LibDock (Pearson 0.75, Spearman 0.68). These findings can assist medicinal chemists to better match scoring functions with ligand-target systems for hit-to-lead optimization using computer-aided drug design approaches. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Convergence Insufficiency Symptom Survey Scores for Reading Versus Other Near Visual Activities in School-Age Children.

    PubMed

    Clark, Tiana Y; Clark, Robert A

    2015-11-01

    To measure the difference in Convergence Insufficiency Symptom Survey scores for reading vs favorite near visual activities. Comparative validity analysis of diagnostic tools. At a single clinical private practice, 100 children aged 9-18 with normal binocular vision were recruited to receive either the original survey emphasizing reading or a modified survey replacing "reading" with their favorite near activity. Average survey scores and subscores for questions emphasizing fatigue, discomfort, impaired vision, and cognitive performance were compared using t tests, while responses to individual questions were compared using Mann-Whitney U tests. The average reading survey score was significantly greater than the favorite near activity survey score (14.1 ± 11.5 vs 6.7 ± 5.8, P = .0001). The largest difference resulted from questions emphasizing cognitive performance (subscore 5.8 ± 4.3 vs 2.0 ± 2.1, P = .0000002), although significant differences were also found for fatigue (5.4 ± 3.8 vs 3.0 ± 2.7, P = .0003), discomfort (3.9 ± 4.6 vs 1.8 ± 2.2, P = .004), and impaired vision (3.2 ± 3.9 vs 1.8 ± 2.2, P = .02). Significant differences were found for 7 survey questions, with higher symptom scores for the reading survey in every case. Using survey scores ≥16 to diagnose convergence insufficiency, significantly more children taking the reading survey would have been diagnosed with convergence insufficiency than children taking the favorite near activity survey (19 of 50 [38%] vs 5 of 50 [10%], P = .001). By emphasizing reading, the Convergence Insufficiency Symptom Survey score significantly overestimates near visual symptoms in children with normal binocular vision compared with symptoms caused by preferred near activities that require similar amplitudes of accommodation and convergence. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Toward Development of a Fibromyalgia Responder Index and Disease Activity Score: OMERACT Module Update

    PubMed Central

    Mease, PJ; Clauw, DJ; Christensen, R; Crofford, L; Gendreau, M; Martin, SA; Simon, L; Strand, V; Williams, DA; Arnold, LM

    2012-01-01

    Following development of the core domain set for fibromyalgia (FM) in OMERACT 7–9, the FM working group has progressed toward the development of an FM responder index and a disease activity score based on these domains, utilizing outcome indices of these domains from archived randomized clinical trials (RCTs) in FM. Possible clinical domains that could be included in a responder index and disease activity score include: pain, fatigue, sleep disturbance, cognitive dysfunction, mood disturbance, tenderness, stiffness, and functional impairment. Outcome measures for these domains demonstrate good to adequate psychometric properties, although measures of cognitive dysfunction need to be further developed. The approach used in the development of responder indices and disease activity scores for rheumatoid arthritis and ankylosing spondylitis represent heuristic models for our work, but FM is challenging in that there is no clear algorithm of treatment that defines disease activity based on treatment decisions, nor are there objective markers that define thresholds of severity or response to treatment. The process of developing candidate dichotomous responder definitions and continuous quantitative disease activity measures is described, as is participant discussion that transpired at OMERACT 10. Final results of this work will be published in a separate manuscript pending completion of analyses. PMID:21724721

  18. Fibromax-based nonalcoholic fatty liver disease in chronic obstructive pulmonary disease patients with obstructive sleep apnea: Methodological considerations

    PubMed Central

    Monneret, Denis

    2017-01-01

    The relationship between nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) has been well demonstrated, but remains to be evidenced in chronic obstructive pulmonary disease (COPD). Recently, Viglino et al. (Eur Respir J, 2017) attempted to determine the prevalence of liver fibrosis, steatosis and nonalcoholic steatohepatitis (NASH) in COPD patients, some of whom had OSA, basing the NAFLD diagnostic on three circulating biomarker-based liver scores: the FibroTest, SteatoTest and NashTest, from the Fibromax® panel. Among the main findings, the absence of OSA treatment emerged as independently associated with liver fibrosis and steatosis, when compared to effective treatment. However, besides the low number of treated patients, no polysomnographic respiratory data was provided, making it difficult to differentiate the impact of OSA from that of COPD in NAFLD prevalence. Furthermore, NAFLD diagnosis relied exclusively on circulating biomarker-based liver scores, without histological, imagery or other liver exploratory methods. Therefore, in this article, some methodological points are reminded and discussed, including the choice of OSA measurements, and the significance of ActiTest and AshTest scores from Fibromax® in this pathophysiological context. PMID:29225775

  19. Histopathological aspects of liver under variable food restriction: has the intense one-week food restriction a protective effect on non-alcoholic-fatty-liver-disease (NAFLD) development?

    PubMed

    Makovicky, Peter; Tumova, Eva; Volek, Zdenek; Makovicky, Pavol; Vodickova, Ludmila; Slyskova, Jana; Svoboda, Miroslav; Rejhova, Alexandra; Vodicka, Pavel; Samasca, Gabriel; Kralova, Alena; Nagy, Melinda; Mydlarova-Blascakova, Marta; Poracova, Jana

    2014-12-01

    Non-alcoholic-fatty-liver-disease (NAFLD) is a clinicopathologic entity characterized by a variety of hepatic injury patterns without significant alcohol use. It has a close association with obesity, so treatment includes weight loss, control of insulin sensitivity, interventions directed at inflammation and fibrosis. There is a certain relationship between the grade and duration of food restriction and hepatic function. The objective of this work was to describe the relationship between biochemistry, autoantibodies, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and liver morphology in experimental rabbit groups with food restriction as compared to controls with ad libitum food (ADL) income. The experiment was performed on a total of 24 rabbits of a weaning age of 25-81 days. The first group (R1) was restricted between 32 and 39 days of age to 50 g of food per rabbit a day. The second group (R2) was also restricted between 32 and 39 days, but the rabbits received 65 g of food per rabbit a day. At the end of the experiment, the blood and liver samples were collected at necropsy. NAFLD has developed in all three groups. There was any autoantibody positivity in all three groups. IGF-I is moderately higher in R1 and R2 group, as compared to the control group (P > 0.05). IGFBP-3 is without statistical significance in all three groups. Alkaline phosphatase (ALP) is the only liver biochemical parameter that has significantly increased following food restriction (P > 0.039). Single one-week restriction has any protective effect on NAFLD development. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. The Potential Effect of Chinese Herbal Formula Hongqijiangzhi Fang in Improving NAFLD: Focusing on NLRP3 Inflammasome and Gut Microbiota

    PubMed Central

    Liang, Shu; Zhang, Yupei; Deng, Yuanjun; He, Yifang; Liang, Yinji; Liang, Zien; Chen, Yanning; Tang, Kairui; Chen, Runsen

    2018-01-01

    The present study investigates the potential therapeutic mechanism underlying the effects of the Chinese herbal formula Hongqijiangzhi Fang (HJF) on nonalcoholic fatty liver disease (NAFLD) in rats. Male Sprague Dawley (SD) rats were randomly divided into 4 groups (n = 8): control group was fed a normal diet, three other groups were fed high-fat diets (HFD), and the two treatment groups were intragastrically given a compound probiotic or HJF during the molding time. After 16 w, related indices were detected. The results showed that HJF significantly reduced abdominal aorta serum cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), IL-1β, and IL-18, portal venous serum lipopolysaccharide (LPS), and liver TC and TG levels in HFD-fed rats. HJF ameliorated hepatic steatosis in the liver and improved the intestinal barrier in HFD-fed rats. Activation of the NLRP3 inflammasome was reduced by HJF in HFD-fed rats. Additionally, the abundances of A. muciniphila (Verrucomicrobiaceae), F. rappini (Helicobacteraceae), and Enterobacteriaceae bacteria significantly decreased in HJF-treated HFD-fed rats. In conclusion, these result suggested that the Chinese herbal formula HJF reduced hepatic steatosis maybe through decreasing certain gut bacteria (such as Enterobacteriaceae bacteria and F. rappini), alleviating intestinal endotoxemia and reducing NLRP3 inflammasome activation. PMID:29675053

  1. An observational study on the association between major dietary patterns and non-alcoholic fatty liver disease in Chinese adolescents

    PubMed Central

    Liu, Xiaonan; Peng, Yan; Chen, Shuhong; Sun, Qingyun

    2018-01-01

    Abstract Data on the association of dietary patterns with non-alcoholic fatty liver disease (NAFLD) among adolescents are scarce. Hence, the purpose of this study was to ascertain the influence of dietary patterns and key foods on NAFLD among adolescents in Shandong, China. Data were extracted from Linyi Nutrition and Health study during 2015 to 2016. This cross-sectional study population comprised 1639 participants aged between 16 and 23 years. Dietary intake was assessed by the use of a semiquantitative food frequency questionnaire (FFQ), containing 85 food items. NAFLD diagnosis was defined as individuals whose ultrasound examination disclosed hepatic steatosis at any stage, in the absence of excess intake of alcoholic beverages. The odds ratio (OR) and 95% confidence interval (CI) were estimated for each quartile of the dietary pattern adherence scores using logistic regression analysis. Of 1639 participants, 221 (13.5%) were classified as having NAFLD. Three major dietary patterns were derived from factor analysis: traditional Chinese, Western, and high-energy dietary patterns. There were significant differences in the intake of whole grains, tuber, and vegetable across quartiles of the traditional Chinese and Western pattern (P < .05). Besides, compared with adolescents in the lowest quartile, those in the highest quartile for whole grains intake had a lower OR for NAFLD (OR = 0.72; 95%CI: 0.61–0.98; P < .05), and for red meat and soft drink consumption had greater OR for NAFLD (OR = 1.34; 95% CI: 1.06–1.72; OR = 1.69; 95% CI: 1.34–2.56; respectively, P < .05). After adjustment for several potential confounders, participants in the highest quartile of the traditional Chinese pattern scores had lower OR for NAFLD (OR = 0.726; 95% CI: 0.383–0.960, P < .05) than did those in the lowest quartile, whereas those in the highest quartile of the Western pattern score had greater OR for NAFLD (OR = 1.197; 95% CI: 1.013–1

  2. Nonalcoholic fatty liver disease is associated with an increased risk of heart block in hospitalized patients with type 2 diabetes mellitus.

    PubMed

    Mantovani, Alessandro; Rigolon, Riccardo; Pichiri, Isabella; Bonapace, Stefano; Morani, Giovanni; Zoppini, Giacomo; Bonora, Enzo; Targher, Giovanni

    2017-01-01

    Recent studies suggested that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiac tachyarrhythmias (mainly atrial fibrillation) in patients with and without type 2 diabetes mellitus. The aim of this study was to examine whether an association also exists between NAFLD and heart block. We have retrospectively evaluated a hospital-based cohort of 751 patients with type 2 diabetes discharged from our Division of Diabetes and Endocrinology during years 2007-2014. Standard electrocardiograms were performed on all patients. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced hepatic fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis markers. Overall, 524 (69.8%) patients had NAFLD and 202 (26.9%) had heart block (defined as at least one block among first-degree atrio-ventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block) on electrocardiograms. Patients with NAFLD had a remarkably higher prevalence of any persistent heart block than those without NAFLD (31.3% vs. 16.7%, p<0.001); this prevalence was particularly increased among those with higher FIB-4 score. NAFLD was associated with a threefold increased risk of prevalent heart block (adjusted-odds ratio 3.04, 95% CI 1.81-5.10), independently of age, sex, hypertension, prior ischemic heart disease, hemoglobin A1c, microvascular complication status, use of medications and other potentially confounding factors. In conclusion, this is the largest cross-sectional study to show that NAFLD and its severity are independently associated with an increased risk of prevalent heart block in hospitalized patients with type 2 diabetes.

  3. Non-invasive Diagnosis of Fibrosis in Non-alcoholic Fatty Liver Disease

    PubMed Central

    Arora, Anil; Sharma, Praveen

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed as well as in developing countries. Its prevalence continues to rise currently affecting approximately 20-30% of adults and 10% of children in the United States. Non-alcoholic fatty liver disease represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign non-progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several non-invasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. There has been a substantial development of non-invasive risk scores, biomarker panels, and radiological modalities to identify at risk patients with NAFLD without recourse to liver biopsy on a routine basis. Examples include combination of serum markers like NAFLD fibrosis score (NFS), BARD score, fibrometer, FIB4, and non-invasive tools like fibroscan which assess fibrosis in patients with NAFLD. Other markers of fibrosis that have been evaluated include high-sensitivity C-reactive protein, plasma pentraxin 3, interleukin-6, and cytokeratin-18. This review focuses on the methods currently available in daily clinical practice in hepatology and touches briefly on the potential future markers under investigation. PMID:25755423

  4. The intake of high fat diet with different trans fatty acid levels differentially induces oxidative stress and non alcoholic fatty liver disease (NAFLD) in rats

    PubMed Central

    2011-01-01

    Background Trans-fatty acids (TFA) are known as a risk factor for coronary artery diseases, insulin resistance and obesity accompanied by systemic inflammation, the features of metabolic syndrome. Little is known about the effects on the liver induced by lipids and also few studies are focused on the effect of foods rich in TFAs on hepatic functions and oxidative stress. This study investigates whether high-fat diets with different TFA levels induce oxidative stress and liver dysfunction in rats. Methods Male Wistar rats were divided randomly into four groups (n = 12/group): C receiving standard-chow; Experimental groups that were fed high-fat diet included 20% fresh soybean oil diet (FSO), 20% oxidized soybean oil diet (OSO) and 20% margarine diet (MG). Each group was kept on the treatment for 4 weeks. Results A liver damage was observed in rats fed with high-fat diet via increase of liver lipid peroxidation and decreased hepatic antioxidant enzyme activities (superoxide dismutase, catalase and glutathione peroxidase). The intake of oxidized oil led to higher levels of lipid peroxidation and a lower concentration of plasma antioxidants in comparison to rats fed with FSO. The higher inflammatory response in the liver was induced by MG diet. Liver histopathology from OSO and MG groups showed respectively moderate to severe cytoplasm vacuolation, hypatocyte hypertrophy, hepatocyte ballooning, and necroinflammation. Conclusion It seems that a strong relationship exists between the consumption of TFA in the oxidized oils and lipid peroxidation and non alcoholic fatty liver disease (NAFLD). The extent of the peroxidative events in liver was also different depending on the fat source suggesting that feeding margarine with higher TFA levels may represent a direct source of oxidative stress for the organism. The present study provides evidence for a direct effect of TFA on NAFLD. PMID:21943357

  5. Greater emotional eating scores associated with reduced frontolimbic activation to palatable taste in adolescents.

    PubMed

    Bohon, Cara

    2014-08-01

    This study examined the relation between self-reported emotional eating scores and frontolimbic brain response to palatable taste in adolescents. Participants included 162 adolescents (mean BMI percentile = 52.7, range 3-90). Participants completed a self-report survey assessing emotional eating and underwent functional magnetic resonance imaging (fMRI) while viewing pictures signaling subsequent delivery of a chocolate milkshake or a control taste and receiving the corresponding taste. Results revealed no significant relation between emotional eating scores and brain response to anticipation of receipt of milkshake. In response to milkshake taste receipt, emotional eating scores were negatively related to activation in the right thalamus, the left insula and orbitofrontal cortex, and bilateral putamen and caudate. These findings remained significant after controlling for body mass index and body fat percentage. The current results are discussed in the context of findings of reduced reward activation to palatable taste receipt in obese adults and adolescents. Copyright © 2014 The Obesity Society.

  6. Prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the United States.

    PubMed

    Le, Michael H; Devaki, Pardha; Ha, Nghiem B; Jun, Dae Won; Te, Helen S; Cheung, Ramsey C; Nguyen, Mindie H

    2017-01-01

    In the United States, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and associated with higher mortality according to data from earlier National Health and Nutrition Examination Survey (NHANES) 1988-1994. Our goal was to determine the NAFLD prevalence in the recent 1999-2012 NHANES, risk factors for advanced fibrosis (stage 3-4) and mortality. NAFLD was defined as having a United States Fatty Liver Index (USFLI) > 30 in the absence of heavy alcohol use and other known liver diseases. The probability of low/high risk of having advanced fibrosis was determined by the NAFLD Fibrosis Score (NFS). In total, 6000 persons were included; of which, 30.0% had NAFLD and 10.3% of these had advanced fibrosis. Five and eight-year overall mortality in NAFLD subjects with advanced fibrosis was significantly higher than subjects without NAFLD ((18% and 35% vs. 2.6% and 5.5%, respectively) but not NAFLD subjects without advanced fibrosis (1.1% and 2.8%, respectively). NAFLD with advanced fibrosis (but not those without) is an independent predictor for mortality on multivariate analysis (HR = 3.13, 95% CI 1.93-5.08, p<0.001). In conclusion, in this most recent NHANES, NAFLD prevalence remains at 30% with 10.3% of these having advanced fibrosis. NAFLD per se was not a risk factor for increased mortality, but NAFLD with advanced fibrosis was. Mexican American ethnicity was a significant risk factor for NAFLD but not for advanced fibrosis or increased mortality.

  7. Stage of change and motivation to healthier lifestyle in non-alcoholic fatty liver disease.

    PubMed

    Centis, Elena; Moscatiello, Simona; Bugianesi, Elisabetta; Bellentani, Stefano; Fracanzani, Anna Ludovica; Calugi, Simona; Petta, Salvatore; Dalle Grave, Riccardo; Marchesini, Giulio

    2013-04-01

    Healthy diet and physical activity are the treatment cornerstones of non-alcoholic fatty liver disease (NAFLD); their effectiveness is however limited by difficulties in implementing lifestyle changes. We aimed at determining the stage of change and associated psychological factors as a prerequisite to refine strategies to implement behavior changes. We studied 138 consecutive NAFLD patients (73% male, age 19-73 years). The diagnosis was confirmed by liver biopsy in 64 cases (steatohepatitis, 47%). All cases completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments (for diet and physical activity, respectively) and providing stages of change according to transtheoretical model. Logistic regression analysis was used to identify factors associated with stages making behavioral changes more demanding. The individual profiles were variable; for diet, no cases had precontemplation as prevalent stage of change (highest score in individual profiles); 36% had contemplation. For physical activity, 50% were classified in either precontemplation or contemplation. Minor differences were recorded in relation to associated metabolic complications or steatohepatitis. Logistic regression identified male sex (odds ratio, 4.51; 95% confidence interval, 1.69-12.08) and age (1.70; 1.20-2.43 per decade) as the independent parameters predicting precontemplation or contemplation for diet. No predictors were identified for physical activity. NAFLD cases have scarce readiness to lifestyle changes, particularly with regard to physical activity. Defining stages of change and motivation offers the opportunity to improve clinical care of NAFLD people through individual programs exploiting the powerful potential of behavioral counseling, an issue to be tested in longitudinal studies. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  8. Capsule Endoscopy Crohn's Disease Activity Index (CECDAIic or Niv Score) for the Small Bowel and Colon.

    PubMed

    Niv, Yaron; Gal, Eyal; Gabovitz, Violeta; Hershkovitz, Marcela; Lichtenstein, Lev; Avni, Irit

    2018-01-01

    Crohn's disease (CD) is a chronic inflammatory disorder defined as a transmural inflammation of the bowel wall, affecting the small and large intestine. The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity. We extended the Niv score to the colon and have a comprehensive view of the whole intestine. We evaluated 3 parameters of intestinal pathology: A, Inflammation; B, Extent of disease; C, Presence of strictures. The scoring formula is as follows: CEDCAIic=(A1×B1+C1)+(A2×B2+C2)+(A3×B3+C3)+(A4×B4+C4) (1=proximal small bowel, 2=distal small bowel, 3=right colon, 4=left colon). The median CECDAIic score was 15.5 (range, 0 to 42), and the mean±SD score was 17.2±11.5. The CECDAIic scores per patient were similar among the 5 observers. Kendall's coefficient of concordance was high and significant for almost all the parameters examined except for strictures in the proximal small bowel and distal colon. Nevertheless, the coefficients for the small bowel and for the whole intestine were high, 0.85 and 0.77, P<0.0001, respectively. We established a new score, the CECDAIic of the small-bowel and colonic CD. We offer this easy, user-friendly score for use in randomized controlled trials and in the clinical follow-up of CD patients.

  9. Treating Obstructive Sleep Apnea and Chronic Intermittent Hypoxia Improves the Severity of Nonalcoholic Fatty Liver Disease in Children.

    PubMed

    Sundaram, Shikha S; Halbower, Ann C; Klawitter, Jelena; Pan, Zhaoxing; Robbins, Kristen; Capocelli, Kelley E; Sokol, Ronald J

    2018-07-01

    To determine the effects of treating obstructive sleep apnea/nocturnal hypoxia on pediatric nonalcoholic fatty liver disease (NAFLD) severity and oxidative stress. Biopsy proven participants (n = 9) with NAFLD and obstructive sleep apnea/hypoxia were studied before and after treatment with continuous positive airway pressure (CPAP) for sleep disordered breathing, including laboratory testing and markers of oxidative stress, urine F(2)-isoprostanes. Adolescents (age 11.5 ± 1.2 years; body mass index, 29.5 ± 3.8 kg/m 2 ) with significant NAFLD (mean histologic necroinflammation grade, 2.3 ± 0.9; fibrosis stage, 1.4 ± 1.3; NAFLD Activity Score summary, 4.8 ± 1.6) had obstructive sleep apnea/hypoxia by polysomnography. At baseline, they had severe obstructive sleep apnea/hypoxia, elevated aminotransferases, the metabolic syndrome, and significant oxidative stress (high F(2)-isoprostanes). Obstructive sleep apnea/hypoxia was treated with home CPAP for a mean 89 ± 62 days. Although body mass index increased, obstructive sleep apnea/hypoxia severity improved on CPAP and was accompanied by reduced alanine aminotransferase, metabolic syndrome markers, and F(2)-isoprostanes. This study provides strong evidence that treatment of obstructive sleep apnea/nocturnal hypoxia with CPAP in children with NAFLD may reverse parameters of liver injury and reduce oxidative stress. These data also suggest CPAP as a new therapy to prevent progression of NAFLD in those children with obesity found to have obstructive sleep apnea/nocturnal hypoxia. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial

    PubMed Central

    Eckard, Carly; Cole, Renee; Lockwood, Joshua; Torres, Dawn M.; Williams, Christopher D.; Shaw, Janet C.

    2013-01-01

    Background and aims: Nonalcoholic fatty liver disease (NAFLD) is now recognized as part of the metabolic syndrome, and is specifically related to obesity and insulin resistance. Lifestyle modification is advocated for the treatment of NAFLD, but few studies have evaluated its impact on liver histology. The purpose of this study was to investigate which, if any, specific diet and exercise recommendations are associated with histopathologic changes. Methods: A total of 56 participants were randomly assigned to 1 of 4 lifestyle modification subgroups for 6 months: standard care, low-fat diet and moderate exercise, moderate-fat/low-processed-carbohydrate diet and moderate exercise, or moderate exercise only. All subjects had biopsy-proven NAFLD, to include nonalcoholic steatohepatitis (NASH), and received a repeat 6-month biopsy to detect histopathologic changes. Other measures included blood assay of liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), fasting glucose, serum insulin, lipid panel, body weight, dietary intake, fat mass, and fitness level. Results: Among the 41 participants who completed the study (88% with NASH), a significant change was found in pre- to post-NAFLD activity score in the group as a whole (p < 0.001) with no difference detected between subgroups (p = 0.31). Our results confirm that lifestyle modification is effective in improving NAFLD and NASH. Conclusions: Regardless of intervention group, lifestyle modification improved liver histology, as verified by repeat biopsy, after a 6-month intervention. This study reinforces the importance of lifestyle modification as the primary treatment strategy for patients with NAFLD. PMID:23814606

  11. Exercise dependence score in patients with longstanding eating disorders and controls: the importance of affect regulation and physical activity intensity.

    PubMed

    Bratland-Sanda, Solfrid; Martinsen, Egil W; Rosenvinge, Jan H; Rø, Oyvind; Hoffart, Asle; Sundgot-Borgen, Jorunn

    2011-01-01

    To examine associations among exercise dependence score, amount of physical activity and eating disorder (ED) symptoms in patients with longstanding ED and non-clinical controls. Adult female inpatients (n = 59) and 53 age-matched controls participated in this cross sectional study. Assessments included the eating disorders examination, eating disorders inventory, exercise dependence scale, reasons for exercise inventory, and MTI Actigraph accelerometer. Positive associations were found among vigorous, not moderate, physical activity, exercise dependence score and ED symptoms in patients. In the controls, ED symptoms were negatively associated with vigorous physical activity and not correlated with exercise dependence score. Exercise for negative affect regulation, not weight/appearance, and amount of vigorous physical activity were explanatory variables for exercise dependence score in both groups. The positive associations among exercise dependence score, vigorous physical activity and ED symptoms need proper attention in the treatment of longstanding ED. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.

  12. Nonalcoholic fatty liver disease associated with metabolic syndrome: Influence of liver fibrosis stages on characteristics of very low-density lipoproteins.

    PubMed

    Lucero, Diego; Miksztowicz, Verónica; Gualano, Gisela; Longo, Cristina; Landeira, Graciela; Álvarez, Estela; Zago, Valeria; Brites, Fernando; Berg, Gabriela; Fassio, Eduardo; Schreier, Laura

    2017-10-01

    We evaluated possible changes in VLDLcharacteristics, and metabolic related factors, in MetS-associated NAFLD and accompanying liver fibrosis. We studied 36 MetS patients with biopsy-proven NAFLD (MetS+NAFLD) and 24 MetS without ultrasound NAFLD evidence. Further, MetS+NAFLD was sub-divided according to fibrosis stage into, non-to-moderate (F0-F2, n=27) and severe (F3-F4, n=9) fibrosis. We measured: lipid profile, VLDL composition and size (size exclusion-HPLC), CETP and lipoprotein lipase (LPL) activities and adiponectin. Additionally, in MetS+NAFLD type IV collagen 7S domain was measured. MetS+NAFLD showed increased VLDL-mass, VLDL particle number, VLDL-triglyceride% and large VLDL-% (p<0.04). CETP activity tended to increase in MetS+NAFLD (p=0.058), while LPL activity was unchanged. Moreover, in MetS+NAFLD, adiponectin was decreased (p<0.001), and negatively correlated with VLDL-mass and VLDL particle number (p<0.05), independently of insulin-resistance. Within MetS+NAFLD group, despite greater insulin-resistance, patients with severe fibrosis showed lower plasma triglycerides, VLDL-mass, VLDL-triglyceride%, large VLDL-% and CETP activity (p<0.05), while type IV collagen was increased (p=0.009) and inversely correlated with large VLDL-% (p=0.045). In MetS, NAFLD is associated with larger and triglyceride over-enriched circulating VLDLs, of greater atherogenicity. However, when NAFLD progresses to severe fibrosis, circulating VLDL features apparently improved, probably due to early alterations in hepatic synthetic function. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Auditory short-term memory activation during score reading.

    PubMed

    Simoens, Veerle L; Tervaniemi, Mari

    2013-01-01

    Performing music on the basis of reading a score requires reading ahead of what is being played in order to anticipate the necessary actions to produce the notes. Score reading thus not only involves the decoding of a visual score and the comparison to the auditory feedback, but also short-term storage of the musical information due to the delay of the auditory feedback during reading ahead. This study investigates the mechanisms of encoding of musical information in short-term memory during such a complicated procedure. There were three parts in this study. First, professional musicians participated in an electroencephalographic (EEG) experiment to study the slow wave potentials during a time interval of short-term memory storage in a situation that requires cross-modal translation and short-term storage of visual material to be compared with delayed auditory material, as it is the case in music score reading. This delayed visual-to-auditory matching task was compared with delayed visual-visual and auditory-auditory matching tasks in terms of EEG topography and voltage amplitudes. Second, an additional behavioural experiment was performed to determine which type of distractor would be the most interfering with the score reading-like task. Third, the self-reported strategies of the participants were also analyzed. All three parts of this study point towards the same conclusion according to which during music score reading, the musician most likely first translates the visual score into an auditory cue, probably starting around 700 or 1300 ms, ready for storage and delayed comparison with the auditory feedback.

  14. Auditory Short-Term Memory Activation during Score Reading

    PubMed Central

    Simoens, Veerle L.; Tervaniemi, Mari

    2013-01-01

    Performing music on the basis of reading a score requires reading ahead of what is being played in order to anticipate the necessary actions to produce the notes. Score reading thus not only involves the decoding of a visual score and the comparison to the auditory feedback, but also short-term storage of the musical information due to the delay of the auditory feedback during reading ahead. This study investigates the mechanisms of encoding of musical information in short-term memory during such a complicated procedure. There were three parts in this study. First, professional musicians participated in an electroencephalographic (EEG) experiment to study the slow wave potentials during a time interval of short-term memory storage in a situation that requires cross-modal translation and short-term storage of visual material to be compared with delayed auditory material, as it is the case in music score reading. This delayed visual-to-auditory matching task was compared with delayed visual-visual and auditory-auditory matching tasks in terms of EEG topography and voltage amplitudes. Second, an additional behavioural experiment was performed to determine which type of distractor would be the most interfering with the score reading-like task. Third, the self-reported strategies of the participants were also analyzed. All three parts of this study point towards the same conclusion according to which during music score reading, the musician most likely first translates the visual score into an auditory cue, probably starting around 700 or 1300 ms, ready for storage and delayed comparison with the auditory feedback. PMID:23326487

  15. Development of Serum Marker Models to Increase Diagnostic Accuracy of Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: The New LINKI Algorithm Compared with Established Algorithms.

    PubMed

    Lykiardopoulos, Byron; Hagström, Hannes; Fredrikson, Mats; Ignatova, Simone; Stål, Per; Hultcrantz, Rolf; Ekstedt, Mattias; Kechagias, Stergios

    2016-01-01

    Detection of advanced fibrosis (F3-F4) in nonalcoholic fatty liver disease (NAFLD) is important for ascertaining prognosis. Serum markers have been proposed as alternatives to biopsy. We attempted to develop a novel algorithm for detection of advanced fibrosis based on a more efficient combination of serological markers and to compare this with established algorithms. We included 158 patients with biopsy-proven NAFLD. Of these, 38 had advanced fibrosis. The following fibrosis algorithms were calculated: NAFLD fibrosis score, BARD, NIKEI, NASH-CRN regression score, APRI, FIB-4, King´s score, GUCI, Lok index, Forns score, and ELF. Study population was randomly divided in a training and a validation group. A multiple logistic regression analysis using bootstrapping methods was applied to the training group. Among many variables analyzed age, fasting glucose, hyaluronic acid and AST were included, and a model (LINKI-1) for predicting advanced fibrosis was created. Moreover, these variables were combined with platelet count in a mathematical way exaggerating the opposing effects, and alternative models (LINKI-2) were also created. Models were compared using area under the receiver operator characteristic curves (AUROC). Of established algorithms FIB-4 and King´s score had the best diagnostic accuracy with AUROCs 0.84 and 0.83, respectively. Higher accuracy was achieved with the novel LINKI algorithms. AUROCs in the total cohort for LINKI-1 was 0.91 and for LINKI-2 models 0.89. The LINKI algorithms for detection of advanced fibrosis in NAFLD showed better accuracy than established algorithms and should be validated in further studies including larger cohorts.

  16. International physical activity questionnaire overestimation is ameliorated by individual analysis of the scores.

    PubMed

    Bermúdez, Valmore J; Rojas, Joselyn J; Córdova, Evelyn B; Añez, Roberto; Toledo, Alexandra; Aguirre, Miguel A; Cano, Climaco; Arraiz, Nailet; Velasco, Manuel; López-Miranda, José

    2013-01-01

    Sedentarism is considered a risk factor for coronary heart disease and death from any cardiovascular disease. The International Physical Activity Questionnaire (IPAQ) assesses physical activity in metabolic equivalents, using 4 dimensions: occupation, transportation, household activities, and leisure-time physical activity. The purpose of this investigation was to assess physical activity levels in the patients enrolled in the Maracaibo City Metabolic Syndrome Prevalence Study, currently undertaken by the "Dr. Félix Gómez" Endocrine-Metabolic Research Center. Two thousand one hundred eight individuals were recruited and subjected to a standard Medical chart, Graffar scale, and IPAQ long form, applied by trained personnel. Description of the population was done using mean, SD, and coefficient of variation. IPAQ scores were analyzed as medians and distributed by percentiles. From the 2108 individuals, 46.9% were men and 53.1% were women. The most prevalent physical activity was high physical activity with 39.9%, followed by moderate physical activity with 36.9% and low physical activity with 23.2%. Medians for each IPAQ dominion were occupation with 0.00 (0.00-66.00), transportation with 165.00 (0.00-463.00), household activities with 772.50 (0.00-2520.00), and leisure time with 0.00 (0.00-594.00). Using leisure-time scores, a new reclassification was conducted, obtaining 1245 subjects with 0 metabolic equivalents in this dominion. From this new subsample, 43.6% had High physical activity, 56.95% had Moderate physical activity, and 91% had Low physical activity, demonstrating an important overestimation in the former sample results. IPAQ overestimates moderate and vigorous activity in the adult population of the Maracaibo Municipality. Overestimation is mainly located in the household- and gardening-related activity.

  17. Protective Effects and Mechanism of Meretrix meretrix Oligopeptides against Nonalcoholic Fatty Liver Disease

    PubMed Central

    Huang, Fangfang; Zhao, Shasha; Yu, Fangmiao; Yang, Zuisu; Ding, Guofang

    2017-01-01

    Meretrix meretrix oligopeptides (MMO) derived from shellfish have important medicinal properties. We previously obtained MMO from alcalase by hydrolysis processes. Here we examine the protective effects of MMO against nonalcoholic fatty liver disease (NAFLD) and explored the underlying mechanism. Human Chang liver cells were used in our experiments after exposure to palmitic acid at a final concentration of 15 μg/mL for 48 h to induce an overload of fatty acid as NAFLD model cells. Treatment with MMO for 24 h increased the viability of the NAFLD model cells by inhibiting apoptosis. MMO alleviated oxidative stress in the NAFLD model cells by preserving reactive oxygen species activity and increasing malondialdehyde and superoxide dismutase activity. MMO improved mitochondrial dysfunction by decreasing the mitochondrial membrane potential and increasing the activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase. In addition, MMO inhibited the activation of cell death-related pathways, based on reduced p-JNK, Bax expression, tumor necrosis factor-α, caspase-9, and caspase-3 activity in the NAFLD model cells, and Bcl-2 expression was enhanced in the NAFLD model cells compared with the control group. These findings indicate that MMO have antioxidant and anti-apoptotic effects on NAFLD model cells and may thus exert protective effects against NAFLD. PMID:28216552

  18. Does propolis have any effect on non-alcoholic fatty liver disease?

    PubMed

    Kismet, Kemal; Ozcan, Cigdem; Kuru, Serdar; Gencay Celemli, Omur; Celepli, Pinar; Senes, Mehmet; Guclu, Tuncay; Sorkun, Kadriye; Hucumenoglu, Sema; Besler, Tanju

    2017-06-01

    The aim of this study was to evaluate the therapeutic effect of propolis on non-alcoholic fatty liver disease (NAFLD) in rats. The rats were randomly divided into 3 groups of 10 as the NAFLD, NAFLD+100 and NAFLD+200 groups. The rats were fed with a fatty diet (25g/kg/day) to provoke NAFLD. Then after the formation of fatty liver, a standard diet (SD) (25g/kg/day) was given to the NAFLD group and the other two groups were fed with SD and 100mg/kg (NAFLD+100 Group) or 200mg/kg propolis (NAFLD+200 Group) for two weeks. At the end of two weeks the animals were sacrificed. Blood and tissue samples were taken for biochemical and histopathological evaluations. The propolis-treated groups had better results in serum lipids (total cholesterol, non-HDL cholesterol, triglyceride), ALT, and ALP values. When compared with the NAFLD group, IL-6 and TNF-α values decreased in the NAFLD+100 and NAFLD+200 groups. The administration of propolis to the rats significantly reduced serum and tissue MDA and GPX values and increased SH in serum when compared with the NAFLD group. No difference was determined between the groups treated with two different doses of propolis in respect of biochemical values. When the mean histological scores of the groups were compared, statistically significant differences were found between the NAFLD group and the propolis-treated groups. No difference was determined between the groups treated with the two different doses of propolis in respect of histopathological results. Propolis had positive effects on histopathological and biochemical parameters of NAFLD and these effects were related to the anti-oxidant and anti-inflammatory effects of propolis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Genetic parameter estimates among scale activity score and farrowing disposition with reproductive traits in swine.

    PubMed

    Schneider, J F; Rempel, L A; Rohrer, G A; Brown-Brandl, T M

    2011-11-01

    The primary objective of this study was to determine if certain behavior traits were genetically correlated with reproduction. If 1 or both of the behavior traits were found to be correlated, a secondary objective was to determine if the behavior traits could be useful in selecting for more productive females. A scale activity score taken at 5 mo of age and a farrowing disposition score taken at farrowing were selected as the behavioral traits. Scale activity score ranged from 1 to 5 and farrowing disposition ranged from 1 to 3. Reproductive traits included age at puberty, number born alive, number born dead, litter birth weight, average piglet birth weight, number weaned, litter weaning weight, average weaning weight, wean-to-estrus interval, ovulation rate including gilts, and postweaning ovulation rate. Genetic correlations between scale activity score and reproduction ranged from -0.79 to 0.61. Three of the correlations, number born alive (P < 0.01), average piglet birth weight (P < 0.001), and wean-to-estrus interval (P = 0.014), were statistically significant but included both favorable and antagonistic correlations. In contrast, all but 1 of the farrowing disposition correlations was favorable and ranged from -0.66 to 0.67. Although only the correlation with litter birth weight was significant (P = 0.018), the consistent favorable direction of all farrowing disposition correlations, except average weaning weight, shows a potential for inclusion of farrowing disposition into a selection program.

  20. The association of sleep duration and sleep quality with non-alcoholic fatty liver disease in a Taiwanese population.

    PubMed

    Chou, Yu-Tsung; Cheng, Hsiang-Ju; Wu, Jin-Shang; Yang, Yi-Ching; Chou, Chieh-Ying; Chang, Chih-Jen; Lu, Feng-Hwa

    2018-06-18

    The association of sleep duration/quality with nonalcoholic fatty liver disease (NAFLD) is inconclusive. Several important covariates were not adjusted concomitantly in some studies, and the severity of NAFLD was not considered. Furthermore, the gender impact of sleep duration or sleep quality on NAFLD remains unclear. We thus aimed to examine the association of sleep duration and quality with NAFLD by gender in a Taiwanese population. A total of 6663 subjects aged 18 years or more were enrolled. The severity of NAFLD was divided into mild, moderate, and severe degrees based on ultrasound findings. The sleep duration was classified into three groups: short (<6h), normal (6-8h), and long (>8h). Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and poor sleep quality was defined as a global PSQI score greater than 5. After adjustment for potential confounders, multinomial logistic regression showed that poor sleep quality was negatively associated with both mild and moderate-to-severe NAFLD in males, but sleep duration was not independently related to NAFLD. In females, sleep condition was not related to NAFLD. Poor sleep quality but not sleep duration was associated with a lower risk of not only moderate to severe but also mild NAFLD in males. In females, the association of sleep quality and duration with the risk of NAFLD was insignificant. Copyright © 2018 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  1. [Prevalence of no alcohol fatty liver disease (NAFLD) in a population of obese children in Valencia, Venezuela].

    PubMed

    Pontiles de Sánchez, Milagros; Morón de Salim, Alba; Rodríguez de Perdomo, Henny; Perdomo Oramas, Germán

    2014-06-01

    No Alcoholic Fatty Liver Disease (NAFLD) is characterized by an abnormal accumulation of fat in hepatocytes, without alcohol, where overweight and obesity are determinants. Ecosonografia evaluated the prevalence of fatty liver in obese pediatric patients and its relation to nutritional assessment. The sample consisted of 85 children (51 females, 34 males), age 3-17. The abdominal ecosonography, BMI, waist circumference were performed; Godard Test for physical activity, history of diabetes, dyslipidemia, obesity and cardiovascular disease were questioned. Lipid profile, glucose and insulin resistance were determined. Data analyzed from descriptive and comparative tables. We obtained: mean age 9.8 ± 2.7 females and males 9.6 ± 2.7 years. The ecosonography indicated 50% and 50% fatty liver-pancreas fatty liver in children aged 3-6 years; 7-11 years 39.7% fatty liver-pancreas; 12-17yrs 31.6% fatty liver-pancreas (p > 0.05); BMI > 26 kg/m2 42.9% fatty liver-pancreas; 21 to 25 kg/m2 44.7% fatty liver; 15 to 20 kg/m2 60%fatty liver-pancreas (p> 0.05). 97.6% with high CC; 68.2% with inadequate physical activity; high frequency of history of chronic non-communicable diseases. We concluded that this population had predominantly fatty liver fatty replacement of the pancreas (HG-RGP) in the groups with higher BMI, CC and high male unrelated insulin resistance, altered lipid profile and diagnosis HG. We inferred that the anthropometric assessment of waist circumference and abdominal ecosonography indicate the presence of visceral obesity, a condition that predisposes to hepatic steatosis, pancreas and/or liver-pancreas.

  2. The effect of routine hoof trimming on locomotion score, ruminating time, activity, and milk yield of dairy cows.

    PubMed

    Van Hertem, T; Parmet, Y; Steensels, M; Maltz, E; Antler, A; Schlageter-Tello, A A; Lokhorst, C; Romanini, C E B; Viazzi, S; Bahr, C; Berckmans, D; Halachmi, I

    2014-01-01

    The objective of this study was to quantify the effect of hoof trimming on cow behavior (ruminating time, activity, and locomotion score) and performance (milk yield) over time. Data were gathered from a commercial dairy farm in Israel where routine hoof trimming is done by a trained hoof trimmer twice per year on the entire herd. In total, 288 cows spread over 6 groups with varying production levels were used for the analysis. Cow behavior was measured continuously with a commercial neck activity logger and a ruminating time logger (HR-Tag, SCR Engineers Ltd., Netanya, Israel). Milk yield was recorded during each milking session with a commercial milk flow sensor (Free Flow, SCR Engineers Ltd.). A trained observer assigned on the spot 5-point locomotion scores during 19 nighttime milking occasions between 22 October 2012 and 4 February 2013. Behavioral and performance data were gathered from 1wk before hoof trimming until 1wk after hoof trimming. A generalized linear mixed model was used to statistically test all main and interactive effects of hoof trimming, parity, lactation stage, and hoof lesion presence on ruminating time, neck activity, milk yield, and locomotion score. The results on locomotion scores show that the proportional distribution of cows in the different locomotion score classes changes significantly after trimming. The proportion of cows with a locomotion score ≥3 increases from 14% before to 34% directly after the hoof trimming. Two months after the trimming, the number of cows with a locomotion score ≥3 reduced to 20%, which was still higher than the baseline values 2wk before the trimming. The neck activity level was significantly reduced 1d after trimming (380±6 bits/d) compared with before trimming (389±6 bits/d). Each one-unit increase in locomotion score reduced cow activity level by 4.488 bits/d. The effect of hoof trimming on ruminating time was affected by an interaction effect with parity. The effect of hoof trimming on

  3. High prevalence of apolipoprotein B dyslipoproteinemias in non-alcoholic fatty liver disease: The lifelines cohort study.

    PubMed

    Nass, Karlijn J; van den Berg, Eline H; Faber, Klaas Nico; Schreuder, Tim C M A; Blokzijl, Hans; Dullaart, Robin P F

    2017-07-01

    Cardiovascular disease (CVD) is a major adverse consequence of non-alcoholic fatty liver disease (NAFLD). The association of NAFLD with various apolipoprotein B (apoB) dyslipoproteinemias is unclear. We determined the prevalence of specific apoB dyslipoproteinemias in subjects with suspected NAFLD. This study was conducted among 22,865 fasting adults living in the northern part of the Netherlands (Lifelines Cohort Study). Six apoB dyslipoproteinemias were defined using an algorithm derived from apoB, total cholesterol and triglycerides. NAFLD was defined as Fatty Liver Index (FLI) ≥60. Advanced hepatic fibrosis was defined as NAFLD fibrosis score (NFS) ≥0.676. 4790 participants (20.9%) had an FLI≥60. NAFLD subjects were older, more likely to be men, more obese and more often had diabetes and metabolic syndrome (P<0.001 for each). Among NAFLD subjects, any apoB dyslipoproteinemia was present in 61.5% vs. 16.5% in subjects without NAFLD (P<0.001). Elevated chylomicrons were not observed in NAFLD. In univariate analysis, NAFLD was associated with a higher prevalence of each apoB dyslipoproteinemia vs. subjects with an FLI<60 (P<0.001), except for low density lipoprotein (LDL) dyslipoproteinemia. Additionally, each apoB dyslipoproteinemia was independently associated with NAFLD in age- and sex-adjusted logistic regression analysis, including the apoB dyslipoproteinemias together (P<0.001). The prevalence of apoB dyslipoproteinemias was not altered in subjects with NFS ≥0.676. NAFLD rather than advanced hepatic fibrosis is independently associated with increased prevalence of chylomicrons+very low-density lipoproteins (VLDL) remnants, VLDL, LDL and VLDL+LDL dyslipoproteinemias. ApoB dyslipoproteinemias may contribute to increased CVD risk associated with NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Helicobacter pylori infection is not associated with nonalcoholic fatty liver disease

    PubMed Central

    Baeg, Myong Ki; Yoon, Seung Kew; Ko, Sun-Hye; Noh, Yong-Sun; Lee, In-Seok; Choi, Myung-Gyu

    2016-01-01

    AIM: To determine whether Helicobacter pylori (H. pylori) infection confers a higher risk of Nonalcoholic fatty liver disease (NAFLD). METHODS: Healthy people who underwent health screening were analyzed retrospectively. Inclusion criteria were age ≥ 20 years, history of H. pylori infection, and recorded insulin level. Participants were classified as H. pylori positive or negative according to 13C urea breath tests. NAFLD was defined using the hepatic steatosis index (HSI) and NAFLD liver fat score (NAFLD-LFS). Those with an HSI > 36 or NAFLD-LFS > -0.640 were considered to have NAFLD. Multivariable logistic regression was performed to identify risk factors for NAFLD. RESULTS: Three thousand six hundred and sixty-three people were analyzed and 1636 (44.7%) were H. pylori positive. H. pylori infection was associated with older age, male gender, hypertension, higher body mass index, and a dyslipidemic profile. HSI differed significantly between H. pylori positive and negative subjects (median 33.2, interquartile range (IQR) 30.0-36.2 for H. pylori-positive vs median 32.6, IQR 29.8-36.0 for negative participants, P = 0.005), but NAFLD-LSF did not [median -1.7, IQR -2.4 - -0.7 vs median -1.8, IQR -2.4-(-0.7), respectively, P = 0.122]. The percentage of people with NAFLD did not differ between infected and uninfected groups: HIS, 26.9% vs 27.1%, P = 0.173; NAFLD-LFS, 23.5% vs 23.1%, P = 0.778. H. pylori infection was not a risk factor, but C-reactive protein concentration and smoking were significant risk factors for NAFLD. CONCLUSION: H. pylori infection is not a risk factor for NAFLD as indicated by HSI or NAFLD-LFS. Prospective, large-scale studies involving liver biopsies should be considered. PMID:26937147

  5. A Nutrigenomic Approach to Non-Alcoholic Fatty Liver Disease.

    PubMed

    Dongiovanni, Paola; Valenti, Luca

    2017-07-16

    Following the epidemics of obesity due to the consumption of high-calorie diet and sedentary lifestyle, nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in Western countries. NAFLD is epidemiologically associated with metabolic syndrome and insulin resistance, and in susceptible individuals it may progress to cirrhosis and hepatocellular carcinoma. Genetic factors play a key role in NAFLD predisposition by interacting with nutritional and other environmental factors. To date, there is no drug therapy for the treatment of NAFLD, and the main clinical recommendation is lifestyle modification. In the last years, nutrigenomics is promoting an increased understanding of how nutrition affects the switch from health to disease by altering the expression of an individual's genetic makeup. The present review tries to summarize the most recent data evidencing how the interactions between nutrients and genetic factors can influence NAFLD development. The final goal should be to develop tools to quantify these complex interactions. The definition of a "nutrigenomic risk score" for each individual may represent a novel therapeutic approach for the management of NAFLD patients.

  6. Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease

    PubMed Central

    Lee, Hyun Jung; Yeon, Jong Eun; Ko, Eun Jung; Yoon, Eileen L; Suh, Sang Jun; Kang, Keunhee; Kim, Hae Rim; Kang, Seoung Hee; Yoo, Yang Jae; Je, Jihye; Lee, Beom Jae; Kim, Ji Hoon; Seo, Yeon Seok; Yim, Hyung Joon; Byun, Kwan Soo

    2015-01-01

    AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models. METHODS: Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-δ agonist (GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide (LPS), HFD + LPS + GW group]. HepG2 cells were exposed to palmitic acid (PA) and/or LPS in the absence or presence of GW. RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin (IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In HepG2 cells, PA and LPS treatment markedly increased mRNA of several nucleotide-binding and oligomerization domain-like receptor family members (NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α. CONCLUSION: PPAR-δ agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD. PMID:26668503

  7. Average vs item response theory scores: an illustration using neighbourhood measures in relation to physical activity in adults with arthritis.

    PubMed

    Mielenz, T J; Callahan, L F; Edwards, M C

    2017-01-01

    Our study had two main objectives: 1) to determine whether perceived neighbourhood physical features are associated with physical activity levels in adults with arthritis; and 2) to determine whether the conclusions are more precise when item response theory (IRT) scores are used instead of average scores for the perceived neighbourhood physical features scales. Information on health outcomes, neighbourhood characteristics, and physical activity levels were collected using a telephone survey of 937 participants with self-reported arthritis. Neighbourhood walkability and aesthetic features and physical activity levels were measured by self-report. Adjusted proportional odds models were constructed separately for each neighbourhood physical features scale. We found that among adults with arthritis, poorer perceived neighbourhood physical features (both walkability and aesthetics) are associated with decreased physical activity level compared to better perceived neighbourhood features. This association was only observed in our adjusted models when IRT scoring was employed with the neighbourhood physical feature scales (walkability scale: odds ratio [OR] 1.20, 95% confidence interval [CI] 1.02, 1.41; aesthetics scale: OR 1.32, 95% CI 1.09, 1.62), not when average scoring was used (walkability scale: OR 1.14, 95% CI 1.00, 1.30; aesthetics scale: OR 1.16, 95% CI 1.00, 1.36). In adults with arthritis, those reporting poorer walking and aesthetics features were found to have decreased physical activity levels compared to those reporting better features when IRT scores were used, but not when using average scores. This study may inform public health physical environmental interventions implemented to increase physical activity, especially since arthritis prevalence is expected to be close to 20% of the population in 2020. Based on NIH initiatives, future health research will utilize IRT scores. The differences found in this study may be a precursor for research on how past

  8. Male 11β-HSD1 Knockout Mice Fed Trans-Fats and Fructose Are Not Protected From Metabolic Syndrome or Nonalcoholic Fatty Liver Disease.

    PubMed

    Larner, Dean P; Morgan, Stuart A; Gathercole, Laura L; Doig, Craig L; Guest, Phil; Weston, Christopher; Hazeldine, Jon; Tomlinson, Jeremy W; Stewart, Paul M; Lavery, Gareth G

    2016-09-01

    Nonalcoholic fatty liver disease (NAFLD) defines a spectrum of conditions from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis and is regarded as the hepatic manifestation of the metabolic syndrome. Glucocorticoids can promote steatosis by stimulating lipolysis within adipose tissue, free fatty acid delivery to liver and hepatic de novo lipogenesis. Glucocorticoids can be reactivated in liver through 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme activity. Inhibition of 11β-HSD1 has been suggested as a potential treatment for NAFLD. To test this, male mice with global (11β-HSD1 knockout [KO]) and liver-specific (LKO) 11β-HSD1 loss of function were fed the American Lifestyle Induced Obesity Syndrome (ALIOS) diet, known to recapitulate the spectrum of NAFLD, and metabolic and liver phenotypes assessed. Body weight, muscle and adipose tissue masses, and parameters of glucose homeostasis showed that 11β-HSD1KO and LKO mice were not protected from systemic metabolic disease. Evaluation of hepatic histology, triglyceride content, and blinded NAFLD activity score assessment indicated that levels of steatosis were similar between 11β-HSD1KO, LKO, and control mice. Unexpectedly, histological analysis revealed significantly increased levels of immune foci present in livers of 11β-HSD1KO but not LKO or control mice, suggestive of a transition to NASH. This was endorsed by elevated hepatic expression of key immune cell and inflammatory markers. These data indicate that 11β-HSD1-deficient mice are not protected from metabolic disease or hepatosteatosis in the face of a NAFLD-inducing diet. However, global deficiency of 11β-HSD1 did increase markers of hepatic inflammation and suggests a critical role for 11β-HSD1 in restraining the transition to NASH.

  9. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis.

    PubMed

    Xiao, Guangqin; Zhu, Sixian; Xiao, Xiao; Yan, Lunan; Yang, Jiayin; Wu, Gang

    2017-11-01

    Many noninvasive methods for diagnosing liver fibrosis (LF) have been proposed. To determine the best method for diagnosing LF in nonalcoholic fatty liver disease (NAFLD), we conducted a systemic review and meta-analysis to compare the performance of aspartate aminotransferase to platelets ratio index (APRI), fibrosis-4 index (FIB-4), BARD score, NAFLD fibrosis score (NFS), FibroScan, shear wave elastography (SWE), and magnetic resonance elastography (MRE) for diagnosing LF in NAFLD. We compared the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUROC) of these noninvasive methods for detecting significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis. Heterogeneity was explored using meta-regression. Sixty-four articles with a total of 13,046 NAFLD subjects were included. The overall mean prevalence of SF, AF, and cirrhosis was 45.0%, 24.0%, and 9.4% in NAFLD patients, respectively. With an APRI threshold of 1.0 and 1.5, the sensitivities and specificities were 50.0% and 84.0% and 18.3% and 96.1%, respectively, for AF. With a FIB-4 threshold of 2.67 and 3.25, the sensitivities and specificities were 26.6% and 96.5% and 31.8% and 96.0%, respectively, for AF. The summary sensitivities and specificities of BARD score (threshold of 2), NFS (threshold of -1.455), FibroScan M (threshold of 8.7-9), SWE, and MRE for detecting AF were 0.76 and 0.61, 0.72 and 0.70, 0.87 and 0.79, 0.90 and 0.93, and 0.84 and 0.90, respectively. The summary AUROC values using APRI, FIB-4, BARD score, NFS, FibroScan M probe, XL probe, SWE, and MRE for diagnosing AF were 0.77, 0.84, 0.76, 0.84, 0.88, 0.85, 0.95, and 0.96, respectively. MRE and SWE may have the highest diagnostic accuracy for staging fibrosis in NAFLD patients. Among the four noninvasive simple indexes, NFS and FIB-4 probably offer the best diagnostic performance for detecting AF. (Hepatology 2017;66:1486-1501). © 2017 by the

  10. An examination of presenteeism measures: the association of three scoring methods with health, work life, and consumer activation.

    PubMed

    Terry, Paul E; Xi, Min

    2010-12-01

    The objective of this study was to assess the validity of 3 scoring techniques for presenteeism measures by exploring their relationship with patient activation, health, job satisfaction, and socioeconomic characteristics. The sample consisted of 631 employees from 2 predominantly white-collar employee groups in the northern Midwest. Employees completed the World Health Organization's Health and Work Performance Questionnaire, a wellness profile, and the Patient Activation Measure. Absolute measures reflect self-rated performance, while relative and stratified measures compare self-rated performance to that of co-workers. Multivariate analyses were used to validate scoring measures. All measures of presenteeism were positively correlated with being nonwhite, income, and smoking. The significance of age, employment, mental health, and patient activation depends on how presenteeism is defined. Practitioners must carefully consider which scoring method best addresses their program goals and objectives. Clearer measurement guidelines are needed.

  11. Do Genetic Markers of Inflammation Modify the Relationship between Periodontitis and Nonalcoholic Fatty Liver Disease? Findings from the SHIP Study.

    PubMed

    Akinkugbe, A A; Avery, C L; Barritt, A S; Cole, S R; Lerch, M; Mayerle, J; Offenbacher, S; Petersmann, A; Nauck, M; Völzke, H; Slade, G D; Heiss, G; Kocher, T; Holtfreter, B

    2017-11-01

    An association between periodontitis and nonalcoholic fatty liver disease (NAFLD) has been reported by experimental animal and epidemiologic studies. This study investigated whether circulating levels of serum C-reactive protein (CRP) and a weighted genetic CRP score representing markers of inflammatory burden modify the association between periodontitis and NAFLD. Data came from 2,481 participants of the Study of Health in Pomerania who attended baseline examination that occurred between 1997 and 2001. Periodontitis was defined as the percentage of sites (0%, <30%, ≥30%) with probing pocket depth (PD) ≥4 mm, and NAFLD status was determined using liver ultrasound assessment. Serum CRP levels were assayed at a central laboratory, and single-nucleotide polymorphisms previously identified through genome-wide association studies as robustly associated with serum CRP were combined into a weighted genetic CRP score (wGS CRP ). Logistic regression models estimated the association between periodontitis and NAFLD within strata of serum CRP and separately within strata of the wGS CRP . The prevalence of NAFLD was 26.4% (95% confidence interval [CI], 24.6, 28.1) while 17.8% (95% CI, 16.0-19.6) had ≥30% of sites with PD ≥4 mm. Whereas the wGS CRP was not a modifier ( P interaction = 0.8) on the multiplicative scale, serum CRP modified the relationship between periodontitis and NAFLD ( P interaction = 0.01). The covariate-adjusted prevalence odds ratio of NAFLD comparing participants with ≥30% of sites with PD ≥4 mm to those with no site affected was 2.39 (95% CI, 1.32-4.31) among participants with serum CRP <1 mg/L. The corresponding estimate was 0.97 (95% CI, 0.57-1.66) for participants with serum CRP levels of 1 to 3 mg/L and 1.12 (95% CI, 0.65-1.93) for participants with serum CRP >3 mg/L. Periodontitis was positively associated with higher prevalence odds of NAFLD, and this relationship was modified by serum CRP levels.

  12. Physical activity, stress, and metabolic risk score in 8- to 18-year-old boys.

    PubMed

    Holmes, Megan E; Eisenmann, Joey C; Ekkekakis, Panteleimon; Gentile, Douglas

    2008-03-01

    We examined whether physical activity modifies the relationship between stress and the metabolic risk score in 8- to 18-year-old males (n = 37). Physical activity (PA) and television (TV)/videogame (VG) use were assessed via accelerometer and questionnaire, respectively. Stress was determined from self-report measures. A metabolic risk score (MRS) was created by summing age-standardized residuals for waist circumference, mean arterial pressure, glycosylated hemoglobin, and high-density lipoprotein cholesterol. Correlations between PA and MRS were low (r < -.13), and TV and VG were moderately associated with MRS (r = .39 and .43, respectively). Correlations between stress-related variables and MRS ranged from r = .19 to .64. After partitioning by PA, significant correlations were observed in the low PA group between school- and sports-related self-esteem and anxiety with the MRS. The results provide suggestive evidence that PA might modify the relationship between stress and MRS in male adolescents.

  13. Pro-Inflammatory Activated Kupffer Cells by Lipids Induce Hepatic NKT Cells Deficiency through Activation-Induced Cell Death

    PubMed Central

    Tang, Tongfang; Sui, Yongheng; Lian, Min; Li, Zhiping; Hua, Jing

    2013-01-01

    Background Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response. Aims The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. Methods Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. Results High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. Conclusion High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD. PMID:24312613

  14. Clinical features and treatment of nonalcoholic fatty liver disease across the Asia Pacific region-the GO ASIA initiative.

    PubMed

    Chan, W-K; Treeprasertsuk, S; Imajo, K; Nakajima, A; Seki, Y; Kasama, K; Kakizaki, S; Fan, J-G; Song, M J; Yoon, S K; Dan, Y-Y; Lesmana, L; Ho, K-Y; Goh, K-L; Wong, V W-S

    2018-03-01

    The Gut and Obesity Asia (GO ASIA) workgroup was formed to study the relationships between obesity and gastrointestinal diseases in the Asia Pacific region. To study factors associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, and medical treatment of biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients. Retrospective study of biopsy-proven NAFLD patients from centres in the GO ASIA Workgroup. Independent factors associated with NASH and with advanced fibrosis on binary logistic regression analyses in a training cohort were used for the development of their corresponding risk score, which were validated in a validation cohort. We included 1008 patients from nine centres across eight countries (NASH 62.9%, advanced fibrosis 17.2%). Independent predictors of NASH were body mass index ≥30 kg/m 2 , diabetes mellitus, dyslipidaemia, alanine aminotransferase ≥88 U/L and aspartate aminotransferase ≥38 U/L, constituting the Asia Pacific NASH risk score. A high score has a positive predictive value of 80%-83% for NASH. Independent predictors of advanced fibrosis were age ≥55 years, diabetes mellitus and platelet count <150 × 10 9 /L, constituting the Asia-Pacific NAFLD advanced fibrosis risk score. A low score has a negative predictive value of 95%-96% for advanced fibrosis. Only 1.7% of patients were referred for structured lifestyle program, 4.2% were on vitamin E, and 2.4% were on pioglitazone. More severe liver disease can be suspected or ruled out based on factors identified in this study. Utilisation of structured lifestyle program, vitamin E and pioglitazone was limited despite this being a cohort of biopsy-proven NAFLD patients with majority of patients having NASH. © 2018 John Wiley & Sons Ltd.

  15. Potential Regulators Driving the Transition in Nonalcoholic Fatty Liver Disease: a Stage-Based View.

    PubMed

    Lou, Yi; Chen, Yi-Dan; Sun, Fu-Rong; Shi, Jun-Ping; Song, Yu; Yang, Jin

    2017-01-01

    The incidence of nonalcoholic fatty liver disease (NAFLD), ranging from mild steatosis to hepatocellular injury and inflammation, increases with the rise of obesity. However, the implications of transcription factors network in progressive NAFLD remain to be determined. A co-regulatory network approach by combining gene expression and transcription influence was utilized to dissect transcriptional regulators in different NAFLD stages. In vivo, mice models of NAFLD were used to investigate whether dysregulated expression be undertaken by transcriptional regulators. Through constructing a large-scale co-regulatory network, sample-specific regulator activity was estimated. The combinations of active regulators that drive the progression of NAFLD were identified. Next, top regulators in each stage of NAFLD were determined, and the results were validated using the different experiments and bariatric surgical samples. In particular, Adipocyte enhancer-binding protein 1 (AEBP1) showed increased transcription activity in nonalcoholic steatohepatitis (NASH). Further characterization of the AEBP1 related transcription program defined its co-regulators, targeted genes, and functional organization. The dynamics of AEBP1 and its potential targets were verified in an animal model of NAFLD. This study identifies putative functions for several transcription factors in the pathogenesis of NAFLD and may thus point to potential targets for therapeutic interventions. © 2017 The Author(s) Published by S. Karger AG, Basel.

  16. Design and rationale of the INSYTE study: A randomised, placebo controlled study to test the efficacy of a synbiotic on liver fat, disease biomarkers and intestinal microbiota in non-alcoholic fatty liver disease.

    PubMed

    Scorletti, Eleonora; Afolabi, Paul R; Miles, Elizabeth A; Smith, Debbie E; Almehmadi, Amal; Alshathry, Albandri; Moyses, Helen E; Clough, Geraldine F; Wright, Mark; Patel, Janisha; Bindels, Laure; Delzenne, Nathalie M; Calder, Philip C; Byrne, Christopher D

    2018-05-19

    Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the gut and liver are linked anatomically via the portal vein, disturbances of the gut microbiota (dysbiosis) can affect the liver. In patients with NAFLD, we are testing the effects of a synbiotic which is the combination of a prebiotic (fructooligosaccharides; 4 g/day) and a probiotic (Bifidobacterium animalis subsp. lactis BB-12 at a minimum of 10 billion CFU/day) on a) liver fat percentage, b) NAFLD fibrosis algorithm scores, c) gut microbiota composition. Additionally, there will be several hypothesis-generating secondary outcomes to understand the metaorganismal pathways that influence the development and progression of NAFLD, type 2 diabetes, and cardiovascular risk. In a randomised double-blind placebo controlled trial, 104 participants were randomised to 10-14 months intervention with either synbiotic (n = 55) or placebo (n = 49). Change in gut microbiota composition will be assessed using 16S ribosomal RNA gene sequencing. Change in mean liver fat percentage will be quantified by magnetic resonance spectroscopy (MRS). In addition, change in liver fat severity will be measured using two NAFLD fibrosis algorithm scores. Recruitment was completed in April 2017 and the last study visit will be completed by April 2018. The INSYTE study was approved by the local ethics committee (REC: 12/SC/0614) and is registered at www.clinicaltrials.gov as NCT01680640. Copyright © 2017. Published by Elsevier Inc.

  17. Twitter Activity Associated With U.S. News and World Report Reputation Scores for Urology Departments.

    PubMed

    Ciprut, Shannon; Curnyn, Caitlin; Davuluri, Meena; Sternberg, Kevan; Loeb, Stacy

    2017-10-01

    To analyze the association between US urology department Twitter presence and U.S. News and World Report (USNWR) reputation scores, to examine the content, informational value, and intended audience of these platforms, and to identify objectives for Twitter use. We identified Twitter accounts for urology departments scored in the 2016-2017 USNWR. Correlation coefficients were calculated between Twitter metrics (number of followers, following, tweets, and Klout influence scores) with USNWR reputation scores. We also performed a detailed content analysis of urology department tweets during a 6-month period to characterize the content. Finally, we distributed a survey to the urology department accounts via Twitter, inquiring who administers the content, and their objectives for Twitter use. Among 42 scored urology departments with Twitter accounts, the median number of followers, following, and tweets were 337, 193, and 115, respectively. All of these Twitter metrics had a statistically significant positive correlation with reputation scores (P <.05). Content analyses revealed that most tweets were about conferences, education, and publications, targeting the general public or urologic community. Survey results revealed that the primary reason for twitter use among urology departments was visibility and reputation, and urologists are considered the most important target audience. There is statistically significant correlation between Twitter activity and USNWR reputation scores for urology departments. Our results suggest that Twitter provides a novel mechanism for urology departments to communicate about academic and educational topics, and social media engagement can enhance reputation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations

    PubMed Central

    Nelson, James E.; Brunt, Elizabeth M.; Kowdley, Kris V.

    2012-01-01

    Hepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic iron deposition and histology in nonalcoholic fatty liver disease (NAFLD). SNP genotyping for C282Y (rs1800562) and H63D (rs1799945) HFE mutations was performed in 786 adult subjects in the NASH Clinical Research Network (CRN). Clinical, histologic, and laboratory data were compared using nonparametric statistics and multivariate logistic regression. NAFLD patients with C282Y, but not H63D mutations, had lower median serum hepcidin levels (57 vs 65 ng/ml, p=0.01) and higher mean hepatocellular (HC) iron grades (0.59 vs 0.28, p<0.001), compared to wild type (WT) subjects. Subjects with hepatic iron deposition had higher serum hepcidin levels than subjects without iron for all HFE genotypes (p<0.0001). Hepcidin levels were highest among patients with mixed HC/reticuloendothelial system cell (RES) iron deposition. H63D mutations were associated with higher steatosis grades and NAFLD activity scores (OR≥1.4, CI >1.0≤2.5, p≤0.041), compared to WT, but not with either HC or RES iron. NAFLD patients with C282Y mutations had less ballooning or NASH (OR ≤0.62, 95% CI >0.39<0.94, p≤0.024) compared to WT subjects. Conclusions Presence of C282Y mutations in patients with NAFLD is associated with greater HC iron deposition and decreased serum hepcidin levels and there is a positive relationship between hepatic iron stores and serum hepcidin level across all HFE genotypes. These data suggest that body iron stores are the major determinant of hepcidin regulation in NAFLD regardless of HFE genotype. A potential role for H63D mutations in NAFLD pathogenesis is possible through iron-independent mechanisms. PMID:22611049

  19. Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations.

    PubMed

    Nelson, James E; Brunt, Elizabeth M; Kowdley, Kris V

    2012-11-01

    Hepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic iron deposition, and histology in nonalcoholic fatty liver disease (NAFLD). Single-nucleotide polymorphism genotyping for C282Y (rs1800562) and H63D (rs1799945) HFE mutations was performed in 786 adult subjects in the NASH Clinical Research Network (CRN). Clinical, histologic, and laboratory data were compared using nonparametric statistics and multivariate logistic regression. NAFLD patients with C282Y, but not H63D mutations, had lower median serum hepcidin levels (57 versus 65 ng/mL; P = 0.01) and higher mean hepatocellular (HC) iron grades (0.59 versus 0.28; P < 0.001), compared to wild-type (WT) subjects. Subjects with hepatic iron deposition had higher serum hepcidin levels than subjects without iron for all HFE genotypes (P < 0.0001). Hepcidin levels were highest among patients with mixed HC/reticuloendothelial system cell (RES) iron deposition. H63D mutations were associated with higher steatosis grades and NAFLD activity scores (odds ratio [OR], ≥1.4; 95% confidence interval [CI]: >1.0, ≤2.5; P ≤ 0.041), compared to WT, but not with either HC or RES iron. NAFLD patients with C282Y mutations had less ballooning or NASH (OR, ≤0.62; 95% CI: >0.39, <0.94; P ≤ 0.024), compared to WT subjects. The presence of C282Y mutations in patients with NAFLD is associated with greater HC iron deposition and decreased serum hepcidin levels, and there is a positive relationship between hepatic iron stores and serum hepcidin level across all HFE genotypes. These data suggest that body iron stores are the major determinant of hepcidin regulation in NAFLD, regardless of HFE genotype. A potential role for H63D mutations in NAFLD pathogenesis is possible through iron-independent mechanisms. Copyright © 2012 American Association

  20. Nimesulide, a cyclooxygenase-2 selective inhibitor, suppresses obesity-related non-alcoholic fatty liver disease and hepatic insulin resistance through the regulation of peroxisome proliferator-activated receptor γ

    PubMed Central

    Tsujimoto, Shunsuke; Kishina, Manabu; Koda, Masahiko; Yamamoto, Yasutaka; Tanaka, Kohei; Harada, Yusuke; Yoshida, Akio; Hisatome, Ichiro

    2016-01-01

    Cyclooxygenase (COX)-2 selective inhibitors suppress non-alcoholic fatty liver disease (NAFLD); however, the precise mechanism of action remains unknown. The aim of this study was to examine how the COX-2 selective inhibitor nimesulide suppresses NAFLD in a murine model of high-fat diet (HFD)-induced obesity. Mice were fed either a normal chow diet (NC), an HFD, or HFD plus nimesulide (HFD-nime) for 12 weeks. Body weight, hepatic COX-2 mRNA expression and triglyceride accumulation were significantly increased in the HFD group. Triglyceride accumulation was suppressed in the HFD-nime group. The mRNA expression of hepatic peroxisome proliferator-activated receptor γ (PPARγ) and the natural PPARγ agonist 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) were significantly increased in the HFD group and significantly suppressed in the HFD-nime group. Glucose metabolism was impaired in the HFD group compared with the NC group, and it was significantly improved in the HFD-nime group. In addition, the plasma insulin levels in the HFD group were increased compared with those in the NC group, and were decreased in the HFD-nime group. These results indicate that HFD-induced NAFLD is mediated by the increased hepatic expression of COX-2. We suggest that the production of 15d-PGJ2, which is mediated by COX-2, induces NAFLD and hepatic insulin resistance by activating PPARγ. Furthermore, the mRNA expression of tissue inhibitor of metalloproteinases-1 (TIMP-1), procollagen-1 and monocyte chemoattractant protein-1 (MCP-1), as well as the number of F4/80-positive hepatic (Kupffer) cells, were significantly increased in the HFD group compared with the NC group, and they were reduced by nimesulide. In conclusion, COX-2 may emerge as a molecular target for preventing the development of NAFLD and insulin resistance in diet-related obesity. PMID:27431935

  1. Analytical, anthropometric and dietary factors associated with the development of fibrosis in patients with nonalcoholic fatty liver disease.

    PubMed

    Gómez de la Cuesta, Sara; Aller de la Fuente, Rocío; Tafur Sánchez, Carla; Izaola, Olatz; García Sánchez, Concepción; Mora, Natalia; González Hernández, Jose Manuel; de Luis Román, Daniel

    2018-05-01

    a prolonged non-alcoholic steatohepatitis (NASH) condition can lead to advanced stages of liver disease and the development of hepatocellular carcinoma. to evaluate analytical, anthropometric and dietary factors associated with the presence of fibrosis as this is the factor that most influences survival and evolution. seventy-six patients with liver biopsy-diagnosed non-alcoholic fatty liver disease (NAFLD) were included. Biopsies were scored considering the NASH criteria of Kleiner. Analytical, anthropometric and dietary (survey) parameters were obtained. NAFLD-FS is a non-invasive fibrosis index and was assessed for each patient. Leptin, adiponectin, resistin and TNF-alpha serum levels were determined. fifty-six patients were male (73.7%) and the mean age was 44.5 ± 11.3 years of age (19-68). Thirty-nine (51.3%) (F1-F2: 84.6%; F3-4: 15.4%) patients had fibrosis in the liver biopsy. Seventeen females (85%) had fibrosis versus 22 males (39%), which was statistically significant by univariate analysis (p < 0.01). Patients with advanced fibrosis were older, with lower platelet counts, lower serum albumin, greater homeostatic model assessment insulin resistance (HOMA-IR), lower dietary lipids percentage, higher serum leptin levels and higher NAFLD Fibrosis Score (NAFLD-FS) values. This index had a negative predictive value of 98% and a positive predictive value of 60% for the detection of fibrosis. Variables independently associated with fibrosis (logistic regression) included male gender (protective factor) (0.09, 95% CI 0.01-0.7; p < 0.05) and HOMA-IR (1.7, 95% CI, 1.03-2.79; p < 0.05). gender and HOMA-IR were the only independent factors associated with fibrosis. NAFLD-FS could be considered as an accurate scoring system to rule out advanced fibrosis.

  2. Suboptimal performance of simple noninvasive tests for advanced fibrosis in Chinese patients with nonalcoholic fatty liver disease.

    PubMed

    Xun, Yun Hao; Fan, Jian Gao; Zang, Guo Qing; Liu, Hong; Jiang, Yan Ming; Xiang, Jing; Huang, Qian; Shi, Jun Ping

    2012-11-01

    To evaluate the diagnostic accuracy of some noninvasive fibrosis models in Chinese patients with nonalcoholic fatty liver disease (NAFLD). Consecutive biopsy-proven NAFLD patients were recruited from a single center from January 2005 to December 2010. Advanced fibrosis (stage 3 and 4) was defined using Kleiner criteria. The area under the receiver operating characteristic curve (AUROC) was used to compare the diagnostic accuracy of the NAFLD fibrosis score (NFS), FIB-4 index, aspartate transaminase (AST)/platelet ratio index (APRI), AST/alanine transaminase (ALT) ratio (AAR) and body mass index (BMI)-AAR-Diabetes (BARD) score. Of the patients with NAFLD, 79.6% were males with a mean age of 37.1 years, mean BMI of 26.1 kg/m(2) and 41.4% of them had nonalcoholic steatohepatitis, and 24 (15.8%) had advanced fibrosis. The AUROC of the FIB-4 index, APRI, AAR, NFS and BARD score for advanced fibrosis were 0.756, 0.742, 0.670, 0.653 and 0.642 (P < 0.05 for all), respectively. A concordant negative predictive value of approximately 90% was indicated whereas the positive predictive values were modest for all tests, and only the FIB-4 index yielded a higher positive likelihood ratio of 7.65. Using these cut-off values of tests for excluding advanced fibrosis could reduce the use of liver biopsy in 56.6-74.3% of the patients, with a minor false negative rate of 5.3-9.9%. Although slightly less accurate than liver biopsy, simple noninvasive tests can reliably exclude advanced fibrosis in Chinese NAFLD patients in our center. FIB-4 index performs better than the other tests under examination. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  3. Walk Score®

    PubMed Central

    Brown, Scott C.; Pantin, Hilda; Lombard, Joanna; Toro, Matthew; Huang, Shi; Plater-Zyberk, Elizabeth; Perrino, Tatiana; Perez-Gomez, Gianna; Barrera-Allen, Lloyd; Szapocznik, José

    2013-01-01

    Background Walk Score® is a nationally and publicly available metric of neighborhood walkability based on proximity to amenities (e.g., retail, food, schools). However, few studies have examined the relationship of Walk Score to walking behavior. Purpose To examine the relationship of Walk Score to walking behavior in a sample of recent Cuban immigrants, who overwhelmingly report little choice in their selection of neighborhood built environments when they arrive in the U.S. Methods Participants were 391 recent healthy Cuban immigrants (M age=37.1 years) recruited within 90 days of arrival in the U.S., and assessed within 4 months of arrival (M=41.0 days in the U.S.), who resided throughout Miami-Dade County FL. Data on participants’ addresses, walking and sociodemographics were collected prospectively from 2008 to 2010. Analyses conducted in 2011 examined the relationship of Walk Score for each participant’s residential address in the U.S. to purposive walking, controlling for age, gender, education, BMI, days in the U.S., and habitual physical activity level in Cuba. Results For each 10-point increase in Walk Score, adjusting for covariates, there was a significant 19% increase in the likelihood of purposive walking, a 26% increase in the likelihood of meeting physical activity recommendations by walking, and 27% more minutes walked in the previous week. Conclusions Results suggest that Walk Score is associated with walking in a sample of recent immigrants who initially had little choice in where they lived in the U.S. These results support existing guidelines indicating that mixed land use (such as parks and restaurants near homes) should be included when designing walkable communities. PMID:23867028

  4. The Pancreatitis Activity Scoring System predicts clinical outcomes in acute pancreatitis: findings from a prospective cohort study.

    PubMed

    Buxbaum, James; Quezada, Michael; Chong, Bradford; Gupta, Nikhil; Yu, Chung Yao; Lane, Christianne; Da, Ben; Leung, Kenneth; Shulman, Ira; Pandol, Stephen; Wu, Bechien

    2018-05-01

    The Pancreatitis Activity Scoring System (PASS) has been derived by an international group of experts via a modified Delphi process. Our aim was to perform an external validation study to assess for concordance of the PASS score with high face validity clinical outcomes and determine specific meaningful thresholds to assist in application of this scoring system in a large prospectively ascertained cohort. We analyzed data from a prospective cohort study of consecutive patients admitted to the Los Angeles County Hospital between March 2015 and March 2017. Patients were identified using an emergency department paging system and electronic alert system. Comprehensive characterization included substance use history, pancreatitis etiology, biochemical profile, and detailed clinical course. We calculated the PASS score at admission, discharge, and at 12 h increments during the hospitalization. We performed several analyses to assess the relationship between the PASS score and outcomes at various points during hospitalization as well as following discharge. Using multivariable logistic regression analysis, we assessed the relationship between admission PASS score and risk of severe pancreatitis. PASS score performance was compared to established systems used to predict severe pancreatitis. Additional inpatient outcomes assessed included local complications, length of stay, development of systemic inflammatory response syndrome (SIRS), and intensive care unit (ICU) admission. We also assessed whether the PASS score at discharge was associated with early readmission (re-hospitalization for pancreatitis symptoms and complications within 30 days of discharge). A total of 439 patients were enrolled, their mean age was 42 (±15) years, and 53% were male. Admission PASS score >140 was associated with moderately severe and severe pancreatitis (OR 3.5 [95% CI 2.0, 6.3]), ICU admission (OR 4.9 [2.5, 9.4]), local complications (3.0 [1.6, 5.7]), and development of SIRS (OR 2.9 [1

  5. Pilot study of the prevalence of binge eating disorder in non-alcoholic fatty liver disease patients.

    PubMed

    Zhang, Jinyu; Abbasi, Omair; Malevanchik, Lev; Mohan, Neena; Denicola, Richard; Tarangelo, Nicholas; Marzio, Dina Halegoua-De

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States. Binge eating disorder (BED) is the most common form of eating disorder. NAFLD and BED have similar risk factors, including obesity, insulin resistance, and metabolic syndrome. The aim of our study was to examine prevalence of BED in NAFLD patients. We administered the Binge Eating Scale (BES), a questionnaire validated to screen for BED, to NAFLD patients at our Fatty Liver Center. Demographics were retrieved retrospectively from our electronic medical record. Of the total 95 NAFLD patients screened, 22 (23.1%) had binge eating tendencies; 6 of the 22 (6.3%) scored 27 or more points, suggestive of severe binge eating. Patient demographics included 59 females and 36 males (14 females and 8 males positive for BED). Liver disease severity and of metabolic syndrome presence were similar in both groups: 45 patients had steatosis, 25 steatohepatitis, and 24 cirrhosis, of which 10 steatosis, 5 steatohepatitis, and 7 cirrhosis patients screened positive for BED. Of the NAFLD patients with BED, 50.0% had insulin resistance, 68.2% hypertension, and 50.0% hyperlipidemia, whereas among non-BED NAFLD patients 58.9% had insulin resistance, 63.0% hypertension, and 67.1% hyperlipidemia. This pilot study suggests that BED may have a higher prevalence among NAFLD patients than in the general population. Based on these preliminary results, further study into the prevalence of BED is recommended. More data is need to identify effects of BED on the progression of NAFLD and role of BED treatment.

  6. Validation of the nursing workload scoring systems "Nursing Activities Score" (NAS), and "Therapeutic Intervention Scoring System For Critically Ill Children" (TISS-C) in a Greek Paediatric Intensive Care Unit.

    PubMed

    Nieri, Alexandra-Stavroula; Manousaki, Kalliopi; Kalafati, Maria; Padilha, Katia Grilio; Stafseth, Siv K; Katsoulas, Theodoros; Matziou, Vasiliki; Giannakopoulou, Margarita

    2018-04-11

    To assess the reliability and validity of the Greek version of Nursing Activities Score (NAS), and Therapeutic Intervention Scoring System for Critically Ill Children (TISS-C) in a Greek Paediatric Intensive Care Unit (PICU). A methodological study was performed in one PICU of the largest Paediatric Hospital in Athens-Greece. The culturally adapted and validated Greek NAS version, enriched according to the Norwegian paediatric one (P-NAS), was used. TISS-C and Norwegian paediatric interventions were translated to Greek language and backwards. Therapeutic Intervention Scoring System (TISS-28) was used as a gold standard. Two independent observers simultaneously recorded 30 daily P-NAS and TISS-C records. Totally, 188 daily P-NAS, TISS-C and TISS-28 reports in a sample of 29 patients have been obtained during 5 weeks. Descriptive statistics, reliability and validity measures were applied using SPSS (ver 22.0) (p ≤ 0.05). Kappa was 0.963 for P-NAS and 0.9895 for TISS-C (p < 0.001) and Intraclass Correlation Coefficient for all scale items of TISS-C was 1.00 (p < 0.001). P-NAS, TISS-28 and TISS-C measurements were significantly correlated (0.680 ≤ rho ≤ 0.743, p < 0.001). The mean score(±SD) for TISS-28, P-NAS and TISS-C was 23.05(±5.72), 58.14(±13.98) and 20.21(±9.66) respectively. These results support the validity of P-NAS and TISS-C scales to be used in Greek PICUs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

    PubMed Central

    Zhang, Xian; Zhang, Jian-Hua; Chen, Xu-Yang; Hu, Qing-Hua; Wang, Ming-Xing; Jin, Rui; Zhang, Qing-Yu; Wang, Wei; Wang, Rong; Kang, Lin-Lin; Li, Jin-Sheng; Li, Meng

    2015-01-01

    Abstract Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant

  8. Variation in dietary intake and physical activity pattern as predictors of change in body mass index (BMI) Z-score among Brazilian adolescents.

    PubMed

    Enes, Carla C; Slater, Betzabeth

    2013-06-01

    To assess whether changes in dietary intake and physical activity pattern are associated with the annual body mass index (BMI) z-score change among adolescents. The study was conducted in public schools in the city of Piracicaba, Sao Paulo, Brazil, with a probabilistic sample of 431 adolescents participating in wave I (2004) (hereafter, baseline) and 299 in wave II (2005) (hereafter, follow-up). BMI, usual food intake, physical activity, screen time, sexual maturation and demographic variables were assessed twice. The association between annual change in food intake, physical activity, screen time, and annual BMI z-score changes were assessed by multiple regression. The study showed a positive variation in BMI z-score over one-year. Among variables related to physical activity pattern only playing videogame and using computer increased over the year. The intake of fruits and vegetables and sugar-sweetened beverages increased over one year, while the others variables showed a reduction. An increased consumption of fatty foods (β = 0.04, p = 0.04) and sweetened natural fruit juices (β = 0.05, p = 0.03) was positively associated with the rise in BMI z-score. Unhealthy dietary habits can predict the BMI z-score gain more than the physical activity pattern. The intake of fatty foods and sweetened fruit juices is associated with the BMI z-score over one year.

  9. Diffusion-weighted imaging for evaluating inflammatory activity in Crohn's disease: comparison with histopathology, conventional MRI activity scores, and faecal calprotectin.

    PubMed

    Pendsé, D A; Makanyanga, J C; Plumb, A A; Bhatnagar, G; Atkinson, D; Rodriguez-Justo, Manuel; Halligan, S; Taylor, S A

    2017-01-01

    To evaluate whether the extent of enteric diffusion-weighted imaging (DWI) signal abnormality reflects inflammatory burden in Crohn's disease (CD), and to compare qualitative and quantitative grading. 69 CD patients (35 male, age 16-78) undergoing MR enterography with DWI (MRE-D) and the same-day faecal calprotectin (cohort 1) were supplemented by 29 patients (19 male, age 16-70) undergoing MRE-D and terminal ileal biopsy (cohort 2). Global (cohort 1) and terminal ileal (cohort 2) DWI signal was graded (0 to 3) by 2 radiologists and segmental apparent diffusion coefficient (ADC) calculated. Data were compared to calprotectin and a validated MRI activity score [MEGS] (cohort 1), and a histopathological activity score (eAIS) (cohort 2) using nonparametric testing and rank correlation. Patients with normal (grades 0 and 1) DWI signal had lower calprotectin and MEGS than those with abnormal signal (grades 2 and 3) (160 vs. 492 μg/l, p = 0.0004, and 3.3 vs. 21, p < 0.0001), respectively. Calprotectin was lower if abnormal DWI affected <10 cm of small bowel compared to diffuse small and large bowel abnormality (236 vs. 571 μg, p = 0.009). The sensitivity and specificity for active disease (calprotectin > 120 μg/l) were 83% and 52%, respectively. There was a negative correlation between ileal MEGS and ADC (r = -0.41, p = 0.017). There was no significant difference in eAIS between qualitative DWI scores (p = 0.42). Mean ADC was not different in those with and without histological inflammation (2077 vs. 1622 × 10 -6 mm 2 /s, p = 0.10) CONCLUSIONS: Qualitative grading of DWI signal has utility in defining the burden of CD activity. Quantitative ADC measurements have poor discriminatory ability for segmental disease activity.

  10. Low Birthweight Increases the Likelihood of Severe Steatosis in Pediatric Non-Alcoholic Fatty Liver Disease.

    PubMed

    Bugianesi, Elisabetta; Bizzarri, Carla; Rosso, Chiara; Mosca, Antonella; Panera, Nadia; Veraldi, Silvio; Dotta, Andrea; Giannone, Germana; Raponi, Massimiliano; Cappa, Marco; Alisi, Anna; Nobili, Valerio

    2017-08-01

    Small for gestational age (SGA) is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). Our aim was to investigate the correlation of birthweight with the severity of liver damage in a large cohort of children with NAFLD. Two hundred and eighty-eight consecutive Caucasian Italian overweight/obese children with biopsy-proven NAFLD were included in the study. We examined the relative association of each histological feature of NAFLD with metabolic alterations, insulin-resistance, I148M polymorphism in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, and birthweight relative to gestational age. In the whole NAFLD cohort, 12.2% of patients were SGA, 62.8% appropriate for gestational age (AGA), and 25% large for gestational age (LGA). SGA children had a higher prevalence of severe steatosis (69%) and severe portal inflammation (14%) compared with the AGA and LGA groups. Notably, severe steatosis (>66%) was decreasing from SGA to AGA and LGA, whereas the prevalence of moderate steatosis (33-66%) was similar in three groups. The prevalence of type 1 NAFLD is higher in the LGA group with respect to the other two groups (25% vs.5.2% vs.9.4%), whereas the SGA group shows a higher prevalence of overlap type (85.8%) with respect to the LGA group (51.4%) but not compared with the AGA group (75%). At multivariable regression analysis, SGA at birth increased fourfold the likelihood of severe steatosis (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.43-10.9, P=0.008) and threefold the likelihood of NAFLD Activity Score (NAS)≥5 (OR 2.98, 95% CI 1.06-8.33, P=0.037) independently of homeostasis model assessment of insulin resistance and PNPLA3 genotype. The PNPLA3-CC wild-type genotype was the strongest independent predictor of the absence of significant fibrosis (OR 0.26, 95% CI 0.13-0.52, P=<0.001). In children with NAFLD, the risk of severe steatosis is increased by SGA at birth, independent of and in addition to other

  11. Assessment of a neonatal unit nursing staff: application of the Nursing Activities Score.

    PubMed

    Nunes, Bruna Kosar; Toma, Edi

    2013-02-01

    The study proposes to analyze the nursing staff workload of the sectors of a neonatal unit by means of the Nursing Activities Score - NAS and to calculate the quantitative ideal for the team, comparing it with the current workload. The NAS tool was applied for all newborns interned for at least 24 hours; the sum of the NAS points provided the unit workload which was used for calculating the team assessment by means of mathematical equation. The sector of Low Risk presented a workload of 267 NAS points and an imbalance of 8.8 professionals daily; the Medium Risk sector a workload of 446.7 and an imbalance of 22.3; the High Risk sector a workload of 359 and a deficit of 17.9; the Isolation sector a demand of 609 and an imbalance of 18.2; and NICU a workload of 568.6 with a deficit of 16.1 professionals. The study disclosed an important imbalance of professionals in relation to the exalted work demand they are subjected to daily. The application of the Nursing Activities Score in neonatal units contributes to the evaluation of the workload and assessment of the nursing team.

  12. The Combined Intervention with Germinated Vigna radiata and Aerobic Interval Training Protocol Is an Effective Strategy for the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) and Other Alterations Related to the Metabolic Syndrome in Zucker Rats.

    PubMed

    Kapravelou, Garyfallia; Martínez, Rosario; Nebot, Elena; López-Jurado, María; Aranda, Pilar; Arrebola, Francisco; Cantarero, Samuel; Galisteo, Milagros; Porres, Jesus M

    2017-07-19

    Metabolic syndrome (MetS) is a group of related metabolic alterations that increase the risk of developing non-alcoholic fatty liver disease (NAFLD). Several lifestyle interventions based on dietary treatment with functional ingredients and physical activity are being studied as alternative or reinforcement treatments to the pharmacological ones actually in use. In the present experiment, the combined treatment with mung bean ( Vigna radiata ), a widely used legume with promising nutritional and health benefits that was included in the experimental diet as raw or 4 day-germinated seed flour, and aerobic interval training protocol (65-85% VO₂ max) has been tested in lean and obese Zucker rats following a 2 × 2 × 2 (2 phenotypes, 2 dietary interventions, 2 lifestyles) factorial ANOVA (Analysis of Variance) statistical analysis. Germination of V. radiata over a period of four days originated a significant protein hydrolysis leading to the appearance of low molecular weight peptides. The combination of 4 day-germinated V. radiata and aerobic interval training was more efficient compared to raw V. radiata at improving the aerobic capacity and physical performance, hepatic histology and functionality, and plasma lipid parameters as well as reverting the insulin resistance characteristic of the obese Zucker rat model. In conclusion, the joint intervention with legume sprouts and aerobic interval training protocol is an efficient treatment to improve the alterations of glucose and lipid metabolism as well as hepatic histology and functionality related to the development of NAFLD and the MetS.

  13. Involvement of AMP-activated protein kinase in beneficial effects of betaine on high-sucrose diet-induced hepatic steatosis

    PubMed Central

    Song, Zhenyuan; Deaciuc, Ion; Zhou, Zhanxiang; Song, Ming; Chen, Theresa; Hill, Daniell; McClain, Craig J.

    2014-01-01

    Although simple steatosis was originally thought to be a pathologically inert histological change, fat accumulation in the liver may play a critical role not only in disease initiation, but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Therefore, prevention of fat accumulation in the liver may be an effective therapy for multiple stages of nonalcoholic fatty liver disease (NAFLD). Promising beneficial effects of betaine supplementation on human NAFLD have been reported in some pilot clinical studies; however, data related to betaine therapy in NAFLD are limited. In this study, we examined the effects of betaine on fat accumulation in the liver induced by high-sucrose diet and evaluated mechanisms by which betaine could attenuate or prevent hepatic steatosis in this model. Male C57BL/6 mice weighing 20 ± 0.5 g (means ± SE) were divided into four groups (8 mice per group) and started on one of four treatments: standard diet (SD), SD+betaine, high-sucrose diet (HS), and HS + betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Long-term feeding of high-sucrose diet to mice caused significant hepatic steatosis accompanied by markedly increased lipogenic activity. Betaine significantly attenuated hepatic steatosis in this animal model, and this change was associated with increased activation of hepatic AMP-activated protein kinase (AMPK) and attenuated lipogenic capability (enzyme activities and gene expression) in the liver. Our findings are the first to suggest that betaine might serve as a therapeutic tool to attenuate hepatic steatosis by targeting the hepatic AMPK system. PMID:17702954

  14. A genetic risk score is associated with hepatic triglyceride content and non-alcoholic steatohepatitis in Mexicans with morbid obesity.

    PubMed

    León-Mimila, Paola; Vega-Badillo, Joel; Gutiérrez-Vidal, Roxana; Villamil-Ramírez, Hugo; Villareal-Molina, Teresa; Larrieta-Carrasco, Elena; López-Contreras, Blanca E; Kauffer, Luis R Macías; Maldonado-Pintado, Diana G; Méndez-Sánchez, Nahúm; Tovar, Armando R; Hernández-Pando, Rogelio; Velázquez-Cruz, Rafael; Campos-Pérez, Francisco; Aguilar-Salinas, Carlos A; Canizales-Quinteros, Samuel

    2015-04-01

    Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near/in PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes associated with non-alcoholic fatty liver disease (NAFLD) mainly in individuals of European ancestry. The aim of the study was to test whether these genetic variants and a genetic risk score (GRS) are associated with elevated liver fat content and non-alcoholic steatohepatitis (NASH) in Mexicans with morbid obesity. 130 morbidly obese Mexican individuals were genotyped for six SNPs in/near PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes. Hepatic fat content [triglyceride (HTG) and total cholesterol (HTC)] was quantified directly in liver biopsies and NASH was diagnosed by histology. A GRS was tested for association with liver fat content and NASH using logistic regression models. In addition, 95 ancestry-informative markers were genotyped to estimate population admixture proportions. After adjusting for age, sex and admixture, PNPLA3, LYPLAL1, GCKR and PPP1R3B polymorphisms were associated with higher HTG content (P < 0.05 for PNPLA3, LYPLAL1, GCKR polymorphisms and P = 0.086 for PPP1R3B). The GRS was significantly associated with higher HTG and HTC content (P = 1.0 × 10(-4) and 0.048, respectively), steatosis stage (P = 0.029), and higher ALT levels (P = 0.002). Subjects with GRS ≥ 6 showed a significantly increased risk of NASH (OR = 2.55, P = 0.045) compared to those with GRS ≤ 5. However, the GRS did not predict NASH status, as AUC of ROC curves was 0.56 (P = 0.219). NAFLD associated loci in Europeans and a GRS based on these loci contribute to the accumulation of hepatic lipids and NASH in morbidly obese Mexican individuals. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Activation of hepatic Nogo-B receptor expression—A new anti-liver steatosis mechanism of statins

    PubMed Central

    Zhang, Wenwen; Yang, Xiaoxiao; Chen, Yuanli; Hu, Wenquan; Liu, Lipei; Zhang, Xiaomeng; Liu, Mengyang; Sun, Lei; Liu, Ying; Yu, Miao; Li, Xiaoju; Li, Luyuan; Zhu, Yan; Miao, Qing Robert; Han, Jihong; Duan, Yajun

    2017-01-01

    Deficiency of hepatic Nogo-B receptor (NgBR) expression activates liver X receptor α (LXRα) in an adenosine monophosphate-activated protein kinase α (AMPKα)-dependent manner, thereby inducing severe hepatic lipid accumulation and hypertriglyceridemia. Statins have been demonstrated non-cholesterol lowering effects including anti-nonalcoholic fatty liver disease (NAFLD). Herein, we investigated if the anti-NAFLD function of statins depends on activation of NgBR expression. In vivo, atorvastatin protected apoE deficient or NgBR floxed, but not hepatic NgBR deficient mice, against Western diet (WD)-increased triglyceride levels in liver and serum. In vitro, statins reduced lipid accumulation in nonsilencing small hairpin RNA-transfected (shNSi), but not in NgBR small hairpin RNA-transfected (shNgBRi) HepG2 cells. Inhibition of cellular lipid accumulation by atorvastatin is related to activation of AMPKα, and inactivation of LXRα and lipogenic genes. Statin also inhibited expression of oxysterol producing enzymes. Associated with changes of hepatic lipid levels by WD or atorvastatin, NgBR expression was inversely regulated. At cellular levels, statins increased NgBR mRNA and protein expression, and NgBR protein stability. In contrast to reduced cellular cholesterol levels by statin or β-cyclodextrin, increased cellular cholesterol levels decreased NgBR expression suggesting cholesterol or its synthesis intermediates inhibit NgBR expression. Indeed, mevalonate, geranylgeraniol or geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate or farnesol, blocked atorvastatin-induced NgBR expression. Furthermore, we determined that induction of hepatic NgBR expression by atorvastatin mainly depended on inactivation of extracellular signal-regulated kinases 1/2 (ERK1/2) and protein kinase B (Akt). Taken together, our study demonstrates that statins inhibit NAFLD mainly through activation of NgBR expression. PMID:29217477

  16. Alimentary habits, physical activity, and Framingham global risk score in metabolic syndrome.

    PubMed

    Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo

    2014-04-01

    Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p < 0.001). We obtained a reduction for intermediate risk in 25.7% of subjects. After intervention, there was a significant reduction (p < 0.01) on cardiovascular age, this being more significant in groups DIP (5.2%) and DIPE (5.3%). Proposed interventions produced beneficial effects for reducing cardiovascular risk score. This study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases.

  17. Genistein Ameliorates Non-alcoholic Fatty Liver Disease by Targeting the Thromboxane A2 Pathway.

    PubMed

    Wang, Wenzhe; Chen, Junliang; Mao, Jinyan; Li, Hongling; Wang, Mingfu; Zhang, Hao; Li, Haitao; Chen, Wei

    2018-06-13

    Non-alcoholic fatty liver disease (NAFLD) is now a public health issue worldwide, but no drug has yet received approval. Genistein, an isoflavonoid derived from soybean, ameliorates high-fat-diet-induced NAFLD in mice, but the molecular underpinnings remain largely elusive. Arachidonic acid (AA) is a major ingredient of animal fats, and the AA cascade has been implicated in chronic inflammation. In this study, we investigated whether genistein was against NAFLD by targeting the AA cascade. Using a mouse model, we showed that genistein supplementation improved high-fat-diet-induced NAFLD by normalizing hepatomegaly, liver steatosis, aminotransferase abnormalities, and glucose tolerance. The thromboxane A 2 (TXA 2 ) pathway was aberrantly active in NAFLD, evidenced by an elevation of circulating TXA 2 and hepatic thromboxane A 2 receptor expression. Mechanistically, we found that genistein directly targeted cyclooxygenase-1 activity as well as its downstream TXA 2 biosynthesis, while the TXA 2 pathway might mediate NAFLD progression by impairing insulin sensitivity. Taken together, our study revealed a crucial pathophysiological role of the TXA 2 pathway in NAFLD and provided an explanation as to how genistein was against NAFLD progression.

  18. Mathematical Justification of Expression-Based Pathway Activation Scoring (PAS).

    PubMed

    Aliper, Alexander M; Korzinkin, Michael B; Kuzmina, Natalia B; Zenin, Alexander A; Venkova, Larisa S; Smirnov, Philip Yu; Zhavoronkov, Alex A; Buzdin, Anton A; Borisov, Nikolay M

    2017-01-01

    Although modeling of activation kinetics for various cell signaling pathways has reached a high grade of sophistication and thoroughness, most such kinetic models still remain of rather limited practical value for biomedicine. Nevertheless, recent advancements have been made in application of signaling pathway science for real needs of prescription of the most effective drugs for individual patients. The methods for such prescription evaluate the degree of pathological changes in the signaling machinery based on two types of data: first, on the results of high-throughput gene expression profiling, and second, on the molecular pathway graphs that reflect interactions between the pathway members. For example, our algorithm OncoFinder evaluates the activation of molecular pathways on the basis of gene/protein expression data in the objects of the interest.Yet, the question of assessment of the relative importance for each gene product in a molecular pathway remains unclear unless one call for the methods of parameter sensitivity /stiffness analysis in the interactomic kinetic models of signaling pathway activation in terms of total concentrations of each gene product.Here we show two principal points: 1. First, the importance coefficients for each gene in pathways that were obtained using the extremely time- and labor-consuming stiffness analysis of full-scaled kinetic models generally differ from much easier-to-calculate expression-based pathway activation score (PAS) not more than by 30%, so the concept of PAS is kinetically justified. 2. Second, the use of pathway-based approach instead of distinct gene analysis, due to the law of large numbers, allows restoring the correlation between the similar samples that were examined using different transcriptome investigation techniques.

  19. Garlic-Derived S-Allylmercaptocysteine Ameliorates Nonalcoholic Fatty Liver Disease in a Rat Model through Inhibition of Apoptosis and Enhancing Autophagy

    PubMed Central

    Fung, Man-Lung; Liong, Emily C.; Chang, Raymond Chuen Chung; Ching, Yick-Pang; Tipoe, George L.

    2013-01-01

    Our previous study demonstrated that administration of garlic-derived antioxidant S-allylmercaptocysteine (SAMC) ameliorated hepatic injury in a nonalcoholic fatty liver disease (NAFLD) rat model. Our present study aimed to investigate the mechanism of SAMC on NAFLD-induced hepatic apoptosis and autophagy. Adult female rats were fed with a high-fat diet for 8 weeks to develop NAFLD with or without intraperitoneal injection of 200 mg/kg SAMC for three times per week. During NAFLD development, increased apoptotic cells and caspase-3 activation were observed in the liver. Increased apoptosis was modulated through both intrinsic and extrinsic apoptotic pathways. NAFLD treatment also enhanced the expression of key autophagic markers in the liver with reduced activity of LKB1/AMPK and PI3K/Akt pathways. Increased expression of proapoptotic regulator p53 and decreased activity of antiautophagic regulator mTOR were also observed. Administration of SAMC reduced the number of apoptotic cells through downregulation of both intrinsic and extrinsic apoptotic mechanisms. SAMC also counteracted the effects of NAFLD on LKB1/AMPK and PI3K/Akt pathways. Treatment with SAMC further enhanced hepatic autophagy by regulating autophagic markers and mTOR activity. In conclusion, administration of SAMC during NAFLD development in rats protects the liver from chronic injury by reducing apoptosis and enhancing autophagy. PMID:23861709

  20. Thioredoxin 1 in Prostate Tissue Is Associated with Gleason Score, Erythrocyte Antioxidant Enzyme Activity, and Dietary Antioxidants.

    PubMed

    Vance, Terrence M; Azabdaftari, Gissou; Pop, Elena A; Lee, Sang Gil; Su, L Joseph; Fontham, Elizabeth T H; Bensen, Jeannette T; Steck, Susan E; Arab, Lenore; Mohler, James L; Chen, Ming-Hui; Koo, Sung I; Chun, Ock K

    2015-01-01

    Background. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer. Methods. In this study, thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher's exact test. Results. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score (P = 0.01) and inversely associated with dietary antioxidant intake (P = 0.03). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (P = 0.01). No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (P = 0.04). Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants.

  1. A model to predict the onset of non-alcoholic fatty liver disease within 2 years in elderly adults.

    PubMed

    Lin, Ya-Jie; Gao, Xi-Mei; Pan, Wei-Wei; Gao, Shuai; Yu, Zhen-Zhen; Xu, Ping; Fan, Xiao-Peng

    2017-10-01

    Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic hepatitis, which leads to cirrhosis and hepatocellular carcinoma. However, it is difficult to identify subjects at high risk for NAFLD onset. This study aims to construct a model to predict the onset of NAFLD within 2 years in elderly adults. This study included and followed 3378 initial NAFLD-free subjects aged 60 years or over for 2 years, which were randomly divided into a training set and a validation set. NAFLD was diagnosed on ultrasound. Clinical and laboratory data were recorded at baseline. A model was constructed in the training set to predict the onset of NAFLD and validated in the validation set. Body mass index, hemoglobin, fasting blood glucose, and triglycerides were identified as predictors for the onset of NAFLD. A risk score (R) was calculated by them. It classified the subjects into low-risk group (R ≤ -2.88), moderate-risk group (-2.88 < R ≤ -1.26), and high-risk group (R > -1.26). In the training set, 4.68% of the participants in the low-risk group, 11.59% of the participants in the moderate-risk group, and 31.02% of the participants in the high-risk group developed NAFLD. In the validation set, 5.84% of the participants in the low-risk group, 10.57% of the participants in the moderate-risk group, and 29.44% of the participants in the high-risk group developed NAFLD. This study developed a model to predict the onset of NAFLD in elderly adults, which might provide indications for intervention to these subjects. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  2. Lifestyle changes for the treatment of nonalcoholic fatty liver disease: a review of observational studies and intervention trials.

    PubMed

    Zelber-Sagi, Shira; Godos, Justyna; Salomone, Federico

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is emerging as a major public health problem because of its association with increased cardiovascular and liver-related morbidity and mortality. Both genetic factors and lifestyle contribute to the pathogenesis of NAFLD. Lifestyle, including dietary habits and physical activity, is a modifiable risk factor and thus represents the main target for the prevention and treatment of NAFLD. In this review, we summarize the evidence regarding nutritional aspects (i.e. total energy intake, saturated fat and carbohydrates intake, certain foods or drinks and dietary patterns as a whole) in the treatment of NAFLD. In addition, we analyze the evidence concerning the independent effect of physical activity, including aerobic and resistance training, in the treatment of NAFLD. A therapeutic algorithm according to results from intervention trials is also provided for clinicians and other healthcare professionals involved in the management of NAFLD.

  3. Design and rationale of the WELCOME trial: A randomised, placebo controlled study to test the efficacy of purified long chainomega-3 fatty acid treatment in non-alcoholic fatty liver disease [corrected].

    PubMed

    Scorletti, E; Bhatia, L; McCormick, K G; Clough, G F; Nash, K; Calder, P C; Byrne, C D

    2014-03-01

    Non-alcoholic fatty liver disease (NAFLD) represents a range of liver conditions from simple fatty liver to progressive end stage liver disease requiring liver transplantation. NAFLD is common in the population and in certain sub groups (e.g. type 2 diabetes) up to 70% of patients may be affected. NAFLD is not only a cause of end stage liver disease and hepatocellular carcinoma, but is also an independent risk factor for type 2 diabetes and cardiovascular disease. Consequently, effective treatments for NAFLD are urgently needed. The WELCOME study is testing the hypothesis that treatment with high dose purified long chain omega-3 fatty acids will have a beneficial effect on a) liver fat percentage and b) two histologically validated algorithmically-derived biomarker scores for liver fibrosis. In a randomised double blind placebo controlled trial, 103 participants with NAFLD were randomised to 15-18months treatment with either 4g/day purified long chain omega-3 fatty acids (Omacor) or 4g/day olive oil as placebo. Erythrocyte percentage DHA and EPA enrichment (a validated proxy for hepatic enrichment) was determined by gas chromatography. Liver fat percentage was measured in three discrete liver zones by magnetic resonance spectroscopy (MRS). We also measured body fat distribution, physical activity and a range of cardiometabolic risk factors. Recruitment started in January 2010 and ended in June 2011. We identified 178 potential participants, and randomised 103 participants who met the inclusion criteria. The WELCOME study was approved by the local ethics committee (REC: 08/H0502/165; www.clinicalTrials.gov registration number NCT00760513). Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Estimation of Symptom Severity Scores for Patients with Schizophrenia Using ERP Source Activations during a Facial Affect Discrimination Task.

    PubMed

    Kim, Do-Won; Lee, Seung-Hwan; Shim, Miseon; Im, Chang-Hwan

    2017-01-01

    Precise diagnosis of psychiatric diseases and a comprehensive assessment of a patient's symptom severity are important in order to establish a successful treatment strategy for each patient. Although great efforts have been devoted to searching for diagnostic biomarkers of schizophrenia over the past several decades, no study has yet investigated how accurately these biomarkers are able to estimate an individual patient's symptom severity. In this study, we applied electrophysiological biomarkers obtained from electroencephalography (EEG) analyses to an estimation of symptom severity scores of patients with schizophrenia. EEG signals were recorded from 23 patients while they performed a facial affect discrimination task. Based on the source current density analysis results, we extracted voxels that showed a strong correlation between source activity and symptom scores. We then built a prediction model to estimate the symptom severity scores of each patient using the source activations of the selected voxels. The symptom scores of the Positive and Negative Syndrome Scale (PANSS) were estimated using the linear prediction model. The results of leave-one-out cross validation (LOOCV) showed that the mean errors of the estimated symptom scores were 3.34 ± 2.40 and 3.90 ± 3.01 for the Positive and Negative PANSS scores, respectively. The current pilot study is the first attempt to estimate symptom severity scores in schizophrenia using quantitative EEG features. It is expected that the present method can be extended to other cognitive paradigms or other psychological illnesses.

  5. Oxymatrine attenuates hepatic steatosis in non-alcoholic fatty liver disease rats fed with high fructose diet through inhibition of sterol regulatory element binding transcription factor 1 (Srebf1) and activation of peroxisome proliferator activated receptor alpha (Pparα).

    PubMed

    Shi, Li-juan; Shi, Lei; Song, Guang-yao; Zhang, He-fang; Hu, Zhi-juan; Wang, Chao; Zhang, Dong-hui

    2013-08-15

    The aim of this study was to examine the therapeutic effect of oxymatrine, a monomer isolated from the medicinal plant Sophora flavescens Ait, on the hepatic lipid metabolism in non-alcoholic fatty liver (NAFLD) rats and to explore the potential mechanism. Rats were fed with high fructose diet for 8 weeks to establish the NAFLD model, then were given oxymatrine treatment (40, 80, and 160 mg/kg, respectively) for another 8 weeks. Body weight gain, liver index, serum and liver lipids, and histopathological evaluation were measured. Enzymatic activity and gene expression of the key enzymes involved in the lipogenesis and fatty acid oxidation were assayed. The results showed that oxymatrine treatment reduced body weight gain, liver weight, liver index, dyslipidemia, and liver triglyceride level in a dose dependant manner. Importantly, the histopathological examination of liver confirmed that oxymatrine could decrease the liver lipid accumulation. The treatment also decreased the fatty acid synthase (FAS) enzymatic activity and increased the carnitine palmitoyltransferase 1A (CPT1A) enzymatic activity. Besides, oxymatrine treatment decreased the mRNA expression of sterol regulatory element binding transcription factor 1(Srebf1), fatty acid synthase (Fasn), and acetyl CoA carboxylase (Acc), and increased the mRNA expression of peroxisome proliferator activated receptor alpha (Pparα), carnitine palmitoyltransferase 1A (Cpt1a), and acyl CoA oxidase (Acox1) in high fructose diet induced NAFLD rats. These results suggested that the therapeutic effect of oxymatrine on the hepatic steatosis in high fructose diet induced fatty liver rats is partly due to down-regulating Srebf1 and up-regulating Pparα mediated metabolic pathways simultaneously. © 2013 Elsevier B.V. All rights reserved.

  6. Drug metabolism alterations in nonalcoholic fatty liver disease

    PubMed Central

    Merrell, Matthew D.; Cherrington, Nathan J.

    2013-01-01

    Drug-metabolizing enzymes play a vital role in the elimination of the majority of therapeutic drugs. The major organ involved in drug metabolism is the liver. Chronic liver diseases have been identified as a potential source of significant interindividual variation in metabolism. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting between 60 and 90 million Americans, yet the vast majority of NAFLD patients are undiagnosed. NAFLD encompasses a spectrum of pathologies, ranging from steatosis to nonalcoholic steatohepatitis and fibrosis. Numerous animal studies have investigated the effects of NAFLD on hepatic gene expression, observing significant alterations in mRNA, protein, and activity levels. Information on the effects of NAFLD in human patients is limited, though several significant investigations have recently been published. Significant alterations in the activity of drug-metabolizing enzymes may affect the clearance of therapeutic drugs, with the potential to result in adverse drug reactions. With the enormous prevalence of NAFLD, it is conceivable that every drug currently on the market is being given to patients with NAFLD. The current review is intended to present the results from both animal models and human patients, summarizing the observed alterations in the expression and activity of the phase I and II drug-metabolizing enzymes. PMID:21612324

  7. Non-alcoholic fatty liver disease–From the cardiologist perspective

    PubMed Central

    Sîrbu, Oana; Floria, Mariana; Dăscălița, Petru; Şorodoc, Victorița; Şorodoc, Laurențiu

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) includes a range of disorders characterized by excess accumulation of triglycerides within the liver. While simple steatosis may be clinically stable, non-alcoholic steatohepatitis (NASH) can be progressive. Inflammation is believed to be the driving force behind NASH and the progression to fibrosis and subsequent cirrhosis. NAFLD is globally considered a significant health concern not only because of its incidence but also because of its economic impact. The fact that NAFLD is associated with cardiovascular disease is widely recognized, as well as the fact that NAFLD patient mortality rises when such an association is present. In particular, NAFLD is associated with coronary and carotid atherosclerosis, endothelial dysfunction and arterial rigidity, ventricles function, valves morphology, congestive heart failure, and arrhythmias (especially atrial fibrillation). Additionally, the hypercoagulability status in NAFLD patient may be suggested by the presence of inflammatory and coagulation markers. In order to differentiate between milder forms and the more severe ones that necessitate aggressive therapy, individualized risk scores may be used. This narrative review will analyze and interpret the papers published in PubMed in the last 16 years, in an attempt to expand our understanding of the NASH as a possible cardiovascular risk factor. PMID:27389154

  8. Association between obstructive sleep apnea and non-alcoholic fatty liver disease: a systematic review and meta-analysis.

    PubMed

    Jin, Shanshan; Jiang, Suwen; Hu, Airong

    2018-01-15

    The relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) has been an issue of great concern. The primary purpose of this study was to determine the influence of OSA on the levels of liver enzymes including alanine transaminase (ALT) and aspartate transaminase (AST). The secondary purpose was to estimate the effect of OSA on the histological lesions of NAFLD, such as steatosis, lobular inflammation, ballooning degeneration, fibrosis, as well as NAFLD activity score (NAS). A systematic literature review using PubMed, Cochrane Library, Embase, and Ovid technologies from January 2007 to April 2017 was performed, and 9 studies (2272 participants) that met the selection criteria were evaluated. The present study demonstrated that OSA was related to ALT levels, but no significant correlation was found with AST levels. The subgroup analysis showed that the severity of OSA was associated with ALT levels, not with AST levels. The meta-regression analysis showed that age, sex, homeostasis model assessment, diabetes mellitus, body mass index, and waist circumference did not have a significant effect on the levels of ALT and AST. OSA was also found to be significantly correlated with steatosis, lobular inflammation, ballooning degeneration, and fibrosis, but was not correlated with NAS. OSA was independently related to the development and progression of NAFLD in terms of liver enzyme level and histological alterations. Future studies should investigate the possible relevant mechanisms, thereby guiding the exploration of potential therapeutic implications to prevent the progression of disease.

  9. Ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities in prostate cancer patients: influence of Gleason score, treatment and bone metastasis.

    PubMed

    Battisti, Vanessa; Maders, Liési D K; Bagatini, Margarete D; Battisti, Iara E; Bellé, Luziane P; Santos, Karen F; Maldonado, Paula A; Thomé, Gustavo R; Schetinger, Maria R C; Morsch, Vera M

    2013-04-01

    The relation between adenine nucleotides and cancer has already been described in literature. Considering that the enzymes ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) act together to control nucleotide levels, we aimed to investigate the role of these enzymes in prostate cancer (PCa). E-NPP and ADA activities were determined in serum and platelets of PCa patients and controls. We also verified the influence of the Gleason score, bone metastasis and treatment in the enzyme activities. Platelets and serum E-NPP activity increased, whereas ADA activity in serum decreased in PCa patients. In addition, Gleason score, metastasis and treatment influenced E-NPP and ADA activities. We may propose that E-NPP and ADA are involved in the development of PCa. Moreover, E-NPP and ADA activities are modified in PCa patients with distinct Gleason score, with bone metastasis, as well as in patients under treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Standardized Salvia miltiorrhiza extract suppresses hepatic stellate cell activation and attenuates steatohepatitis induced by a methionine-choline deficient diet in mice.

    PubMed

    Lee, Hak Sung; Son, Woo-Chan; Ryu, Jae-Eun; Koo, Bon Am; Kim, Yeong Shik

    2014-06-17

    The aim of this study was to examine the effect of standardized extract of Salvia miltiorrhiza (SME) on gene and protein expression of non-alcoholic steatohepatitis (NASH)-related factors in activated human hepatic stellate cells (HSC), and in mice with steatohepatitis induced by a methionine-choline deficient (MCD) diet. Male C57BL/6J mice were placed on an MCD or control diet for 8 weeks and SME (0, 0.1, 0.5 and 1 mg/kg body weight) was administered orally every other day for 4 or 6 weeks. HSCs from the LX-2 cell line were treated with transforming growth factor β-1 (TGF-β1) or TGF-β1 plus SME (0.1-10 μg/mL). To investigate the effect of SME on reactive oxygen species (ROS)-induced condition, LX-2 cells were treated with hydrogen peroxide (H2O2) or H2O2 plus SME (0.1-100 μg/mL). MCD administration for 12 weeks increased mRNA expression of tumor necrosis factor (TNF-α), TGF-β1, interleukin-1β (IL-1β), C-reactive protein (CRP), α-smooth muscle actin (α-SMA), type I collagen, matrix metalloproteinase-2 (MMP-2) and MMP-9. TGF-β1-induced LX-2 cells exhibited similar gene expression patterns. SME treatment significantly reduced the mRNA and protein expression of NASH-related factors in the mouse model and HSCs. Histopathological liver analysis showed improved non-alcoholic fatty liver disease (NAFLD) activity and fibrosis score in SME-treated mice. The in vivo studies showed that SME had a significant effect at low doses. These results suggest that SME might be a potential therapeutic candidate for NAFLD treatment.

  11. Validation of the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score): a multicenter prospective study.

    PubMed

    Niv, Y; Ilani, S; Levi, Z; Hershkowitz, M; Niv, E; Fireman, Z; O'Donnel, S; O'Morain, C; Eliakim, R; Scapa, E; Kalantzis, N; Kalantzis, C; Apostolopoulos, P; Gal, E

    2012-01-01

    The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice. This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohn's disease. The CECDAI was designed to evaluate three main parameters of Crohn's disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 - 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation. The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 - 0.985; Kappa 0.66; P < 0.001). There was no correlation between the CECDAI and the Crohn's Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components. A new scoring system of mucosal injury in Crohn's disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Obstructive Sleep Apnea Is Associated with Nonalcoholic Steatohepatitis and Advanced Liver Histology.

    PubMed

    Corey, Kathleen E; Misdraji, Joseph; Gelrud, Lou; King, Lindsay Y; Zheng, Hui; Malhotra, Atul; Chung, Raymond T

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are growing in prevalence in the USA. Existing data on the relationship between OSA and NAFLD are conflicting and limited by the use of various histologic definitions of nonalcoholic steatohepatitis (NASH). Using a robust definition of NASH in a large, well-characterized cohort, we sought to evaluate whether OSA was associated with NASH and advanced fibrosis. Two hundred and thirteen subjects undergoing weight loss surgery were queried for OSA and then underwent liver biopsy. NASH was defined, as recommended by the American Association for the Study of Liver Disease, by the presence of all of the following: >5 % macrovesicular steatosis, lobular inflammation, and hepatocyte ballooning. NAFLD activity score (NAS) was also determined for each subject. Subjects with OSA had significantly higher alanine and aspartate aminotransferase levels than subjects without OSA (ALT 54.1 vs. 37.7 U/L, P = 0.0007; AST 31.7 vs. 20.5 U/L, P = 0.0007). OSA was associated with the presence of NASH, and this remained significant after adjusting for age, gender, race, and diabetes mellitus (P = 0.03 OR 2.01; 95 %, 1.05-3.87). Steatosis grade, lobular inflammation grade, NAS score, and fibrosis stage were all significantly associated with the presence of OSA and remained so after adjustment. OSA is associated with elevated aminotransferase levels, the presence of NASH, and advanced NASH histology. Further studies are needed to evaluate the impact of OSA treatment on NASH.

  13. Obstructive Sleep Apnea is associated with Nonalcoholic Steatohepatitis and Advanced Liver Histology

    PubMed Central

    Corey, Kathleen E; Misdraji, Joseph; Gelrud, Lou; King, Lindsay Y.; Zheng, Hui; Malhotra, Atul; Chung, Raymond T

    2015-01-01

    Background and Aims Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are growing in prevalence in the United States. Existing data on the relationship between OSA and NAFLD is conflicting and limited by the use of various histologic definitions of nonalcoholic steatohepatitis (NASH). Using a robust definition of NASH in a large, well-characterized cohort we sought to evaluate whether OSA was associated with NASH and advanced fibrosis. Methods Two hundred thirteen subjects undergoing weight loss surgery were queried for OSA and then underwent liver biopsy. NASH was defined, as recommended by the American Association for the Study of Liver Disease, by the presence of all of the following: >5% macrovesicular steatosis, lobular inflammation and hepatocyte ballooning. NAFLD activity score (NAS) was also determined for each subject. Results Subjects with OSA had significantly higher alanine and aspartate aminotransferase levels than subjects without OSA (ALT 54.1 U/L vs. 37.7 U/L, P=0.0007; AST 31.7 U/L vs. 20.5 U/L, P=0.0007). OSA was associated with the presence of NASH and this remained significant after adjusting for age, gender, race, and diabetes mellitus (P =0.03 OR, 2.01; 95%, 1.05-3.87). Steatosis grade, lobular inflammation grade, NAS score and fibrosis stage were all significantly associated with the presence of OSA and remained so after adjustment. Conclusions OSA is associated with elevated aminotransferase levels, the presence of NASH and advanced NASH histology. Further studies are needed to evaluate the impact of OSA treatment on NASH. PMID:25840922

  14. Heterozygous Hfe gene deletion leads to impaired glucose homeostasis, but not liver injury in mice fed a high-calorie diet.

    PubMed

    Britton, Laurence; Jaskowski, Lesley; Bridle, Kim; Santrampurwala, Nishreen; Reiling, Janske; Musgrave, Nick; Subramaniam, V Nathan; Crawford, Darrell

    2016-06-01

    Heterozygous mutations of the Hfe gene have been proposed as cofactors in the development and progression of nonalcoholic fatty liver disease (NAFLD). Homozygous Hfe deletion previously has been shown to lead to dysregulated hepatic lipid metabolism and accentuated liver injury in a dietary mouse model of NAFLD We sought to establish whether heterozygous deletion of Hfe is sufficient to promote liver injury when mice are exposed to a high-calorie diet (HCD). Eight-week-old wild-type and Hfe(+/-) mice received 8 weeks of a control diet or HCD Liver histology and pathways of lipid and iron metabolism were analyzed. Liver histology demonstrated that mice fed a HCD had increased NAFLD activity score (NAS), steatosis, and hepatocyte ballooning. However, liver injury was unaffected by Hfe genotype. Hepatic iron concentration (HIC) was increased in Hfe(+/-) mice of both dietary groups. HCD resulted in a hepcidin-independent reduction in HIC Hfe(+/-) mice demonstrated raised fasting serum glucose concentrations and HOMA-IR score, despite unaltered serum adiponectin concentrations. Downstream regulators of hepatic de novo lipogenesis (pAKT, SREBP-1, Fas, Scd1) and fatty acid oxidation (AdipoR2, Pparα, Cpt1) were largely unaffected by genotype. In summary, heterozygous Hfe gene deletion is associated with impaired iron and glucose metabolism. However, unlike homozygous Hfe deletion, heterozygous gene deletion did not affect lipid metabolism pathways or liver injury in this model. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  15. AutoDock-GIST: Incorporating Thermodynamics of Active-Site Water into Scoring Function for Accurate Protein-Ligand Docking.

    PubMed

    Uehara, Shota; Tanaka, Shigenori

    2016-11-23

    Water plays a significant role in the binding process between protein and ligand. However, the thermodynamics of water molecules are often underestimated, or even ignored, in protein-ligand docking. Usually, the free energies of active-site water molecules are substantially different from those of waters in the bulk region. The binding of a ligand to a protein causes a displacement of these waters from an active site to bulk, and this displacement process substantially contributes to the free energy change of protein-ligand binding. The free energy of active-site water molecules can be calculated by grid inhomogeneous solvation theory (GIST), using molecular dynamics (MD) and the trajectory of a target protein and water molecules. Here, we show a case study of the combination of GIST and a docking program and discuss the effectiveness of the displacing gain of unfavorable water in protein-ligand docking. We combined the GIST-based desolvation function with the scoring function of AutoDock4, which is called AutoDock-GIST. The proposed scoring function was assessed employing 51 ligands of coagulation factor Xa (FXa), and results showed that both scoring accuracy and docking success rate were improved. We also evaluated virtual screening performance of AutoDock-GIST using FXa ligands in the directory of useful decoys-enhanced (DUD-E), thus finding that the displacing gain of unfavorable water is effective for a successful docking campaign.

  16. Reduction of sitting time has a positive effect on the decrease of insulin resistance in patients with non-alcoholic fatty liver disease

    PubMed Central

    Sabinicz, Anna; Maciejewska, Dominika; Kaczorowska, Małgorzata; Ryterska, Karina; Jamioł-Milc, Dominika; Wyszomirska-Raszeja, Joanna; Gutowska, Izabela

    2016-01-01

    Introduction Non-alcoholic fatty liver disease (NAFLD) affects a large part of the human population. One of the major environmental factors associated with the risk of NAFLD is the lack of physical activity. Aim To compare the level of physical activity and the insulin resistance in NAFLD patients. Material and methods Thirty patients with NAFLD underwent a six-month dietary intervention based on the principles of classical dietetics. Data about diet and physical activity was based on 72-hour nutrition diaries and International Physical Activity Questionnaire (IPAQ). Standard blood biochemical analyses were carried out before and after diet at the University Hospital Laboratory. Results The study showed that total physical activity and physical activity in leisure time are negatively correlated with insulin resistance (HOMA-IR) (p < 0.05). Insulin (p < 0.05), body weight (p < 0.05), and waist-hip ratio (WHR) (p < 0.05) were also negatively correlated with physical activity in free time. In addition, we noticed a positive correlation between sitting time and the risk of insulin resistance, in the case of HOMA-IR and insulin concentration (p < 0.05). Conclusions Dietary intervention and a physical activity plan are important factors in the treatment of non-alcoholic fatty liver disease. Taking regular exercise increases insulin sensitivity and prevents further development of the disease. It seems that diet and physical activity are not the only one risk factors of NAFLD. Our study reveals that the reduction of sitting time has a positive effect on the level of insulin and it reduces insulin resistance in patients with NAFLD. PMID:28053680

  17. Combined Adiponectin Deficiency and Resistance in Obese Patients: Can It Solve Part of the Puzzle in Nonalcoholic Steatohepatitis.

    PubMed

    Salman, Ahmed; Hegazy, Mona; AbdElfadl, Soheir

    2015-06-15

    Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, nonalcoholic steatohepatitis (NASH) and fibrosis in obese patients identifies the risk group with increased incidence of liver-related deaths. To clarify the role of serum adiponectin and its receptor liver gene expression in the progression of liver damage in NAFLD. Fifty four (54) obese patients with NAFLD preliminary diagnosed by liver ultra-sound were recruited. Full medical history, anthropometric measurement, biochemical studies, serum adiponectin level, liver biopsy for histological examination and NAS score to identify NASH patients, and assessment of adiponectin receptor gene expression by RT-PCR, were conducted for each patients. Fifteen ages matched average weight healthy adult had been chosen as a control for serum adiponectin level. According to NAS score, patients were divided into non- NASH (8 patients), and NASH (46 patients). Serum adiponectin level was significantly lower in NAFLD patients compared to normal participants (p < 0.004). Serum adiponectin level was lower in NASH patients (4.437 ± 2.569 ng/dl in NASH vs. 5.138 ± 2.841 ng/dl in non-NASH). Adiponectin receptor liver gene expression was lower in NASH patients (0.8459 ± 0.4671 vs. 1.0688 ± 0.3965 in non-NASH). Both adiponectin deficiency and resistance had a role in progression of simple liver steatosis to severe injury in obese patients.

  18. Diagnosis and management of cardiovascular risk in nonalcoholic fatty liver disease.

    PubMed

    Lonardo, Amedeo; Ballestri, Stefano; Targher, Giovanni; Loria, Paola

    2015-05-01

    Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as an important cardiovascular risk (CVR) factor. This is a narrative clinical review aimed at answering how diagnosis and management of CVR should be conducted in the individual patient with NAFLD. To this end, the authors performed an extensive search of the existing literature on PubMed (1993-2014) using pertinent keywords. To date, CVR among patients with NAFLD might be assessed with the Framingham risk score equation or other risk calculators, to be adapted to the true CVR in the specific population being assessed; however, the use of these CVR calculators needs to be validated by future studies in larger cohorts of NAFLD patients of various ethnic backgrounds in order to substantiate their clinical relevance as a foundation for the primary prevention of cardiovascular diseases in this group of patients. Early and aggressive drug treatment of CVR should be started in NAFLD patients with a history of cardiovascular events, established diabetes or who are at high (calculated) CVR. Whether such an aggressive pharmacological approach is also justified in patients with NAFLD, who are at intermediate or low CVR, remains debatable. Currently, there are no clinical trials showing that the treatment of NAFLD per se (either associated or unassociated with traditional CVR factors) will result in decreased risk of cardiovascular events. Accordingly, drug treatment should be better individualized, aiming at correcting all the coexisting cardio-metabolic risk factors of the individual patient with NAFLD. To this end, an overview of the lifestyle interventions and the available drugs is offered, emphasis being conveyed to statins and metformin, which promise to cover worrying complications of NAFLD such as the risk of developing hepatocellular carcinoma.

  19. Randomized clinical trial: benefits of aerobic physical activity for 24 weeks in postmenopausal women with nonalcoholic fatty liver disease.

    PubMed

    Rezende, Rosamar E F; Duarte, Sebastião M B; Stefano, Jose T; Roschel, Hamilton; Gualano, Bruno; de Sá Pinto, Ana L; Vezozzo, Denise C P; Carrilho, Flair J; Oliveira, Claudia P

    2016-08-01

    The aim of the study was to evaluate the effectiveness of aerobic physical activity in reducing the frequency of hepatic steatosis and metabolic and cardiovascular risk in postmenopausal women with nonalcoholic fatty liver disease (NAFLD). Forty sedentary postmenopausal women (mean age 55.3 ± 8.0 y) with biopsy-proven NAFLD were randomly divided into two groups: an exercising group (19 participants) and a control group (nonexercising, 21 participants). The exercise group underwent a supervised aerobic physical activity program of 120 min/wk for 24 weeks. The anthropometric parameters; body composition; hepatic, lipid, and glycemic profiles; homeostasis model assessment of insulin resistance index; cytokines; transient elastography (FibroScan; liver stiffness/controlled attenuation parameter); and cardiopulmonary exercise test were evaluated at baseline and after 24 weeks of protocol. At baseline there were no significant differences in anthropometric, metabolic, and inflammatory parameters-stiffness and liver fat content by FibroScan between the groups. After 24 weeks, we observed a decrease of waist circumference, an increase of high-density lipoprotein cholesterol levels (P < 0.05), and improved cardiopulmonary functional capacity in the exercise group. In addition, the controlled attenuation parameter analysis showed no significant decrease of hepatic steatosis in the exercise group. With regard to the systemic inflammation, there were, however, no significant differences in the cytokines between the groups. An aerobic physical activity program of 24 weeks in NAFLD postmenopausal women showed improvement in some variables such as waist circumference, high-density lipoprotein cholesterol, and cardiopulmonary performance that may be beneficial in improving cardiovascular risk factors in this population.

  20. Validity and reliability of Nintendo Wii Fit balance scores.

    PubMed

    Wikstrom, Erik A

    2012-01-01

    Interactive gaming systems have the potential to help rehabilitate patients with musculoskeletal conditions. The Nintendo Wii Balance Board, which is part of the Wii Fit game, could be an effective tool to monitor progress during rehabilitation because the board and game can provide objective measures of balance. However, the validity and reliability of Wii Fit balance scores remain unknown. To determine the concurrent validity of balance scores produced by the Wii Fit game and the intrasession and intersession reliability of Wii Fit balance scores. Descriptive laboratory study. Sports medicine research laboratory. Forty-five recreationally active participants (age = 27.0 ± 9.8 years, height = 170.9 ± 9.2 cm, mass = 72.4 ± 11.8 kg) with a heterogeneous history of lower extremity injury. Participants completed a single-limb-stance task on a force plate and the Star Excursion Balance Test (SEBT) during the first test session. Twelve Wii Fit balance activities were completed during 2 test sessions separated by 1 week. Postural sway in the anteroposterior (AP) and mediolateral (ML) directions and the AP, ML, and resultant center-of-pressure (COP) excursions were calculated from the single-limb stance. The normalized reach distance was recorded for the anterior, posteromedial, and posterolateral directions of the SEBT. Wii Fit balance scores that the game software generated also were recorded. All 96 of the calculated correlation coefficients among Wii Fit activity outcomes and established balance outcomes were interpreted as poor (r < 0.50). Intrasession reliability for Wii Fit balance activity scores ranged from good (intraclass correlation coefficient [ICC] = 0.80) to poor (ICC = 0.39), with 8 activities having poor intrasession reliability. Similarly, 11 of the 12 Wii Fit balance activity scores demonstrated poor intersession reliability, with scores ranging from fair (ICC = 0.74) to poor (ICC = 0.29). Wii Fit balance activity scores had poor concurrent validity

  1. Development and Initial Validation of the Macrophage Activation Syndrome/Primary Hemophagocytic Lymphohistiocytosis Score, a Diagnostic Tool that Differentiates Primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome.

    PubMed

    Minoia, Francesca; Bovis, Francesca; Davì, Sergio; Insalaco, Antonella; Lehmberg, Kai; Shenoi, Susan; Weitzman, Sheila; Espada, Graciela; Gao, Yi-Jin; Anton, Jordi; Kitoh, Toshiyuki; Kasapcopur, Ozgur; Sanner, Helga; Merino, Rosa; Astigarraga, Itziar; Alessio, Maria; Jeng, Michael; Chasnyk, Vyacheslav; Nichols, Kim E; Huasong, Zeng; Li, Caifeng; Micalizzi, Concetta; Ruperto, Nicolino; Martini, Alberto; Cron, Randy Q; Ravelli, Angelo; Horne, AnnaCarin

    2017-10-01

    To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from <1% for a score of <11 to >99% for a score of  ≥123. A cutoff value of ≥60 revealed the best performance in discriminating pHLH from MAS. The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The effects of activating prior topic and metacognitive knowledge on text comprehension scores.

    PubMed

    Kostons, Danny; van der Werf, Greetje

    2015-09-01

    Research on prior knowledge activation has consistently shown that activating learners' prior knowledge has beneficial effects on learning. If learners activate their prior knowledge, this activated knowledge serves as a framework for establishing relationships between the knowledge they already possess and new information provided to them. Thus far, prior knowledge activation has dealt primarily with topic knowledge in specific domains. Students, however, likely also possess at least some metacognitive knowledge useful in those domains, which, when activated, should aid in the deployment of helpful strategies during reading. In this study, we investigated the effects of both prior topic knowledge activation (PTKA) and prior metacognitive knowledge activation (PMKA) on text comprehension scores. Eighty-eight students in primary education were randomly distributed amongst the conditions of the 2 × 2 (PTKA yes/no × PMKA yes/no) designed experiment. Results show that activating prior metacognitive knowledge had a beneficial effect on text comprehension, whereas activating prior topic knowledge, after correcting for the amount of prior knowledge, did not. Most studies deal with explicit instruction of metacognitive knowledge, but our results show that this may not be necessary, specifically in the case of students who already have some metacognitive knowledge. However, existing metacognitive knowledge needs to be activated in order for students to make better use of this knowledge. © 2015 The British Psychological Society.

  3. Multibiomarker disease activity score and C-reactive protein in a cross-sectional observational study of patients with rheumatoid arthritis with and without concomitant fibromyalgia.

    PubMed

    Lee, Yvonne C; Hackett, James; Frits, Michelle; Iannaccone, Christine K; Shadick, Nancy A; Weinblatt, Michael E; Segurado, Oscar G; Sasso, Eric H

    2016-04-01

    To examine the association between a multibiomarker disease activity (MBDA) score, CRP and clinical disease activity measures among RA patients with and without concomitant FM. In an observational cohort of patients with established RA, we performed a cross-sectional analysis comparing MBDA scores with CRP by rank correlation and cross-classification. MBDA scores, CRP and clinical measures of disease activity were compared between patients with RA alone and RA with concomitant FM (RA and FM) by univariate and multivariate analyses. CRP was ⩽1.0 mg/dl for 184 of 198 patients (93%). MBDA scores correlated with CRP (r = 0.755, P < 0.001), but were often discordant, being moderate or high for 19%, 55% and 87% of patients with CRP ⩽0.1, 0.1 to ⩽0.3, or 0.3 to ⩽1.0 mg/dl, respectively. Among patients with CRP ⩽1.0 mg/dl, swollen joint count (SJC) increased linearly across levels of MBDA score, both with (P = 0.021) and without (P = 0.004) adjustment for CRP, whereas CRP was not associated with SJC. The 28-joint-DAS-CRP, other composite measures, and their non-joint-count component measures were significantly greater for patients with RA and FM (n = 25) versus RA alone (n = 173) (all P ⩽ 0.005). MBDA scores and CRP were similar between groups. MBDA scores frequently indicated RA disease activity when CRP did not. Neither one was significantly greater among patients with RA and FM versus RA alone. Thus, MBDA score may be a useful objective measure for identifying RA patients with active inflammation when CRP is low (⩽1.0 mg/dl), including RA patients with concomitant FM. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  4. Hepatocellular carcinoma in a mouse model fed a choline-deficient, L-amino acid-defined, high-fat diet.

    PubMed

    Ikawa-Yoshida, Ayae; Matsuo, Saori; Kato, Atsuhiko; Ohmori, Yusuke; Higashida, Atsuko; Kaneko, Eiji; Matsumoto, Masahiko

    2017-08-01

    Hepatocellular carcinoma (HCC) is a common cancer worldwide and represents the outcome of the natural history of chronic liver disease. The growing rates of HCC may be partially attributable to increased numbers of people with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). However, details of the liver-specific molecular mechanisms responsible for the NAFLD-NASH-HCC progression remain unclear, and mouse models that can be used to explore the exact factors that influence the progression of NAFLD/NASH to the more chronic stages of liver disease and subsequent HCC are not yet fully established. We have previously reported a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) as a dietary NASH model with rapidly progressive liver fibrosis in mice. The current study in C57BL/6J mice fed CDAHFD provided evidence for the chronic persistence of advanced hepatic fibrosis in NASH and disease progression towards HCC in a period of 36 weeks. When mice fed CDAHFD were switched back to a standard diet, hepatic steatosis was normalized and NAFLD activity score improved, but HCC incidence increased and the phenotype of fibrosis-associated HCC development was observed. Moreover, when mice continued to be fed CDAHFD for 60 weeks, HCC further developed without severe body weight loss or carcinogenesis in other organs. The autochthonous tumours showed a variety of histological features and architectural patterns including trabecular, pseudoglandular and solid growth. The CDAHFD mouse model might be a useful tool for studying the development of HCC from NAFLD/NASH, and potentially useful for better understanding pathological changes during hepatocarcinogenesis. © 2017 The Authors. International Journal of Experimental Pathology published by John Wiley & Sons Ltd on behalf of Company of the International Journal of Experimental Pathology (CIJEP).

  5. Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation.

    PubMed

    Gadd, Victoria L; Patel, Preya J; Jose, Sara; Horsfall, Leigh; Powell, Elizabeth E; Irvine, Katharine M

    2016-01-01

    Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence. Peripheral blood monocyte surface marker (CD14, CD16, CD163, CSF1R, CCR2, CCR4, CCR5, CXCR3, CXCR4, CX3CR1, HLA-DR, CD62L, SIGLEC-1) expression and capacity for phagocytosis, oxidative burst and LPS-stimulated TNF production were assessed in patients with hepatitis C (HCV) (n = 39) or non-alcoholic fatty liver disease (NAFLD) (n = 34) (classified as non-advanced disease, compensated cirrhosis and decompensated cirrhosis) and healthy controls (n = 11) by flow cytometry. The selected markers exhibited similar monocyte-subset-specific expression patterns between patients and controls. Monocyte phenotypic signatures differed between NAFLD and HCV patients, with an increased proportion of CD16+ non-classical monocytes in NAFLD, but increased expression of CXCR3 and CXCR4 in HCV. In both cohorts, monocyte CCR2 expression was reduced and CCR4 elevated over controls. CD62L expression was specifically elevated in patients with decompensated cirrhosis and positively correlated with the model-for-end-stage-liver-disease score. Functionally, monocytes from patients with decompensated cirrhosis had equal phagocytic capacity, but displayed features of dysfunction, characterised by lower HLA-DR expression and blunted oxidative responses. Lower monocyte TNF production in response to LPS stimulation correlated with time to death in 7 (46%) of the decompensated patients who died within 8 months of recruitment. Chronic HCV and NAFLD differentially affect circulating monocyte phenotype, suggesting specific injury-induced signals may contribute to hepatic monocyte recruitment and systemic activation state. Monocyte function, however, was similarly impaired in patients with both HCV and NAFLD, particularly in advanced disease, which likely contributes to the increased

  6. Examining the Relationship Between the Functional Movement Screen and the Landing Error Scoring System in an Active, Male Collegiate Population.

    PubMed

    Everard, Eoin M; Harrison, Andrew J; Lyons, Mark

    2017-05-01

    Everard, EM, Harrison, AJ, and Lyons, M. Examining the relationship between the functional movement screen and the landing error scoring system in an active, male collegiate population. J Strength Cond Res 31(5): 1265-1272, 2017-In recent years, there has been an increasing focus on movement screening as the principal aspect of preparticipation testing. Two of the most common movement screening tools are the Functional Movement Screen (FMS) and the Landing Error Scoring System (LESS). Several studies have examined the reliability and validity of these tools, but so far, there have been no studies comparing the results of these 2 screening tools against each other. Therefore, the purpose of this study was to determine the relationship between FMS scores and LESS scores. Ninety-eight male college athletes actively competing in sport (Gaelic games, soccer, athletics, boxing/mixed martial arts, Olympic weightlifting) participated in the study and performed the FMS and LESS screens. Both the 21-point and 100-point scoring systems were used to score the FMS. Spearman's correlation coefficients were used to determine the relationship between the 2 screening scores. The results showed a significant moderate correlation between FMS and LESS scores (rho 100 and 21 point = -0.528; -0.487; p < 0.001). In addition, r values of 0.26 and 0.23 indicate a poor shared variance between the 2 screens. The results indicate that performing well in one of the screens does not necessarily equate to performing well in the other. This has practical implications as it highlights that both screens may assess different movement patterns and should not be used as a substitute for each other.

  7. Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab.

    PubMed

    López De Padilla, Consuelo M; Crowson, Cynthia S; Hein, Molly S; Strausbauch, Michael A; Aggarwal, Rohit; Levesque, Marc C; Ascherman, Dana P; Oddis, Chester V; Reed, Ann M

    2015-01-01

    The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab. In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed. Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab. IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.

  8. Nimesulide, a cyclooxygenase-2 selective inhibitor, suppresses obesity-related non-alcoholic fatty liver disease and hepatic insulin resistance through the regulation of peroxisome proliferator-activated receptor γ.

    PubMed

    Tsujimoto, Shunsuke; Kishina, Manabu; Koda, Masahiko; Yamamoto, Yasutaka; Tanaka, Kohei; Harada, Yusuke; Yoshida, Akio; Hisatome, Ichiro

    2016-09-01

    Cyclooxygenase (COX)-2 selective inhibitors suppress non-alcoholic fatty liver disease (NAFLD); however, the precise mechanism of action remains unknown. The aim of this study was to examine how the COX-2 selective inhibitor nimesulide suppresses NAFLD in a murine model of high-fat diet (HFD)‑induced obesity. Mice were fed either a normal chow diet (NC), an HFD, or HFD plus nimesulide (HFD-nime) for 12 weeks. Body weight, hepatic COX-2 mRNA expression and triglyceride accumulation were significantly increased in the HFD group. Triglyceride accumulation was suppressed in the HFD-nime group. The mRNA expression of hepatic peroxisome proliferator-activated receptor γ (PPARγ) and the natural PPARγ agonist 15-deoxy-Δ12,14-prostaglandin J2 (15d‑PGJ2) were significantly increased in the HFD group and significantly suppressed in the HFD-nime group. Glucose metabolism was impaired in the HFD group compared with the NC group, and it was significantly improved in the HFD-nime group. In addition, the plasma insulin levels in the HFD group were increased compared with those in the NC group, and were decreased in the HFD-nime group. These results indicate that HFD-induced NAFLD is mediated by the increased hepatic expression of COX-2. We suggest that the production of 15d-PGJ2, which is mediated by COX-2, induces NAFLD and hepatic insulin resistance by activating PPARγ. Furthermore, the mRNA expression of tissue inhibitor of metalloproteinases-1 (TIMP‑1), procollagen-1 and monocyte chemoattractant protein-1 (MCP-1), as well as the number of F4/80-positive hepatic (Kupffer) cells, were significantly increased in the HFD group compared with the NC group, and they were reduced by nimesulide. In conclusion, COX-2 may emerge as a molecular target for preventing the development of NAFLD and insulin resistance in diet-related obesity.

  9. In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis.

    PubMed

    Africa, Jonathan A; Behling, Cynthia A; Brunt, Elizabeth M; Zhang, Nan; Luo, Yunjun; Wells, Alan; Hou, Jiayi; Belt, Patricia H; Kohil, Rohit; Lavine, Joel E; Molleston, Jean P; Newton, Kimberly P; Whitington, Peter F; Schwimmer, Jeffrey B

    2018-03-01

    Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001). Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague-Dawley Rats.

    PubMed

    Al Zarzour, Raghdaa Hamdan; Ahmad, Mariam; Asmawi, Mohd Zaini; Kaur, Gurjeet; Saeed, Mohammed Ali Ahmed; Al-Mansoub, Majed Ahmed; Saghir, Sultan Ayesh Mohammed; Usman, Nasiba Salisu; Al-Dulaimi, Dhamraa W; Yam, Mun Fei

    2017-07-18

    Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri ( P. niruri ) . NAFLD was induced in male Sprague-Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC-HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.

  11. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.

    PubMed

    Stål, Per

    2015-10-21

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

  12. Increased risk of nonalcoholic fatty liver disease with occupational stress in Chinese policemen: A 4-year cohort study.

    PubMed

    Li, Chen; Xing, Jing-Jing; Shan, An-Qi; Leng, Ling; Liu, Jin-Chuan; Yue, Song; Yu, Hao; Chen, Xi; Tian, Feng-Shi; Tang, Nai-Jun

    2016-11-01

    Nonalcoholic fatty liver disease (NAFLD) and occupational stress have been recognized as major public health concerns. We aimed to explore whether occupational stress was associated with NAFLD in a police population.A total of 6559 male police officers were recruited for this prospective study in April 2007. Among them, 2367 eligible subjects participated in follow-up from 2008 to 2011. NAFLD was diagnosed based on standard criteria. Occupational stress was evaluated by Occupational Stress Inventory-Revised scores.The incidence of NAFLD was 31.2% in the entire police. After adjusting for traditional risk factors, moderate occupational stress (MOS), high occupational stress (HOS), and high personal strain (HPS) were risk factors (MOS: hazard ratio [HR] = 1.237, 95% confidence interval [CI] = 1.049-1.460; HOS: HR = 1.727, 95% CI = 1.405-2.124; HPS: HR = 3.602, 95% CI = 1.912-6.787); and low occupational stress (LOS) and low personal strain (LPS) were protective factors (LOS: HR = 0.366, 95% CI = 0.173-0.776; LPS: HR = 0.490, 95% CI = 0.262-0.919) for NAFLD in the entire police cohort. HOS and HPS remained robust among traffic police.HOS and HPS were independent predictors for the development of NAFLD in a Chinese police population. Additional future prospective investigations are warranted to validate our findings.

  13. Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague–Dawley Rats

    PubMed Central

    Al Zarzour, Raghdaa Hamdan; Ahmad, Mariam; Asmawi, Mohd. Zaini; Kaur, Gurjeet; Al-Mansoub, Majed Ahmed; Saghir, Sultan Ayesh Mohammed; Usman, Nasiba Salisu; Al-Dulaimi, Dhamraa W.; Yam, Mun Fei

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague–Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC–HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis. PMID:28718838

  14. Continuous metabolic syndrome risk score, body mass index percentile, and leisure time physical activity in American children.

    PubMed

    Okosun, Ike S; Boltri, John M; Lyn, Rodney; Davis-Smith, Monique

    2010-08-01

    The objective of this study was to determine independent and joint association of body mass index (BMI) percentile and leisure time physical activity (LTPA) with continuous metabolic syndrome (cMetS) risk score in 12- to 17-year-old American children. The 2003 to 2004 US National Health and Nutrition Examination Survey data were used for this investigation. LTPA was determined by self-report. cMetS risk score was calculated using standardized residuals of arterial blood pressure, triglycerides, glucose, waist circumference, and high-density lipoprotein cholesterol. Multiple linear regression analysis was used to evaluate association of BMI percentile and LTPA with cMetS risk score, adjusting for confounders. Increased BMI percentile and LTPA were each associated with increased and decreased cMetS risk score, respectively ((P<.01). There was a gradient of increasing cMetS risk score by BMI percentile cutpoints, from healthy weight (-0.77) to overweight (3.43) and obesity (6.40) ((P<.05). A gradient of decreasing cMetS risk score from sedentary (0.88) to moderate (0.17) and vigorous (-0.42) LTPA levels was also observed (P<.01). The result of this study suggests that promoting LTPA at all levels of weight status may help to reverse the increasing trends of metabolic syndrome in US children. (c) 2010 Wiley Periodicals, Inc.

  15. Magnetic resonance imaging and transient elastography in the management of Nonalcoholic Fatty Liver Disease (NAFLD).

    PubMed

    Han, Ma Ai Thanda; Saouaf, Rola; Ayoub, Walid; Todo, Tsuyoshi; Mena, Edward; Noureddin, Mazen

    2017-04-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and cirrhosis worldwide and the second most common cause of liver transplantation in major medical centers. Because liver steatosis and fibrosis severity are related to disease morbidity and mortality, the extent of disease, and disease progression, they need to be assessed and monitored. In addition, innovation with new drug developments requires disease staging and monitoring in both phase 2 and 3 clinical trials. Currently, disease assessment in both clinical practice and research is mostly performed by liver biopsy, an invasive, procedure with risks. Noninvasive, highly accurate tests are needed that could be used in clinical trials as surrogate endpoints and in clinical practice for monitoring patients. Area Covered: We discuss noninvasive tests, transient elastography (TE) with controlled attenuation parameter (CAP), magnetic resonance imaging (MRI), and MR elastography (MRE), summarize the available evidence of their usefulness for assessing steatosis and fibrosis. Therefore they could be used as clinical trials outcomes and in disease monitoring in clinical practice. Expert Commentary: TE with CAP, MRI and MRE are highly accurate noninvasive diagnostic tools for quantifying hepatic steatosis and fibrosis. Therefore they could be used as clinical trials outcomes and in disease monitoring in clinical practice.

  16. Association Between the Severity of Nocturnal Hypoxia in Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Damage

    PubMed Central

    Cakmak, Erol; Duksal, Faysal; Altinkaya, Engin; Acibucu, Fettah; Dogan, Omer Tamer; Yonem, Ozlem; Yilmaz, Abdulkerim

    2015-01-01

    Background: Obstructive sleep apnea (OSA) is a major disease that can cause significant mortality and morbidity. Chronic intermittent hypoxia is a potential causal factor in the progression from fatty liver to nonalcoholic steatohepatitis. Objectives: This study evaluated the association between the degree of liver steatosis and severity of nocturnal hypoxia. Patients and Methods: In this study, between December 2011 and December 2013, patients with ultrasound-diagnosed NAFLD evaluated by standart polysomnography were subsequentally recorded. Patients with alcohol use, viral hepatitis and other chronic liver diseases were excluded. We analyzed polysomnographic parameters, steatosis level and severity of obstructive sleep apnea (OSA) in consideration of body mass index (BMI), biochemical tests and ultrasonographic liver data of 137 subjects. Patients with sleep apnea and AHI scores of < 5, 5 - 14, 15 - 29 and ≥30 are categorized as control, mild, moderate and severe, respectively. Results: One hundred and thirty-seven patients (76 women, 61 men) with a mean age of 55.75 ± 10.13 years who underwent polysomnography were included in the study. Of 118 patients diagnosed with OSA, 19 (16.1%) had mild OSA, 39 (33.1%) moderate OSA and 60 (50.8%) severe OSA. Nineteen cases formed the control group. Apnea/hypopnea index and oxygen desaturation index (ODI) values were significantly higher in moderate and severe non-alcoholic fatty liver disease (NAFLD) compared to the non-NAFLD group. Mean nocturnal SpO2 values were significantly lower in mild NAFLD and severe NAFLD compared to the non-NAFLD group. Lowest O2 saturation (LaSO2) was found low in mild, moderate and severe NAFLD compared to the non-NAFLD group in a statistically significant manner. Conclusions: We assessed polysomnographic parameters of AHI, ODI, LaSO2 and mean nocturnal SpO2 levels, which are especially important in the association between NAFLD and OSAS. We think that it is necessary to be attentive

  17. Chlorogenic acid alleviates autophagy and insulin resistance by suppressing JNK pathway in a rat model of nonalcoholic fatty liver disease.

    PubMed

    Yan, Hua; Gao, Yan-Qiong; Zhang, Ying; Wang, Huan; Liu, Gui-Sheng; Lei, Jian-Yuan

    2018-06-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases around the world and commonly associated with insulin resistance and hyperlipidemia. Chlorogenic acid (CG) was reported to have insulinsensitizing activity and exert hypocholesterolemic and hypoglycemic effect. However, the involvement of CG in NAFLD remains far from being addressed. In this study, a high-fat diet-induced NAFLD rat model was used to investigate the biological roles and underlying mechanism of CG in NAFLD. The results showed that high-fat diet-fed rats exhibited an increase in body weight, glucose tolerance, liver injury, insulin resistance, as well as autophagy and C-Jun N-terminal kinase (JNK) pathway. Nevertheless, all these effects were alleviated by CG treatment. Moreover, angiotensin treatment in CG group activated the JNK pathway, and promoted autophagy, insulin resistance, and liver injury. In conclusion, our findings demonstrated that CG ameliorated liver injury and insulin resistance by suppressing autophagy via inactivation of JNK pathway in a rat model of NAFLD. Therefore, CG might be a potential application for the treatment of NAFLD.

  18. Relation of dietary restraint scores to activation of reward-related brain regions in response to food intake, anticipated intake, and food pictures.

    PubMed

    Burger, Kyle S; Stice, Eric

    2011-03-01

    Prospective studies indicate that individuals with elevated dietary restraint scores are at increased risk for future bulimic symptom onset, suggesting that these individuals may show hyper-responsivity of reward regions to food and food cues. Thus, we used functional magnetic resonance imaging (fMRI) to examine the relation of dietary restraint scores to activation of reward-related brain regions in response to receipt and anticipated receipt of chocolate milkshake and exposure to pictures of appetizing foods in 39 female adolescents (mean age=15.5 ± 0.94). Dietary restraint scores were positively correlated with activation in the right orbitofrontal cortex (OFC) and bilateral dorsolateral prefrontal cortex (DLPFC) in response to milkshake receipt. However, dietary restraint scores did not correlate with activation in response to anticipated milkshake receipt or exposure to food pictures. Results indicate that individuals who report high dietary restraint have a hyper-responsivity in reward-related brain regions when food intake is occurring, which may increase risk for overeating and binge eating. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Lifelong physical activity affects mini mental state exam scores in individuals over 55 years of age.

    PubMed

    Nemati Karimooy, Habibollah; Hosseini, Mahmoud; Nemati, Maryam; Esmaily, Habib Ollah

    2012-04-01

    The positive effects of physical activity on cognition have been widely documented. Human studies and the results obtained from animal models of Alzheimer's disease (AD) have shown that if commenced early in life, exercise effectively reduces the development of cognitive deficits caused by aging. In the present study, the scores on Mini Mental State Exam (MMSE) of individuals over 55 years old who had a history of exercising have been compared to those without a history of exercising. This research was carried out on 273 individuals over 55 years of age. The subjects were randomly chosen from different areas of Mashhad and from exercise clubs. Each person completed a personal information form containing data such as demographics in addition to details of their involvement in sporting activity. Subjects were categorized as follows: 1- non-exercised, 2- exercised. The people in group 2 were then divided into non-professionally exercised (with a history of 2-10 years exercising) or professionally--exercised subjects (i.e. people who were currently, or had previously been members of an exercise club and/or had been trained for at least 10 years). Out of 273 subjects questioned in the present study, 229 were males and 44 were females. The MMSE score in men was significantly higher than women (p < 0.001). The exercised individuals of both sexes had significantly higher scores compared to non-exercised group (p < 0.001). There was no significant difference between professionally- exercised individuals of either sex in comparison with exercised ones. It is suggested that lifelong physical activity and exercise affects cognitive performance in old age. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Endoscopic Scores for Evaluation of Crohn's Disease Activity at Small Bowel Capsule Endoscopy: General Principles and Current Applications.

    PubMed

    Rosa, Bruno; Pinho, Rolando; de Ferro, Susana Mão; Almeida, Nuno; Cotter, José; Saraiva, Miguel Mascarenhas

    2016-01-01

    The small bowel is affected in the vast majority of patients with Crohn's Disease (CD). Small bowel capsule endoscopy (SBCE) has a very high sensitivity for the detection of CD-related pathology, including early mucosal lesions and/or those located in the proximal segments of the small bowel, which is a major advantage when compared with other small bowel imaging modalities. The recent guidelines of European Society of Gastrointestinal Endoscopy (ESGE) and European Crohn's and Colitis Organisation (ECCO) advocate the use of validated endoscopic scoring indices for the classification of inflammatory activity in patients with CD undergoing SBCE, such as the Lewis Score or the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). These scores aim to standardize the description of lesions and capsule endoscopy reports, contributing to increase inter-observer agreement and enabling a stratification of the severity of the disease. On behalf of the Grupo de Estudos Português do Intestino Delgado (GEPID) - Portuguese Small Bowel Study Group, we aimed to summarize the general principles and clinical applications of current endoscopic scoring systems for SBCE in the setting of CD, covering the topic of suspected CD as well as the evaluation of disease extent (with potential prognostic and therapeutic impact), evaluation of mucosal healing in response to treatment and evaluation of post-surgical recurrence in patients with previously established diagnosis of CD.

  1. Relationship between in vivo chlorzoxazone hydroxylation, hepatic cytochrome P450 2E1 content and liver injury in obese non-alcoholic fatty liver disease patients.

    PubMed

    Orellana, Myriam; Rodrigo, Ramón; Varela, Nelson; Araya, Julia; Poniachik, Jaime; Csendes, Attila; Smok, Gladys; Videla, Luis A

    2006-01-01

    The aim of the present study was to test the hypothesis that induction of cytochrome P450 2E1 (CYP2E1) in the liver of patients with non-alcoholic fatty liver disease (NAFLD) is correlated both with the in vivo activity of the cytochrome and with the development of liver injury. For this purpose, the liver content of CYP2E1 was determined by Western blot and the CYP2E1 activity by the in vivo hydroxylation of chlorzoxazone (CLZ). The study groups were obese women with an average body mass index (BMI) of 40.3kg/m(2), who underwent therapeutic gastroplasty or gastrectomy with a gastro-jejunal anastomosis. Further, the hepatic histology was determined to establish the pathological score grouping the subjects into three categories: control, steatosis and steatohepatitis. The liver CYP2E1 content and the CLZ hydroxylation of obese patients with steatosis and, particularly, with steatohepatitis were significantly higher than controls and correlated positively with both the severity of the liver damage. These data provide evidence that CYP2E1 would be involved in the mechanism of liver injury found in obese NAFLD patients. Also, the correlation between liver CYP2E1 content and in vivo CLZ hydroxylation would validate the latter as a reliable indicator of liver injury in NAFLD, thus providing a simple and not invasive method to study these patients.

  2. Validity and Reliability of Nintendo Wii Fit Balance Scores

    PubMed Central

    Wikstrom, Erik A.

    2012-01-01

    Context: Interactive gaming systems have the potential to help rehabilitate patients with musculoskeletal conditions. The Nintendo Wii Balance Board, which is part of the Wii Fit game, could be an effective tool to monitor progress during rehabilitation because the board and game can provide objective measures of balance. However, the validity and reliability of Wii Fit balance scores remain unknown. Objective: To determine the concurrent validity of balance scores produced by the Wii Fit game and the intrasession and intersession reliability of Wii Fit balance scores. Design: Descriptive laboratory study. Setting: Sports medicine research laboratory. Patients or Other Participants: Forty-five recreationally active participants (age  =  27.0 ± 9.8 years, height  =  170.9 ± 9.2 cm, mass  =  72.4 ± 11.8 kg) with a heterogeneous history of lower extremity injury. Intervention(s): Participants completed a single-limb–stance task on a force plate and the Star Excursion Balance Test (SEBT) during the first test session. Twelve Wii Fit balance activities were completed during 2 test sessions separated by 1 week. Main Outcome Measure(s): Postural sway in the anteroposterior (AP) and mediolateral (ML) directions and the AP, ML, and resultant center-of-pressure (COP) excursions were calculated from the single-limb stance. The normalized reach distance was recorded for the anterior, posteromedial, and posterolateral directions of the SEBT. Wii Fit balance scores that the game software generated also were recorded. Results: All 96 of the calculated correlation coefficients among Wii Fit activity outcomes and established balance outcomes were interpreted as poor (r < 0.50). Intrasession reliability for Wii Fit balance activity scores ranged from good (intraclass correlation coefficient [ICC]  =  0.80) to poor (ICC  =  0.39), with 8 activities having poor intrasession reliability. Similarly, 11 of the 12 Wii Fit balance activity scores demonstrated

  3. Risk factors for non-alcoholic fatty liver disease are common in patients with non-B non-C hepatocellular carcinoma in India.

    PubMed

    David, Deepu; Raghavendran, Anantharam; Goel, Ashish; Bharath Kumar, C; Kodiatte, Thomas Alex; Burad, Deepak; Abraham, Priya; Ramakrishna, Banumathi; Joseph, Philip; Ramachandran, Jeyamani; Eapen, C E

    2017-09-01

    The aim of the study was to analyze the prevalence of risk factors for non-alcoholic fatty liver disease (NAFLD) in patients with non-B non-C hepatocellular carcinoma (HCC). Between June 2012 and November 2014, patients with HCC, negative for hepatitis B surface antigen and hepatitis C virus antibody, were included in this study. All patients were assessed for risk factors for NAFLD such as diabetes mellitus (DM), hypertension, dyslipidemia, metabolic syndrome, and obesity. Forty-seven patients with non-B non-C HCC (males, 37; age, 60±10 years; mean±SD) were studied. Model for end-stage liver disease score was 11±4. Twenty-five patients were in Child's class A. History of significant alcohol intake was noted in 11 (23%) patients. Prevalence of risk factors for NAFLD were obesity 24 (51%), DM 22 (47%), metabolic syndrome 21 (45%), hypertension 16 (34%), and dyslipidemia 13 (28%). Forty (85%) patients had at least one risk factor for NAFLD. The mean duration of at least one NAFLD risk factor was 7.5 years, prior to diagnosis of HCC. Thirteen (28%) patients were positive for anti-HBc; however, none of the study patients had detectable HBV DNA in blood. Eighty-five percent of the patients with non-B non-C HCC had at least one risk factor for NAFLD. None of the study patients had occult hepatitis B infection. NAFLD is emerging as the major etiological contributing factor for non-B non-C HCC in India.

  4. Application of the combined FibroMeter vibration-controlled transient elastography algorithm in Chinese patients with non-alcoholic fatty liver disease.

    PubMed

    Loong, Thomson Chi-Wang; Wei, Jeremy Lok; Leung, Jonathan Chung-Fai; Wong, Grace Lai-Hung; Shu, Sally She-Ting; Chim, Angel Mei-Ling; Chan, Anthony Wing-Hung; Choi, Paul Cheung-Lung; Tse, Yee-Kit; Chan, Henry Lik-Yuen; Wong, Vincent Wai-Sun

    2017-07-01

    The FibroMeter vibration-controlled transient elastography (FM VCTE) is a new formula combining the serum test FM and liver stiffness measurement (LSM) by VCTE. We tested the accuracy and utility of FM VCTE for fibrosis staging in patients with non-alcoholic fatty liver disease (NAFLD). Two hundred fifteen NAFLD patients with LSM, FM NAFLD, FM VCTE, and other serum tests (aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, BARD score, NAFLD fibrosis score, and aspartate aminotransferase-to-alanine aminotransferase ratio) performed 1 day before liver biopsy were evaluated. Sixty-nine (32.1%) and 43 (20.0%) patients had F2-4 and F3-4, respectively. LSM had higher diagnostic accuracy (area under receiver-operating characteristics curves [AUROC] 0.851 for F2-4, 0.940 for F3-4; Obuchowski index 0.937 ± 0.007) than all evaluated serum tests, while FM NAFLD was the most accurate serum test (AUROC 0.775 and 0.774; Obuchowski index 0.891 ± 0.013). FM VCTE had similar accuracy to LSM (AUROC 0.855 and 0.901; Obuchowski index 0.927 ± 0.009). LSM had excellent negative predictive values of 92.4% and 99.2% to exclude F2-4 and F3-4, but the positive predictive values (PPV) were only 71.4% and 61.0%, respectively. In patients with high LSM, the use of FM VCTE improved the PPV from 71.4% to 84.4% for F2-4 and from 61.0% to 88.9% for F3-4. Liver biopsy could be spared in around 50-65% of patients. Liver stiffness measurement alone can confidently exclude significant and advanced fibrosis in NAFLD patients. Using FM VCTE in patients with high liver stiffness can increase the positive predictive value to rule in F2-4 and F3-4. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  5. Alcohol Use Among Active Duty Women: Analysis AUDIT Scores From the 2011 Health-Related Behavior Survey of Active Duty Military Personnel.

    PubMed

    Jeffery, Diana D; Mattiko, Mark

    2016-01-01

    Numerous studies document higher substance use among military men after deployment; similar studies focused on military women are limited. This study examines alcohol use of active duty women and deployment factors, social/environmental/attitudinal factors, and psychological/intrapersonal factors. Secondary data analysis of the 2011 Survey of Health-Related Behavior of active duty military personnel was conducted using bivariate statistics and multiple regression analyses with Alcohol Use Disorders Identification Test scores as the dependent variable. Nearly 94% had low risk for alcohol use disorders. Length of combat experience and extent of combat exposure were unrelated to Alcohol Use Disorders Identification Test scores; noncombat deployment was unrelated after controlling for marital status, age of first drink, pay grade, and branch of service. Significant motivators (p < 0.001) for drinking were "like/enjoy drinking," "drink to cheer up," "drink to forget problems," and significant deterrents were "cost of alcohol" and "fear of upsetting family/friends if used alcohol." Anger propensity, risk propensity, lifetime prevalence of suicidal ideation, and depressed mood were significant predictors in the regression model after controlling for covariates. Findings suggest that some active duty women use alcohol to cope with adverse emotional states, whereas others use alcohol consistent with propensity for high-risk behaviors. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  6. Cytolytic Activity Score to Assess Anticancer Immunity in Colorectal Cancer.

    PubMed

    Narayanan, Sumana; Kawaguchi, Tsutomu; Yan, Li; Peng, Xuan; Qi, Qianya; Takabe, Kazuaki

    2018-05-16

    Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA). CYT was defined by GZMA and PRF1 expression, and CIBERSORT was used to evaluate intratumoral immune cell composition. High CYT was associated with high microsatellite instability (MSI-H), as well as high levels of activated memory CD4+T cells, gamma-delta T cells, and M1 macrophages. CYT-high CRC patients had improved overall survival (p = 0.019) and disease-free survival (p = 0.016) compared with CYT-low CRC patients, especially in TIL-positive tumors. Multivariate analysis demonstrated that CYT- high associates with improved survival independently after controlling for age, lymphovascular invasion, colonic location, microsatellite instability, and TIL positivity. The levels of immune checkpoint molecules (ICMs)-programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), T cell immunoglobulin and mucin domain 3 (TIM3), and indoleamine 2,3-dioxygenase 1 (IDO1)-correlated significantly with CYT (p < 0.0001); with improved survival in CYT-high and ICM-low patients, and poorer survival in ICM-high patients. High CYT within CRC is associated with improved survival, likely due to increased immunity and cytolytic activity of T cells and M1 macrophages. High CYT is also associated with high expression of ICMs; thus, further studies to elucidate the role of CYT as a predictive biomarker of the efficacy of immune checkpoint blockade are warranted.

  7. DRAGON score predicts functional outcomes in acute ischemic stroke patients receiving both intravenous tissue plasminogen activator and endovascular therapy.

    PubMed

    Wang, Arthur; Pednekar, Noorie; Lehrer, Rachel; Todo, Akira; Sahni, Ramandeep; Marks, Stephen; Stiefel, Michael F

    2017-01-01

    The DRAGON score, which includes clinical and computed tomographic (CT) scan parameters, predicts functional outcomes in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). We assessed the utility of the DRAGON score in predicting functional outcome in stroke patients receiving both IV tPA and endovascular therapy. A retrospective chart review of patients treated at our institution from February 2009 to October 2015 was conducted. All patients with computed tomography angiography (CTA) proven large vessel occlusions (LVO) who underwent intravenous thrombolysis and endovascular therapy were included. Baseline DRAGON scores and modified Rankin Score (mRS) at the time of hospital discharge was calculated. Good outcome was defined as mRS ≤3. Fifty-eight patients with LVO of the anterior circulation were studied. The mean DRAGON score of patients on admission was 5.3 (range, 3-8). All patients received IV tPA and endovascular therapy. Multivariate analysis demonstrated that DRAGON scores ≥7 was associated with higher mRS ( P < 0.006) and higher mortality ( P < 0.0001) compared with DRAGON scores ≤6. Patients with DRAGON scores of 7 and 8 on admission had a mortality rate of 3.8% and 40%, respectively. The DRAGON score can help predict better functional outcomes in ischemic stroke patients receiving both IV tPA and endovascular therapy. This data supports the use of the DRAGON score in selecting patients who could potentially benefit from more invasive therapies such as endovascular treatment. Larger prospective studies are warranted to further validate these results.

  8. The polymyalgia rheumatica activity score in daily use: proposal for a definition of remission.

    PubMed

    Leeb, Burkhard F; Rintelen, Bernhard; Sautner, Judith; Fassl, Christian; Bird, Howard A

    2007-06-15

    To confirm the reliability and applicability of the Polymyalgia Rheumatica Disease Activity Score (PMR-AS), and to establish a threshold for remission. First, 78 patients with PMR (50 women/28 men, mean age 65.97 years) were enrolled in a cross-sectional evaluation. The PMR-AS, patient's satisfaction with disease status (PATSAT; range 1-5), erythrocyte sedimentation rate (ESR; first hour), and a visual analog scale of patients' general health assessment (VAS patient global; range 0-100) were recorded. Subsequently, another 39 PMR patients (24 women/15 men, mean age 68.12 years) were followed longitudinally. Relationships between the PMR-AS, PATSAT, ESR, and VAS patient global were analyzed by the Kruskal-Wallis test, Spearman's rank correlation, and kappa statistics. PMR-AS values in patients with a PATSAT score of 1 and a VAS patient global <10 formed the basis to establish a remission threshold. PMR-AS values were significantly related to PATSAT (P < 0.001), VAS patient global (P < 0.001), and ESR (P < 0.01). PATSAT and VAS patient global were reasonably different (kappa = 0.226). The median PMR-AS score in patients with PATSAT score 1 and VAS patient global <10 was 0.7 (range 0-3.3), and the respective 75th percentile was 1.3. To enhance applicability, a range from 0 to 1.5 was proposed to define remission in PMR. The median ESR in these patients was 10 mm/hour (range 3-28), indicating external validity. We demonstrated the reliability, validity, and applicability of the PMR-AS in daily routine. Moreover, we proposed a remission threshold (0-1.5) founded on patient-dependent parameters.

  9. Optimal responses in disease activity scores to treatment in rheumatoid arthritis: Is a DAS28 reduction of >1.2 sufficient?

    PubMed

    Mian, Aneela N; Ibrahim, Fowzia; Scott, David L; Galloway, James

    2016-06-16

    The overall benefit of intensive treatment strategies in rheumatoid arthritis (RA) remains uncertain. We explored how reductions in disability and improvements in quality of life scores are affected by alternative assessments of reductions in disease activity scores for 28 joints (DAS28) in two trials of intensive treatment strategies in active RA. One trial (CARDERA) studied 467 patients with early active RA receiving 24 months of methotrexate monotherapy or steroid and disease-modifying anti-rheumatic drug (DMARD) combinations. The other trial (TACIT) studied 205 patients with established active RA; they received 12 months of treatment with DMARD combinations or biologic agents. We compared changes in the health assessment questionnaire (HAQ) and Euroqol-5D (EQ5D) at trial endpoints in European League Against Rheumatism (EULAR) good and moderate EULAR responders in patients in whom complete endpoint data were available. In the CARDERA trial 98 patients (26 %) were good EULAR responders and 160 (32 %) were EULAR moderate responders; comparable data in TACIT were 66 (35 %) and 86 (46 %) patients. The magnitude of change in the HAQ and EQ5D was greater in both trials in EULAR good responders than in EULAR moderate responders. HAQ scores had a difference in of -0.49 (95 % CI -0.66, -0.32) in the CARDERA and -0.31 (95 % CI -0.47, -0.13) in the TACIT trial. With the EQ5D comparable differences were 0.12 (95 % CI 0.04, 0.19) and 0.15 (95 % CI 0.05, 0.25). Both exceeded minimum clinically important differences in HAQ and EQ5D scores. We conclude that achieving a good EULAR response with DMARDs and biologic agents in active RA results in substantially improved mean HAQ and EQ5D scores. Patients who achieve such responses should continue on treatment. However, continuing such treatment strategies is more challenging when only a moderate EULAR response is achieved. In these patients evidence of additional clinically important benefits in measures such as the HAQ

  10. TS-Chemscore, a Target-Specific Scoring Function, Significantly Improves the Performance of Scoring in Virtual Screening.

    PubMed

    Wang, Wen-Jing; Huang, Qi; Zou, Jun; Li, Lin-Li; Yang, Sheng-Yong

    2015-07-01

    Most of the scoring functions currently used in structure-based drug design belong to 'universal' scoring functions, which often give a poor correlation between the calculated scores and experimental binding affinities. In this investigation, we proposed a simple strategy to construct target-specific scoring functions based on known 'universal' scoring functions. This strategy was applied to Chemscore, a widely used empirical scoring function, which led to a new scoring function, termed TS-Chemscore. TS-Chemscore was validated on 14 protein targets, which cover a wide range of biological target categories. The results showed that TS-Chemscore significantly improved the correlation between the calculated scores and experimental binding affinities compared with the original Chemscore. TS-Chemscore was then applied in virtual screening to retrieve novel JAK3 and YopH inhibitors. Top 30 compounds for each target were selected for experimental validation. Six active compounds for JAK3 and four for YopH were obtained. These compounds were out of the lists of top 30 compounds sorted by Chemscore. Collectively, TS-Chemscore established in this study showed a better performance in virtual screening than its counterpart Chemscore. © 2014 John Wiley & Sons A/S.

  11. Tomato powder inhibits hepatic steatosis and inflammation potentially through restoring SIRT1 activity and adiponectin function independent of carotenoid cleavage enzymes in mice

    USDA-ARS?s Scientific Manuscript database

    Scope: Beta-carotene-15,15'-oxygenase (BCO1) and beta-carotene-9',10'-oxygenase (BCO2) metabolize lycopene to biologically active metabolites, which can ameliorate nonalcoholic fatty liver disease (NAFLD). We investigated the effects of tomato powder (TP), a whole food containing substantial lycopen...

  12. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

    PubMed

    Loguercio, Carmela; Andreone, Pietro; Brisc, Ciprian; Brisc, Michaela Cristina; Bugianesi, Elisabetta; Chiaramonte, Maria; Cursaro, Carmela; Danila, Mirela; de Sio, Ilario; Floreani, Annarosa; Freni, Maria Antonietta; Grieco, Antonio; Groppo, Marzia; Lazzari, Roberta; Lobello, Salvatore; Lorefice, Elisabetta; Margotti, Marzia; Miele, Luca; Milani, Stefano; Okolicsanyi, Lajos; Palasciano, Giuseppe; Portincasa, Piero; Saltarelli, Patrizia; Smedile, Antonina; Somalvico, Francesco; Spadaro, Aldo; Sporea, Ioan; Sorrentino, Paolo; Vecchione, Raffaela; Tuccillo, Concetta; Del Vecchio Blanco, Camillo; Federico, Alessandro

    2012-05-01

    The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe.

    PubMed

    Simon, Tracey G; Corey, Kathleen E; Cannon, Christopher P; Blazing, Michael; Park, Jeong-Gun; O'Donoghue, Michelle L; Chung, Raymond T; Giugliano, Robert P

    2018-05-26

    The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of unique metabolic risk indicators that may accurately predict residual cardiovascular (CV) risk in patients with established coronary disease and metabolic dysfunction. We applied the NFS prospectively to 14,819 post-ACS patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), in the IMPROVE-IT trial, using validated NFS cutoffs. The primary endpoint included CV death, myocardial infarction, unstable angina, revascularization or stroke. Outcomes were compared between NFS categories and treatment arms using frequency of events, KM rates and adjusted Cox proportional hazard models. The ability of the NFS to predict recurrent CV events was independently validated in 5395 placebo-treated patients enrolled in the SOLID-TIMI 52 trial. Among 14,819 patients enrolled in IMPROVE-IT, 14.2% (N = 2106) were high-risk (NFS > 0.67). The high-risk group had a 30% increased risk of recurrent major CV events, compared to the low-risk NFS group (HR 1.30 [1.19-1.43]; p < 0.001). Among high-risk patients, ezetimibe/simvastatin conferred a 3.7% absolute reduction in risk of recurrent CV events, compared to placebo/simvastatin (HR 0.85 [0.74-0.98]), translating to a number-needed-to-treat of 27. Similar benefit was not found in the low-risk group (HR ezetimibe/simvastatin vs. placebo/simvastatin, 1.01 [0.91-1.12]; p-interaction = 0.053). The relationship between NFS category and recurrent CV events was independently validated in patients enrolled in SOLID-TIMI 52 (HR for NFS > 0.67 vs. NFS < -1.455 = 1.55 [1.32-1.81]; p < 0.001). Stratification of cardiovascular risk by NFS identifies an independent population of patients who are at highest risk of recurrent events, and most likely to benefit from dual lipid-lowering therapy. Clinical trials.gov: NCT00202878. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Increased risk of nonalcoholic fatty liver disease with occupational stress in Chinese policemen

    PubMed Central

    Li, Chen; Xing, Jing-Jing; Shan, An-Qi; Leng, Ling; Liu, Jin-Chuan; Yue, Song; Yu, Hao; Chen, Xi; Tian, Feng-Shi; Tang, Nai-Jun

    2016-01-01

    Abstract Nonalcoholic fatty liver disease (NAFLD) and occupational stress have been recognized as major public health concerns. We aimed to explore whether occupational stress was associated with NAFLD in a police population. A total of 6559 male police officers were recruited for this prospective study in April 2007. Among them, 2367 eligible subjects participated in follow-up from 2008 to 2011. NAFLD was diagnosed based on standard criteria. Occupational stress was evaluated by Occupational Stress Inventory-Revised scores. The incidence of NAFLD was 31.2% in the entire police. After adjusting for traditional risk factors, moderate occupational stress (MOS), high occupational stress (HOS), and high personal strain (HPS) were risk factors (MOS: hazard ratio [HR] = 1.237, 95% confidence interval [CI] = 1.049–1.460; HOS: HR = 1.727, 95% CI = 1.405–2.124; HPS: HR = 3.602, 95% CI = 1.912–6.787); and low occupational stress (LOS) and low personal strain (LPS) were protective factors (LOS: HR = 0.366, 95% CI = 0.173–0.776; LPS: HR = 0.490, 95% CI = 0.262–0.919) for NAFLD in the entire police cohort. HOS and HPS remained robust among traffic police. HOS and HPS were independent predictors for the development of NAFLD in a Chinese police population. Additional future prospective investigations are warranted to validate our findings. PMID:27861366

  15. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance

    PubMed Central

    Stål, Per

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD. PMID:26494963

  16. The Relation between Factor Score Estimates, Image Scores, and Principal Component Scores

    ERIC Educational Resources Information Center

    Velicer, Wayne F.

    1976-01-01

    Investigates the relation between factor score estimates, principal component scores, and image scores. The three methods compared are maximum likelihood factor analysis, principal component analysis, and a variant of rescaled image analysis. (RC)

  17. Hepatic AMP Kinase as a Potential Target for Treating Nonalcoholic Fatty Liver Disease: Evidence from Studies of Natural Products.

    PubMed

    Xu, Gang; Huang, Kaixun; Zhou, Jun

    2018-01-01

    Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is the leading cause of cryptogenic cirrhosis and has consistently been implicated in related metabolic disorders, such as dyslipidemia and type 2 diabetes (T2D). However, the pathogenesis of NAFLD remains to be elucidated, and no established therapeutic regimens for treating NAFLD exist. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), the main cellular energy sensor, has been implicated as a key regulator of hepatic lipid and glucose metabolism. Recently, emerging evidence indicates that many plant-derived natural products are capable of ameliorating NAFLD by targeting AMPK. The published literature in PubMed relating to this topic was searched through June 2016. Significant advances have been made with respect to understanding the protective effects of plant-derived natural products against NAFLD. A variety of natural products, including alkaloids (berberine, demethyleneberberine, nicotine, caffeine, etc.), polyphenols (resveratrol, puerarin, curcumin, caffeic acid, etc.) and other compounds (β- caryophyllene, gastrodin, compound K, betulinic acid, etc.), have demonstrated promising results in preclinical studies. Mechanistic studies of these compounds have focused on their activation of AMPK and its downstream effectors involved in lipid metabolism. The findings of this review confirm that plant-derived natural products capable of activating the AMPK signaling pathway are potential therapeutic agents for NAFLD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Mechanistically linked serum miRNAs distinguish between drug induced and fatty liver disease of different grades.

    PubMed

    Liu, Zhichao; Wang, Yuping; Borlak, Jürgen; Tong, Weida

    2016-04-05

    Hepatic steatosis is characterised by excessive triglyceride accumulation in the form of lipid droplets (LD); however, mechanisms differ in drug induced (DIS) and/or non-alcoholic fatty liver disease (NAFLD). Here we hypothesized distinct molecular circuits of microRNA/LD-associated target genes and searched for mechanistically linked serum and tissue biomarkers that would distinguish between DIS and human NAFLD of different grades. We analysed >800 rat hepatic whole genome data for 17 steatotic drugs and identified 157 distinct miRNAs targeting 77 DIS regulated genes. Subsequently, genomic data of N = 105 cases of human NAFLD and N = 32 healthy controls were compared to serum miRNA profiles of N = 167 NAFLD patients. This revealed N = 195 tissue-specific miRNAs being mechanistically linked to LD-coding genes and 24 and 9 miRNAs were commonly regulated in serum and tissue of advanced and mild NAFLD, respectively. The NASH serum regulated miRNAs informed on hepatic inflammation, adipocytokine and insulin signalling, ER-and caveolae associated activities and altered glycerolipid metabolism. Conversely, serum miRNAs associated with blunt steatosis specifically highlighted activity of FOXO1&HNF4α on CPT2, the lipid droplet and ER-lipid-raft associated PLIN3 and Erlin1. Altogether, serum miRNAs informed on the molecular pathophysiology of NAFLD and permitted differentiation between DIS and NAFLD of different grades.

  19. Using the CDC's Worksite Health ScoreCard as a Framework to Examine Worksite Health Promotion and Physical Activity.

    PubMed

    Gutermuth, Leah K; Hager, Erin R; Pollack Porter, Keshia

    2018-06-21

    Worksite health promotion programs are emerging as an effective approach for addressing the adult obesity epidemic and improving the overall health of employees. We conducted a scoping review to identify articles that described a physical activity component (eg, promoted increased physical or reduced sitting time) of a worksite health promotion intervention. Our search specified full-length articles published in English from January 2000 through July 2015. We used the Centers for Disease Control and Prevention's Worksite Health ScoreCard, a validated tool, as a framework to summarize information on organizational supports strategies (18 questions) and physical activity strategies (9 questions) implemented by worksite health promotion programs. We also determined whether or not the included studies reported significant (P < .05) improvements in physical activity. We identified 18 worksite health promotion programs; 11 produced significant improvements in physical activity. Incentives, health risk assessments, health promotion committees, leadership support, marketing, and subsidies or discounts for use of exercise facilities were the most effective organizational supports strategies cited, and physical activity seminars, classes, and workshops were the most effective physical activity strategies cited. The use of the Health ScoreCard allowed for a practical interpretation of our findings, which can inform next steps for the field. Future research should explore the relationships between components of worksite health promotion programs and their outcomes to further develop best practices that can improve worker health and promote physical activity.

  20. Non-alcoholic fatty liver disease in diabetics--prevalence and predictive factors in a multiracial hospital clinic population in Malaysia.

    PubMed

    Chan, Wah-Kheong; Tan, Alexander Tong-Boon; Vethakkan, Shireene Ratna; Tah, Pei-Chien; Vijayananthan, Anushya; Goh, Khean-Lee

    2013-08-01

    There is currently no published study comparing prevalence of non-alcoholic fatty liver disease (NAFLD) and associated factors among diabetics of different ethnicity in the Asia-Pacific region. Cross-sectional study of consecutive patients in the Diabetic Clinic in University of Malaya Medical Centre. The Global Physical Activity Questionnaire and a semiquantitative food-frequency questionnaire were used to assess physical activity and dietary intake, respectively. Diagnosis of NAFLD was ultrasound-based and following exclusion of significant alcohol intake. Data for 399 patients were analyzed (mean age 62.3 ± 10.5 years, 43.1% men). The racial distribution was Chinese 43.6%, Indian 33.1%, Malay 22.3%, and others 1.0%. The prevalence of NAFLD was 49.6%. On univariate analysis, factors associated with NAFLD were age < 65 years, race, obesity, central obesity, glycated hemoglobin ≥ 7.0%, and elevated serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase levels. Patients with low physical activity were more likely to have NAFLD (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.06-2.63, P = 0.020). The prevalence of NAFLD was highest among Malays (60.7%), followed by Indians (51.5%), and lowest among Chinese (42.0%) consistent with higher prevalence of central obesity and higher percentage calorie intake from fat in the former groups of patients. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR = 2.20, 95% CI = 1.29-3.75, P = 0.004) and elevated serum ALT level (OR = 1.98, 95% CI = 1.21-3.25, P = 0.007). NAFLD was seen in half of a cohort of diabetic patients and was independently associated with central obesity and elevated serum ALT level. Prevalence of NAFLD was different and paralleled the difference in prevalence of central obesity and in percentage calorie intake from fat among the different ethnic groups. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia

  1. MR Enterography Assessment of Bowel Inflammation Severity in Crohn Disease Using the MR Index of Activity Score: Modifying Roles of DWI and Effects of Contrast Phases.

    PubMed

    Kim, Jin Sil; Jang, Hye Young; Park, Seong Ho; Kim, Kyung-Jo; Han, Kyunghwa; Yang, Suk-Kyun; Ye, Byong Duk; Park, Sang Hyoung; Lee, Jong Seok; Kim, Hyun Jin

    2017-05-01

    The purpose of this article is to appraise the use of the MR index of activity (MaRIA) score in evaluating Crohn disease (CD) on present-day MR enterography images, with an emphasis on determining the modifying roles of DWI and the effects of different contrast enhancement phases. Fifty patients prospectively underwent MR enterography, including DWI and enteric and portal phase scans, and ileocolonoscopy with segmental CD endoscopic index of severity (CDEIS) scoring within a week. Thirty-nine terminal ilea and 40 right-sided colons (mean [± SD] segmental CDEIS score, 14.3 ± 12.1) from 42 patients with CD (mean age, 27 ± 6.2 years) were finally analyzed by three independent readers. Original and modified (ulcer replaced with DWI grade) MaRIA scores were compared regarding their correlation with segmental CDEIS score, accuracy in diagnosing active (segmental CDEIS score ≥ 3) and severe (segmental CDEIS score ≥ 12) inflammation, and interobserver reproducibility. The primary analysis used portal phase data, and the agreement between portal and enteric phase scores was analyzed. MaRIA and modified MaRIA scores correlated similarly with CDEIS scores (r = 0.737 and 0.742; p = 0.387) and did not significantly differ in terms of AUC values for the diagnosis of active (0.909 and 0.903; p = 0.571) or severe (0.907 and 0.892; p = 0.443) inflammation. The intraclass correlation coefficient was significantly higher for modified MaRIA than for MaRIA (0.845 and 0.701; p < 0.001). The mean difference between portal and enteric phase scores (i.e., portal minus enteric) was 0.33-0.36 score points for individual readers, and the Bland-Altman repeatability coefficient was 0.9-1.42 score points. Interobserver reproducibility in evaluating the severity of bowel inflammation in CD using the MaRIA score can be improved by modification with DWI. MaRIA scoring provides steady results across enteric and portal phases.

  2. Theacrine protects against nonalcoholic fatty liver disease by regulating acylcarnitine metabolism.

    PubMed

    Wang, Guo-En; Li, Yi-Fang; Zhai, Yu-Jia; Gong, Lian; Tian, Jing-Yu; Hong, Mo; Yao, Nan; Wu, Yan-Ping; Kurihara, Hiroshi; He, Rong-Rong

    2018-05-01

    Acylcarnitine metabolism disorder contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). There are, however, few ideal medications for NAFLD, which work by targeting acylcarnitine metabolism. The aim of this study was to investigate the protective effects of theacrine, a rare purine alkaloid isolated from Camellia assamica var. kucha, against acylcarnitine metabolism disorder in NAFLD. The pharmacological activities of theacrine were studied using high-fat diet (HFD)-fed ApoE-/- and C57BL/6 J mice models. Oleate-treated HepG2 and L-02 cells were used to investigate the molecular mechanism of theacrine on acylcarnitine metabolism. The target of theacrine was confirmed in vitro as the blockade of sirtuin 3 (SIRT3) and protein kinase A. Theacrine inhibits hepatic steatosis and liver inflammation and improves energy expenditure in HFD-fed mice. Theacrine ameliorates acylcarnitine metabolism disorder in HFD-fed mice and oleate-treated hepatocytes by improving fatty acid oxidation. The underlying mechanism involves theacrine's activation of the mitochondrial deacetylase SIRT3 and consequently, the increased activity of long-chain acyl coenzyme A dehydrogenase (LCAD) through deacetylation. Theacrine promotes acylcarnitine metabolism in NAFLD through the SIRT3/LCAD signaling pathway. The target of theacrine's activities on NAFLD is identified as SIRT3. Copyright © 2018. Published by Elsevier Inc.

  3. Ultrasound-detected subclinical inflammation was better reflected by the disease activity score (DAS-28) in patients with suspicion of inflammatory arthritis compared to established rheumatoid arthritis.

    PubMed

    Ciurtin, Coziana; Wyszynski, Karol; Clarke, Robert; Mouyis, Maria; Manson, Jessica; Marra, Giampiero

    2016-10-01

    Limited data are available about the ultrasound (US)-detected inflammatory features in patients with suspicion of inflammatory arthritis (S-IA) vs. established rheumatoid arthritis (RA). Our study aimed to assess if the presence of power Doppler (PD) can be predicted by a combination of clinical, laboratory and US parameters. We conducted a real-life, retrospective cohort study comparing clinical, laboratory and US parameters of 108 patients with established RA and 93 patients with S-IA. We propose a PD signal prediction model based on a beta-binomial distribution for PD variable using a mix of outcome measures. Patients with RA in clinical remission had significantly more active inflammation and erosions on US when compared with patients with S-IA with similar disease scores (p = 0.03 and p = 0.01, respectively); however, RA patients with different disease activity score (DAS-28) scores had similar PD scores (p = 0.058). The PD scores did not correlate with erosions (p = 0.38) or DAS-28 scores (p = 0.28) in RA patients, but they correlated with high disease activity in S-IA patients (p = 0.048). Subclinical inflammation is more common in patients with RA in clinical remission or with low disease activity than in patients with S-IA; therefore, US was more useful in assessing for true remission in RA rather than diagnosing IA in patients with low disease activity scores. This is the first study to propose a PD prediction model integrating several outcome measures in the two different groups of patients. Further research into validating this model can minimise the risk of underdiagnosing subclinical inflammation.

  4. Validation of the REMA score for predicting mast cell clonality and systemic mastocytosis in patients with systemic mast cell activation symptoms.

    PubMed

    Alvarez-Twose, I; González-de-Olano, D; Sánchez-Muñoz, L; Matito, A; Jara-Acevedo, M; Teodosio, C; García-Montero, A; Morgado, J M; Orfao, A; Escribano, L

    2012-01-01

    A variable percentage of patients with systemic mast cell (MC) activation symptoms meet criteria for systemic mastocytosis (SM). We prospectively evaluated the clinical utility of the REMA score versus serum baseline tryptase (sBt) levels for predicting MC clonality and SM in 158 patients with systemic MC activation symptoms in the absence of mastocytosis in the skin (MIS). World Health Organization criteria for SM were applied in all cases. MC clonality was defined as the presence of KIT-mutated MC or by a clonal HUMARA test. The REMA score consisted of the assignment of positive or negative points as follows: male (+1), female (-1), sBt <15 μg/l (-1) or >25 μg/l (+2), presence (-2) or absence (+1) of pruritus, hives or angioedema and presence (+3) of presyncope or syncope. Efficiency of the REMA score for predicting MC clonality and SM was assessed by receiver operating characteristic (ROC) curve analyses and compared to those obtained by means of sBt levels alone. Molecular studies revealed the presence of clonal MC in 68/80 SM cases and in 11/78 patients who did not meet the criteria for SM. ROC curve analyses confirmed the greater sensitivity and a similar specificity of the REMA score versus sBt levels (84 vs. 59% and 74 vs. 70% for MC clonality and 87 vs. 62% and 73 vs. 71% for SM, respectively). Our results confirm the clinical utility of the REMA score to predict MC clonality and SM in patients suffering from systemic MC activation symptoms without MIS. Copyright © 2011 S. Karger AG, Basel.

  5. Atorvastatin reduces lipid accumulation in the liver by activating protein kinase A-mediated phosphorylation of perilipin 5.

    PubMed

    Gao, Xing; Nan, Yang; Zhao, Yuanlin; Yuan, Yuan; Ren, Bincheng; Sun, Chao; Cao, Kaiyu; Yu, Ming; Feng, Xuyang; Ye, Jing

    2017-12-01

    Statins have been proven to be effective in treating non-alcoholic fatty liver disease (NAFLD). Recently, it was reported that statins decreased the hepatic expression of perilipin 5 (Plin5), a lipid droplet (LD)-associated protein, which plays critical roles in regulating lipid accumulation and lipolysis in liver. However, the function and regulation mechanism of Plin5 have not yet been well-established in NAFLD treatment with statins. In this study, we observed that atorvastatin moderately reduced the expression of Plin5 in livers without changing the protein level of Plin5 in the hepatic LD fraction of mice fed with high-fat diet (HFD). Intriguingly, atorvastatin stimulated the PKA-mediated phosphorylation of Plin5 and reduced the triglyceride (TG) accumulation in hepatocytes with overexpression of wide type (Plin5-WT) compared to serine-155 mutant Plin5 (Plin5-S155A). Moreover, PKA-stimulated FA release of purified LDs carrying Plin5-WT but not Plin5-S155A. Glucagon, a PKA activator, stimulated the phosphorylation of Plin5-WT and inhibited its interaction with CGI-58. The results indicated that atorvastatin promoted lipolysis and reduced TG accumulation in the liver by increasing PKA-mediated phosphorylation of Plin5. This new mechanism of lipid-lowering effects of atorvastatin might provide a new strategy for NAFLD treatment. Copyright © 2017. Published by Elsevier B.V.

  6. Sirtuin 3 (SIRT3) Regulates α-Smooth Muscle Actin (α-SMA) Production through the Succinate Dehydrogenase-G Protein-coupled Receptor 91 (GPR91) Pathway in Hepatic Stellate Cells*

    PubMed Central

    Li, Ying Hui; Choi, Dae Hee; Lee, Eun Hye; Seo, Su Ryeon; Lee, Seungkoo

    2016-01-01

    Sirtuin 3 (SIRT3) is an NAD+-dependent protein deacetylase. Recent studies have shown that SIRT3 expression is decreased in nonalcoholic fatty liver disease (NAFLD). Moreover, SIRT3 is a key regulator of succinate dehydrogenase (SDH), which catalyzes the oxidation of succinate to fumarate. Increased succinate concentrations and the specific G protein-coupled receptor 91 (GPR91) are involved in the activation of hepatic stellate cells (HSCs). In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD. Our goal was also to determine whether succinate released from hepatocytes regulated HSC activation. Inhibiting SIRT3 using SIRT3 siRNA exacerbated HSC activation via the SDH-succinate-GPR91 pathway, and SIRT3 overexpression or honokiol treatment attenuated HSC activation in vitro. In isolated liver and HSCs from methionine- and choline-deficient (MCD) diet-induced NAFLD, the expression of SIRT3 and SDH activity was decreased, and the succinate concentrations and GPR91 expression were increased. Moreover, we found that GPR91 knockdown or resveratrol treatment improved the steatosis in MCD diet-fed mice. This investigation revealed a novel mechanism of the SIRT3-SDH-GPR91 cascade in MCD diet-induced HSC activation in NAFLD. These findings highlight the biological significance of novel strategies aimed at targeting SIRT3 and GPR91 in HSCs with the goal of improving NAFLD treatment. PMID:26912655

  7. Carbohydrate intake and nonalcoholic fatty liver disease: fructose as a weapon of mass destruction

    PubMed Central

    Basaranoglu, Gokcen; Bugianesi, Elisabetta

    2015-01-01

    Excessive accumulation of triglycerides (TG) in liver, in the absence of significant alcohol consumption is nonalcoholic fatty liver disease (NAFLD). NAFLD is a significant risk factor for developing cirrhosis and an independent predictor of cardiovascular disease. High fructose corn syrup (HFCS)-containing beverages were associated with metabolic abnormalities, and contributed to the development of NAFLD in human trials. Ingested carbohydrates are a major stimulus for hepatic de novo lipogenesis (DNL) and are more likely to directly contribute to NAFLD than dietary fat. Substrates used for the synthesis of newly made fatty acids by DNL are primarily glucose, fructose, and amino acids. Epidemiological studies linked HFCS consumption to the severity of fibrosis in patients with NAFLD. New animal studies provided additional evidence on the role of carbohydrate-induced DNL and the gut microbiome in NAFLD. The excessive consumption of HFCS-55 increased endoplasmic reticulum stress, activated the stress-related kinase, caused mitochondrial dysfunction, and increased apoptotic activity in the liver. A link between dietary fructose intake, increased hepatic glucose transporter type-5 (Glut5) (fructose transporter) gene expression and hepatic lipid peroxidation, MyD88, TNF-α levels, gut-derived endotoxemia, toll-like receptor-4, and NAFLD was reported. The lipogenic and proinflammatory effects of fructose appear to be due to transient ATP depletion by its rapid phosphorylation within the cell and from its ability to raise intracellular and serum uric acid levels. However, large prospective studies that evaluated the relationship between fructose and NAFLD were not performed yet. PMID:26005677

  8. Positive and negative symptom scores are correlated with activation in different brain regions during facial emotion perception in schizophrenia patients: a voxel-based sLORETA source activity study.

    PubMed

    Kim, Do-Won; Kim, Han-Sung; Lee, Seung-Hwan; Im, Chang-Hwan

    2013-12-01

    Schizophrenia is one of the most devastating of all mental illnesses, and has dimensional characteristics that include both positive and negative symptoms. One problem reported in schizophrenia patients is that they tend to show deficits in face emotion processing, on which negative symptoms are thought to have stronger influence. In this study, four event-related potential (ERP) components (P100, N170, N250, and P300) and their source activities were analyzed using EEG data acquired from 23 schizophrenia patients while they were presented with facial emotion picture stimuli. Correlations between positive and negative syndrome scale (PANSS) scores and source activations during facial emotion processing were calculated to identify the brain areas affected by symptom scores. Our analysis demonstrates that PANSS positive scores are negatively correlated with major areas of the left temporal lobule for early ERP components (P100, N170) and with the right middle frontal lobule for a later component (N250), which indicates that positive symptoms affect both early face processing and facial emotion processing. On the other hand, PANSS negative scores are negatively correlated with several clustered regions, including the left fusiform gyrus (at P100), most of which are not overlapped with regions showing correlations with PANSS positive scores. Our results suggest that positive and negative symptoms affect independent brain regions during facial emotion processing, which may help to explain the heterogeneous characteristics of schizophrenia. © 2013 Elsevier B.V. All rights reserved.

  9. An extra virgin olive oil rich diet intervention ameliorates the nonalcoholic steatohepatitis induced by a high-fat "Western-type" diet in mice.

    PubMed

    Jurado-Ruiz, Enrique; Varela, Lourdes M; Luque, Amparo; Berná, Genoveva; Cahuana, Gladys; Martinez-Force, Enrique; Gallego-Durán, Rocío; Soria, Bernat; de Roos, Baukje; Romero Gómez, Manuel; Martín, Franz

    2017-03-01

    We evaluated the protective effect of extra virgin olive oil (EVOO) in high-fat diets (HFDs) on the inflammatory response and liver damage in a nonalcoholic fatty liver disease (NAFLD) mouse model. C57BL/6J mice were fed a standard diet or a lard-based HFD (HFD-L) for 12 wk to develop NAFLD. HFD-fed mice were then divided into four groups and fed for 24 wk with the following: HFD-L, HFD-EVOO, HFD based on phenolics-rich EVOO, and reversion (standard diet). HFD-L-induced metabolic disorders were alleviated by replacement of lard with EVOO. EVOO diets improved plasma lipid profile and reduced body weight, plasma and epididymal fat INF-γ, IL-6 and leptin levels, and macrophage infiltration. Moreover, NAFLD activity scores were reduced. The liver lipid composition showed an increase in MUFAs, especially oleic acid, and a decrease in saturated fatty acids. Hepatic adiponutrin and Cd36 gene expression was upregulated in the EVOO groups. Liver ingenuity pathway analysis revealed in EVOO groups regulation of proteins involved in lipid metabolism, small molecule biochemistry, gastrointestinal disease, and liver regeneration. Dietary EVOO could repair HFD-induced hepatic damage, possibly via an anti-inflammatory effect in adipose tissue and modifications in the liver lipid composition and signaling pathways. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Somatotropic Axis Dysfunction in Non-Alcoholic Fatty Liver Disease: Beneficial Hepatic and Systemic Effects of Hormone Supplementation

    PubMed Central

    Cabrera, Daniel; Solís, Nancy; San Martín, Diego; Cofré, Catalina; Pizarro, Margarita; Abrigo, Johanna; Campos, Fabián; Irigoyen, Betzabé; Carrasco-Avino, Gonzalo; Bezares, Katiuska; Riquelme, Valentina; Riquelme, Arnoldo; Arrese, Marco; Barrera, Francisco

    2018-01-01

    Background: Somatotropic axis dysfunction associated with non-alcoholic fatty liver disease (NAFLD) has potential multisystemic detrimental effects. Here, we analysed the effects of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) supplementation on liver histology, adipokine profile and muscle function in an NAFLD model. Methods: C57BL/6 mice were fed with a high fat diet (HFD) for 12 weeks and were separated into three groups treated for 4 weeks with: (1) High fat diet (HFD) (n = 10); (2) HFD + GH 9 μg/g/d (n = 10); (3) HFD + IGF-1 0.02 µg/g/d (n = 9). A control group fed a chow diet was included (n = 6). Liver histology, liver triglycerides content, serum alanine aminotransferase (ALT) activity, adiponectin and leptin serum levels, in vivo muscle strength, tetanic force and muscle fibre cross-sectional area (CSA) were measured. Results: HFD + GH and HFD + IGF-1 groups showed significantly lower ALT activity compared to HFD (p < 0.01). Liver triglyceride content in HFD + GH was decreased compared to HFD (p < 0.01). Histologic steatosis score was increased in HFD and HFD + GH group (p < 0.01), whereas HFD + IGF-1 presented no difference compared to the chow group (p = 0.3). HFD + GH group presented lower serum leptin and adiponectin levels compared to HFD. GH and IGF-1 supplementation therapy reverted HFD-induced reduction in muscle strength and CSA (sarcopenia). Conclusions: GH and IGF-1 supplementation induced significant improvement in liver steatosis, aminotransferases and sarcopenia in a diet-induced NAFLD model. PMID:29724029

  11. Correlation of cell-free DNA plasma concentration with severity of non-alcoholic fatty liver disease.

    PubMed

    Karlas, Thomas; Weise, Lara; Kuhn, Stephanie; Krenzien, Felix; Mehdorn, Matthias; Petroff, David; Linder, Nicolas; Schaudinn, Alexander; Busse, Harald; Keim, Volker; Pratschke, Johann; Wiegand, Johannes; Splith, Katrin; Schmelzle, Moritz

    2017-05-19

    The assessment of fibrosis and inflammatory activity is essential to identify patients with non-alcoholic fatty liver disease (NAFLD) at risk for progressive disease. Serum markers and ultrasound-based methods can replace liver biopsy for fibrosis staging, whereas non-invasive characterization of inflammatory activity remains a clinical challenge. Cell-free DNA (cfDNA) is a novel non-invasive biomarker for assessing cellular inflammation and cell death, which has not been evaluated in NAFLD. Patients and healthy controls from two previous studies were included. NAFLD disease activity and severity were non-invasively characterized by liver stiffness measurement (transient elastography, TE) including steatosis assessment with controlled attenuation parameter (CAP), single-proton magnetic resonance spectroscopy ( 1 H-MRS) for determination of hepatic fat fraction, aminotransferases and serum ferritin. cfDNA levels (90 and 222 bp fragments) were analyzed using quantitative real-time PCR. Fifty-eight NAFLD patients (age 62 ± 11 years, BMI 28.2 ± 3.5 kg/m 2 ) and 13 healthy controls (age 38 ± 12 years, BMI 22.4 ± 2.1 kg/m 2 ) were included. 90 bp cfDNA levels were significantly higher in NAFLD patients compared to healthy controls: 3.7 (1.3-23.1) vs. 2.9 (1.4-4.1) ng/mL (p = 0.014). In the NAFLD cohort, circulating cfDNA correlated significantly with disease activity and severity, especially in patients with elevated liver stiffness (n = 13, 22%) compared to cases with TE values ≤7 kPa: cf90 bp 6.05 (2.41-23.13) vs. 3.16 (1.29-7.31) ng/mL (p < 0.001), and cf222 bp 14.41 (9.27-22.90) vs. 11.32 (6.05-18.28) ng/mL (p = 0.0041). Cell-free DNA plasma concentration correlates with established non-invasive markers of NAFLD activity and severity. Therefore, cfDNA should be further evaluated as biomarker for identifying patients at risk for progressive NAFLD.

  12. Tenosynovitis US scoring systems follow synovitis and clinical scoring systems in RA and are responsive to change after biologic therapy.

    PubMed

    Vlad, Violeta; Berghea, Florian; Micu, Mihaela; Varzaru, Luminita; Bojinca, Mihai; Milicescu, Mihaela; Ionescu, Ruxandra; Naredo, Esperanza

    2015-09-01

    To investigate by ultrasonography (US) in a cohort of active RA patients starting biologic therapy the responsiveness of tenosynovitis of wrist and hands compared to the responsiveness of synovitis in a 6 month period follow-up, to compare the responsiveness of finger flexor tenosynovitis with the responsiveness of wrist extensor tenosynovitis and to describe the subclinical synovitis and tenosynovitis in RA patients in clinical remission. Fifty seven patients with active RA starting biologic therapy were included. Clinical, laboratory, and US evaluations were performed at baseline, 1, and 6 months. US evaluation included wrist and MCPs 2-5 joints, bilaterally for synovitis and extensor tendons compartments 2, 4, and 6 and finger flexors 2-5 for tenosynovitis. Eighteen US scores based on semiquantitative or binary grades were calculated at each visit. Responsiveness of synovitis and tenosynovitis scores was calculated using the standardized response mean (SRM). The responsiveness of US tenosynovitis was lower comparing with the responsiveness of US synovitis but both showed large effect of therapy. Furthermore, tenosynovitis responsiveness was similar to CRP responsiveness (SRM -0.90). Finger flexors tenosynovitis showed a higher responsiveness than extensor tenosynovitis on GS (-0.94 compared to -0.63) and a lower SRM on PD (-0.56 compared to -0.85). Tenosynovitis scores remission was overlapping clinical remission according to CDAI and SDAI in 100% of cases. Overall there was less subclinical tenosynovitis than subclinical synovitis at final visit according to clinical activity indices. Tenosynovitis US scoring in RA may be as good as synovitis scoring for characterization of disease activity and responsiveness.

  13. Differences of wells scores accuracy, caprini scores and padua scores in deep vein thrombosis diagnosis

    NASA Astrophysics Data System (ADS)

    Gatot, D.; Mardia, A. I.

    2018-03-01

    Deep Vein Thrombosis (DVT) is the venous thrombus in lower limbs. Diagnosis is by using venography or ultrasound compression. However, these examinations are not available yet in some health facilities. Therefore many scoring systems are developed for the diagnosis of DVT. The scoring method is practical and safe to use in addition to efficacy, and effectiveness in terms of treatment and costs. The existing scoring systems are wells, caprini and padua score. There have been many studies comparing the accuracy of this score but not in Medan. Therefore, we are interested in comparative research of wells, capriniand padua score in Medan.An observational, analytical, case-control study was conducted to perform diagnostic tests on the wells, caprini and padua score to predict the risk of DVT. The study was at H. Adam Malik Hospital in Medan.From a total of 72 subjects, 39 people (54.2%) are men and the mean age are 53.14 years. Wells score, caprini score and padua score has a sensitivity of 80.6%; 61.1%, 50% respectively; specificity of 80.65; 66.7%; 75% respectively, and accuracy of 87.5%; 64.3%; 65.7% respectively.Wells score has better sensitivity, specificity and accuracy than caprini and padua score in diagnosing DVT.

  14. Modeling complexity in pathologist workload measurement: the Automatable Activity-Based Approach to Complexity Unit Scoring (AABACUS).

    PubMed

    Cheung, Carol C; Torlakovic, Emina E; Chow, Hung; Snover, Dale C; Asa, Sylvia L

    2015-03-01

    Pathologists provide diagnoses relevant to the disease state of the patient and identify specific tissue characteristics relevant to response to therapy and prognosis. As personalized medicine evolves, there is a trend for increased demand of tissue-derived parameters. Pathologists perform increasingly complex analyses on the same 'cases'. Traditional methods of workload assessment and reimbursement, based on number of cases sometimes with a modifier (eg, the relative value unit (RVU) system used in the United States), often grossly underestimate the amount of work needed for complex cases and may overvalue simple, small biopsy cases. We describe a new approach to pathologist workload measurement that aligns with this new practice paradigm. Our multisite institution with geographically diverse partner institutions has developed the Automatable Activity-Based Approach to Complexity Unit Scoring (AABACUS) model that captures pathologists' clinical activities from parameters documented in departmental laboratory information systems (LISs). The model's algorithm includes: 'capture', 'export', 'identify', 'count', 'score', 'attribute', 'filter', and 'assess filtered results'. Captured data include specimen acquisition, handling, analysis, and reporting activities. Activities were counted and complexity units (CUs) generated using a complexity factor for each activity. CUs were compared between institutions, practice groups, and practice types and evaluated over a 5-year period (2008-2012). The annual load of a clinical service pathologist, irrespective of subspecialty, was ∼40,000 CUs using relative benchmarking. The model detected changing practice patterns and was appropriate for monitoring clinical workload for anatomical pathology, neuropathology, and hematopathology in academic and community settings, and encompassing subspecialty and generalist practices. AABACUS is objective, can be integrated with an LIS and automated, is reproducible, backwards compatible

  15. Rapid activity prediction of HIV-1 integrase inhibitors: harnessing docking energetic components for empirical scoring by chemometric and artificial neural network approaches

    NASA Astrophysics Data System (ADS)

    Thangsunan, Patcharapong; Kittiwachana, Sila; Meepowpan, Puttinan; Kungwan, Nawee; Prangkio, Panchika; Hannongbua, Supa; Suree, Nuttee

    2016-06-01

    Improving performance of scoring functions for drug docking simulations is a challenging task in the modern discovery pipeline. Among various ways to enhance the efficiency of scoring function, tuning of energetic component approach is an attractive option that provides better predictions. Herein we present the first development of rapid and simple tuning models for predicting and scoring inhibitory activity of investigated ligands docked into catalytic core domain structures of HIV-1 integrase (IN) enzyme. We developed the models using all energetic terms obtained from flexible ligand-rigid receptor dockings by AutoDock4, followed by a data analysis using either partial least squares (PLS) or self-organizing maps (SOMs). The models were established using 66 and 64 ligands of mercaptobenzenesulfonamides for the PLS-based and the SOMs-based inhibitory activity predictions, respectively. The models were then evaluated for their predictability quality using closely related test compounds, as well as five different unrelated inhibitor test sets. Weighting constants for each energy term were also optimized, thus customizing the scoring function for this specific target protein. Root-mean-square error (RMSE) values between the predicted and the experimental inhibitory activities were determined to be <1 (i.e. within a magnitude of a single log scale of actual IC50 values). Hence, we propose that, as a pre-functional assay screening step, AutoDock4 docking in combination with these subsequent rapid weighted energy tuning methods via PLS and SOMs analyses is a viable approach to predict the potential inhibitory activity and to discriminate among small drug-like molecules to target a specific protein of interest.

  16. Inhibiting poly ADP-ribosylation increases fatty acid oxidation and protects against fatty liver disease.

    PubMed

    Gariani, Karim; Ryu, Dongryeol; Menzies, Keir J; Yi, Hyon-Seung; Stein, Sokrates; Zhang, Hongbo; Perino, Alessia; Lemos, Vera; Katsyuba, Elena; Jha, Pooja; Vijgen, Sandrine; Rubbia-Brandt, Laura; Kim, Yong Kyung; Kim, Jung Tae; Kim, Koon Soon; Shong, Minho; Schoonjans, Kristina; Auwerx, Johan

    2017-01-01

    To date, no pharmacological therapy has been approved for non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the therapeutic potential of poly ADP-ribose polymerase (PARP) inhibitors in mouse models of NAFLD. As poly ADP-ribosylation (PARylation) of proteins by PARPs consumes nicotinamide adenine dinucleotide (NAD + ), we hypothesized that overactivation of PARPs drives NAD + depletion in NAFLD. Therefore, we assessed the effectiveness of PARP inhibition to replenish NAD + and activate NAD + -dependent sirtuins, hence improving hepatic fatty acid oxidation. To do this, we examined the preventive and therapeutic benefits of the PARP inhibitor (PARPi), olaparib, in different models of NAFLD. The induction of NAFLD in C57BL/6J mice using a high-fat high-sucrose (HFHS)-diet increased PARylation of proteins by PARPs. As such, increased PARylation was associated with reduced NAD + levels and mitochondrial function and content, which was concurrent with elevated hepatic lipid content. HFHS diet supplemented with PARPi reversed NAFLD through repletion of NAD + , increasing mitochondrial biogenesis and β-oxidation in liver. Furthermore, PARPi reduced reactive oxygen species, endoplasmic reticulum stress and fibrosis. The benefits of PARPi treatment were confirmed in mice fed with a methionine- and choline-deficient diet and in mice with lipopolysaccharide-induced hepatitis; PARP activation was attenuated and the development of hepatic injury was delayed in both models. Using Sirt1 hep-/- mice, the beneficial effects of a PARPi-supplemented HFHS diet were found to be Sirt1-dependent. Our study provides a novel and practical pharmacological approach for treating NAFLD, fueling optimism for potential clinical studies. Non-alcoholic fatty liver disease (NAFLD) is now considered to be the most common liver disease in the Western world and has no approved pharmacological therapy. PARP inhibitors given as a treatment in two different mouse

  17. The Potential Biomarkers to Identify the Development of Steatosis in Hyperuricemia

    PubMed Central

    He, Xiaojuan; Lu, Cheng; He, Bing; Niu, Xuyan; Xiao, Cheng; Xu, Gang; Bian, Zhaoxiang; Zu, Xianpeng; Zhang, Ge; Zhang, Weidong; Lu, Aiping

    2016-01-01

    Hyperuricemia (HU) often progresses to combine with non-alcoholic fatty liver disease (NAFLD) in the clinical scenario, which further exacerbates metabolic disorders; early detection of biomarkers, if obtained during the HU progression, may be beneficial for preventing its combination with NAFLD. This study aimed to decipher the biomarkers and mechanisms of the development of steatosis in HU. Four groups of subjects undergoing health screening, including healthy subjects, subjects with HU, subjects with HU combined with NAFLD (HU+NAFLD) and subjects with HU initially and then with HU+NAFLD one year later (HU→HU+NAFLD), were recruited in this study. The metabolic profiles of all subjects’ serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolomic data from subjects with HU and HU+NAFLD were compared, and the biomarkers for the progression from HU to HU+NAFLD were predicted. The metabolomic data from HU→HU+NAFLD subjects were collected for further verification. The results showed that the progression was associated with disturbances of phospholipase metabolism, purine nucleotide degradation and Liver X receptor/retinoic X receptor activation as characterized by up-regulated phosphatidic acid, cholesterol ester (18:0) and down-regulated inosine. These metabolic alterations may be at least partially responsible for the development of steatosis in HU. This study provides a new paradigm for better understanding and further prevention of disease progression. PMID:26890003

  18. Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease.

    PubMed

    Alazawi, William; Bernabe, Eduardo; Tai, David; Janicki, Tomasz; Kemos, Polychronis; Samsuddin, Salma; Syn, Wing-Kin; Gillam, David; Turner, Wendy

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) has a bidirectional association with metabolic syndrome. It affects up to 30% of the general population, 70% of individuals with diabetes and 90% with obesity. The main histological hallmark of progressive NAFLD is fibrosis. There is a bidirectional epidemiological link between periodontitis and metabolic syndrome. NAFLD, periodontitis and diabetes share common risk factors, are characterised by inflammation and associated with changes in commensal bacteria. Therefore we tested the hypothesis that periodontitis is associated with NAFLD and with significant fibrosis in two study groups. We analyzed data from a population-based survey and a patient-based study. NHANES III participants with abdominal ultrasound and sociodemographic, clinical, and oral examination data were extracted and appropriate weighting applied. In a separate patient-based study, consenting patients with biopsy-proved NAFLD (or with liver indices too mild to justify biopsy) underwent dental examination. Basic Periodontal Examination score was recorded. In NHANES, periodontitis was significantly associated with steatosis in 8172 adults even after adjusting for sociodemographic factors. However, associations were fully explained after accounting for features of metabolic syndrome. In the patient-based study, periodontitis was significantly more common in patients with biopsy-proven NASH and any fibrosis (F0-F4) than without NASH (p = 0.009). Periodontitis was more common in patients with NASH and significant fibrosis (F2-4) than mild or no fibrosis (F0-1, p = 0.04). Complementary evidence from an epidemiological survey and a clinical study show that NAFLD is associated with periodontitis and that the association is stronger with significant liver fibrosis.

  19. Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet123

    PubMed Central

    Chen, Yung-Ju; Wallig, Matthew A; Jeffery, Elizabeth H

    2016-01-01

    Background: The high-fat and high-sugar Westernized diet that is popular worldwide is associated with increased body fat accumulation, which has been related to the development of nonalcoholic fatty liver disease (NAFLD). Without treatment, NAFLD may progress to hepatocellular carcinoma (HCC), a cancer with a high mortality rate. The consumption of broccoli in the United States has greatly increased in the last 2 decades. Epidemiologic studies show that incorporating brassica vegetables into the daily diet lowers the risk of several cancers, although, to our knowledge, this is the first study to evaluate HCC prevention through dietary broccoli. Objective: We aimed to determine the impact of dietary broccoli on hepatic lipid metabolism and the progression of NAFLD to HCC. Our hypothesis was that broccoli decreases both hepatic lipidosis and the development of HCC in a mouse model of Western diet–enhanced liver cancer. Methods: Adult 5-wk-old male B6C3F1 mice received a control diet (AIN-93M) or a Western diet (high in lard and sucrose, 19% and 31%, wt:wt, respectively), with or without freeze-dried broccoli (10%, wt:wt). Starting the following week, mice were treated once per week with diethylnitrosamine (DEN; 45 mg/kg body weight intraperitoneally at ages 6, 7, 8, 10, 11, and 12 wk). Hepatic gene expression, lipidosis, and tumor outcomes were analyzed 6 mo later, when mice were 9 mo old. Results: Mice receiving broccoli exhibited lower hepatic triglycerides (P < 0.001) and NAFLD scores (P < 0.0001), decreased plasma alanine aminotransferase (P < 0.0001), suppressed activation of hepatic CD68+ macrophages (P < 0.0001), and slowed initiation and progression of hepatic neoplasm. Hepatic Cd36 was downregulated by broccoli feeding (P = 0.006), whereas microsomal triglyceride transfer protein was upregulated (P = 0.045), supporting the finding that dietary broccoli decreased hepatic triglycerides. Conclusion: Long-term consumption of whole broccoli countered both NAFLD

  20. Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet.

    PubMed

    Chen, Yung-Ju; Wallig, Matthew A; Jeffery, Elizabeth H

    2016-03-01

    The high-fat and high-sugar Westernized diet that is popular worldwide is associated with increased body fat accumulation, which has been related to the development of nonalcoholic fatty liver disease (NAFLD). Without treatment, NAFLD may progress to hepatocellular carcinoma (HCC), a cancer with a high mortality rate. The consumption of broccoli in the United States has greatly increased in the last 2 decades. Epidemiologic studies show that incorporating brassica vegetables into the daily diet lowers the risk of several cancers, although, to our knowledge, this is the first study to evaluate HCC prevention through dietary broccoli. We aimed to determine the impact of dietary broccoli on hepatic lipid metabolism and the progression of NAFLD to HCC. Our hypothesis was that broccoli decreases both hepatic lipidosis and the development of HCC in a mouse model of Western diet-enhanced liver cancer. Adult 5-wk-old male B6C3F1 mice received a control diet (AIN-93M) or a Western diet (high in lard and sucrose, 19% and 31%, wt:wt, respectively), with or without freeze-dried broccoli (10%, wt:wt). Starting the following week, mice were treated once per week with diethylnitrosamine (DEN; 45 mg/kg body weight intraperitoneally at ages 6, 7, 8, 10, 11, and 12 wk). Hepatic gene expression, lipidosis, and tumor outcomes were analyzed 6 mo later, when mice were 9 mo old. Mice receiving broccoli exhibited lower hepatic triglycerides (P < 0.001) and NAFLD scores (P < 0.0001), decreased plasma alanine aminotransferase (P < 0.0001), suppressed activation of hepatic CD68(+) macrophages (P < 0.0001), and slowed initiation and progression of hepatic neoplasm. Hepatic Cd36 was downregulated by broccoli feeding (P = 0.006), whereas microsomal triglyceride transfer protein was upregulated (P = 0.045), supporting the finding that dietary broccoli decreased hepatic triglycerides. Long-term consumption of whole broccoli countered both NAFLD development enhanced by a Western diet and hepatic

  1. MicroRNA changes, activation of progenitor cells and severity of liver injury in mice induced by choline and folate deficiency.

    PubMed

    Tryndyak, Volodymyr P; Marrone, April K; Latendresse, John R; Muskhelishvili, Levan; Beland, Frederick A; Pogribny, Igor P

    2016-02-01

    Dietary deficiency in methyl-group donors and cofactors induces liver injury that resembles many pathophysiological and histopathological features of human nonalcoholic fatty liver disease (NAFLD), including an altered expression of microRNAs (miRNAs). We evaluated the consequences of a choline- and folate-deficient (CFD) diet on the expression of miRNAs in the livers of male A/J and WSB/EiJ mice. The results demonstrate that NAFLD-like liver injury induced by the CFD diet in A/J and WSB/EiJ mice was associated with marked alterations in hepatic miRNAome profiles, with the magnitude of miRNA expression changes being greater in WSB/EiJ mice, the strain characterized by the greatest severity of liver injury. Specifically, WSB/EiJ mice exhibited more prominent changes in the expression of common miRNAs as compared to A/J mice and distinct miRNA alterations, including the overexpression of miR-134, miR-409-3p, miR-410 and miR-495 miRNAs that were accompanied by an activation of hepatic progenitor cells and fibrogenesis. This in vivo finding was further confirmed by in vitro experiments showing an overexpression of these miRNAs in undifferentiated progenitor hepatic HepaRG cells compared to in fully differentiated HepaRG cells. Additionally, a marked elevation of miR-134, miR-409-3p, miR-410 and miR-495 was found in plasma of WSB/EiJ mice fed the CFD diet, while none of the miRNAs was changed in plasma of A/J mice. These findings suggest that miRNAs may be crucial regulators responsible for the progression of NAFLD and may be useful as noninvasive diagnostic indicators of the severity and progression of NAFLD. Published by Elsevier Inc.

  2. [CYP7A1 gene polymorphism and the characteristics of dyslipidemias in patients with nonalcoholic fatty liver disease concurrent with hypothyroidism].

    PubMed

    Zhaldak, D A; Melekhovets, O K; Orlovskyi, V F

    To investigate the association of the polymorphic variants -204A > C (rs 3808607) in the CYP7A1 gene with the development of dyslipidemias in healthy individuals, in patients with non-alcoholic fatty liver disease (NAFLD) and in those with NAFLD concurrent with hypothyroidism. DNA samples and lipidograms were examined in 180 patients, including 60 healthy individuals (Group 1), 60 patients with hypothyroidism concurrent with NAFLD (Group 2), and 60 patients with NAFLD (Group 3). All the patients underwent ultrasound examination of the thyroid gland and abdominal cavity organs; FibroMax scores were calculated. All the study groups most frequently showed a homozygous AA genotype (86.6% of cases in Group 1, 80% in Group 2, and 83.3% in Group 3). The development of NAFLD in CC genotype carriers is characterized by the most pronounced changes in lipid metabolism (atherogenic index (AI), 7.32 in Group 3) compared to the genotypes AA (AI, 4.56 in Group 2 and 1.73 in Group 1) and CC (AI, 6.43 in Group 2 and 2.52 in Group 1) in functional insufficiency of thyroid hormones and relative normal conditions. The analysis of the relationship of polymorphic variants CYP7A1 rs 38088607 to lipid metabolic disturbances in the study groups showed that the significantly higher levels of atherogenic cholesterol fractions were determined in the CC genotype compared to AA genotype carriers and they did not depend on the presence of NAFLD and hypothyroidism. The findings make it possible to consider the AA homozygous genotype of variant mutation CYP7A1 rs 38088607 as protective against dyslipidemia. However, in functional insufficiency of thyroid hormones, the level of triglycerides is significantly higher in both genotypes, which suggests that hypothyroidism plays an essential role in the development of dyslipidemia and NAFLD.

  3. Total sesquiterpene glycosides from Loquat (Eriobotrya japonica) leaf alleviate high-fat diet induced non-alcoholic fatty liver disease through cytochrome P450 2E1 inhibition.

    PubMed

    Jian, Tunyu; Ao, Xiancan; Wu, YueXian; Lv, Han; Ma, Li; Zhao, Lei; Tong, Bei; Ren, Bingru; Chen, Jian; Li, Weilin

    2017-07-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, which affects 20-40% of the population in the world. Loquat (Eriobotrya japonica) Leaf possesses several pharmacological actions. Many sesquiterpene glycosides were reported to be isolated exclusively from the Loquat Leaf, however, their biological activity has been rarely investigated. The present study was designed to evaluate the pharmacological effect of total sesquiterpene glycosides (TSG) in high-fat diet (HFD) induced NAFLD mice with its related mechanisms of action. Mice were fed with a normal diet or HFD for 8 weeks. TSG (25 and 100mg/kg/day), simvastatin (10mg/kg/day) or vehicle were orally administered for last 4 weeks of the 8-week HFD feeding period. From the result, it was showed that TSG significantly reduced the body weight and fat deposition in the liver of NAFLD mice. It also decreased total cholesterol (TC) and triglyceride (TG) contents in the serum. Compared with NAFLD mice, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were increased and decreased after the administration of TSG in a dose of 100mg/kg, respectively. TSG reduced alanine aminotransferase (ALT) activity as well. Finally, TSG was found to suppress the expression of cytochrome P450 2E1 (CYP2E1) and the phosphorylation of c-jun terminal kinase (JNK) in NAFLD mice. In summary, this study demonstrates that TSG reduces oxidative stress by downregulating of CYP2E1 expression and JNK phosphorylation in NAFLD, and alleviates NAFLD ultimately. TSG potentially serves as bioactive compounds for the treatment of NAFLD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Mangiferin ameliorates fatty liver via modulation of autophagy and inflammation in high-fat-diet induced mice.

    PubMed

    Wang, Hu; Zhu, Yang-Yang; Wang, Li; Teng, Tian; Zhou, Meng; Wang, Shu-Guang; Tian, Yi-Zhu; Du, Lei; Yin, Xiao-Xing; Sun, Ying

    2017-12-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. The progression of NAFLD is complex and associated with inflammation, oxidative stress, autophagy, endoplasmic reticulum stress, and insulin resistance. Mangiferin, a natural C-glucosyl xanthone, has been reported to show multiple biological activities. The aim of this study was to investigate the therapeutic effect of mangiferin on NAFLD and the underlying molecular mechanism. We established a mouse model of NAFLD using a high-fat diet (HFD), and injected the mice with different doses of mangiferin (15, 30, and 60mg/kg, intraperitoneal) for 12 weeks. Liver tissue was assessed to evaluate changes in inflammatory responses, autophagy, and glycolipid metabolism. We found that mangiferin decreased body weight, as well as the levels of triglycerides and total cholesterol in plasma and the liver. It also increased glucose tolerance in HFD-fed mice. In addition, mangiferin decreased inflammatory responses by inhibiting the activities of nuclear factor kappa B and c-Jun N-terminal kinase, regulated autophagy via the AMP-activated protein kinase/mechanistic target of rapamycin signaling pathway, and improved glycolipid metabolism via modulation of the insulin receptor substrate/phosphoinositide 3-kinase/protein kinase B signaling pathway. This study demonstrated that mangiferin significantly ameliorates NAFLD development in HFD-fed mice by inhibiting inflammatory responses, activating autophagy, and improving glycolipid metabolism. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Sirtuin 3 (SIRT3) Regulates α-Smooth Muscle Actin (α-SMA) Production through the Succinate Dehydrogenase-G Protein-coupled Receptor 91 (GPR91) Pathway in Hepatic Stellate Cells.

    PubMed

    Li, Ying Hui; Choi, Dae Hee; Lee, Eun Hye; Seo, Su Ryeon; Lee, Seungkoo; Cho, Eun-Hee

    2016-05-06

    Sirtuin 3 (SIRT3) is an NAD(+)-dependent protein deacetylase. Recent studies have shown that SIRT3 expression is decreased in nonalcoholic fatty liver disease (NAFLD). Moreover, SIRT3 is a key regulator of succinate dehydrogenase (SDH), which catalyzes the oxidation of succinate to fumarate. Increased succinate concentrations and the specific G protein-coupled receptor 91 (GPR91) are involved in the activation of hepatic stellate cells (HSCs). In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD. Our goal was also to determine whether succinate released from hepatocytes regulated HSC activation. Inhibiting SIRT3 using SIRT3 siRNA exacerbated HSC activation via the SDH-succinate-GPR91 pathway, and SIRT3 overexpression or honokiol treatment attenuated HSC activation in vitro In isolated liver and HSCs from methionine- and choline-deficient (MCD) diet-induced NAFLD, the expression of SIRT3 and SDH activity was decreased, and the succinate concentrations and GPR91 expression were increased. Moreover, we found that GPR91 knockdown or resveratrol treatment improved the steatosis in MCD diet-fed mice. This investigation revealed a novel mechanism of the SIRT3-SDH-GPR91 cascade in MCD diet-induced HSC activation in NAFLD. These findings highlight the biological significance of novel strategies aimed at targeting SIRT3 and GPR91 in HSCs with the goal of improving NAFLD treatment. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Adherence to Mediterranean Diet and Non-Alcoholic Fatty Liver Disease: Effect on Insulin Resistance.

    PubMed

    Baratta, Francesco; Pastori, Daniele; Polimeni, Licia; Bucci, Tommaso; Ceci, Fabrizio; Calabrese, Cinzia; Ernesti, Ilaria; Pannitteri, Gaetano; Violi, Francesco; Angelico, Francesco; Del Ben, Maria

    2017-12-01

    The prevalence of cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD), is increasing in western countries, because of changes in lifestyle and dietary habits. Mediterranean Diet (Med-Diet) is effective for cardiovascular prevention, but its relationship with NAFLD has been scarcely investigated. We included 584 consecutive outpatients presenting with one or more cardiovascular risk factor such as type 2 diabetes mellitus (T2DM), arterial hypertension, overweight/obesity, and dyslipidemia. Liver steatosis was assessed using ultrasonography. Med-Diet adherence was investigated by a validated semiquantitative nine-item dietary questionnaire; patients were divided into low, intermediate, and high adherence. Insulin resistance was defined by the 75th percentile of homeostasis model of insulin resistance (HOMA-IR; ≥3.8). The mean age was 56.2±12.4 years and 38.2% were women. Liver steatosis was present in 82.7%, and its prevalence decreased from low to high adherence group (96.5% vs. 71.4%, P<0.001). In a multiple logistic regression analysis, hypertriglyceridemia (odds ratio (OR): 2.913; P=0.002), log (ALT) (OR: 6.186; P<0.001), Med-Diet adherence (intermediate vs. low OR: 0.115; P=0.041, high vs. low OR: 0.093; P=0.030), T2DM (OR: 3.940; P=0.003), and high waist circumference (OR: 3.012; P<0.001) were associated with NAFLD. Among single foods, low meat intake (OR: 0.178; P<0.001) was inversely significantly associated with NAFLD. In 334 non-diabetic NAFLD patients, age (OR: 1.035, P=0.025), high waist circumference (OR: 7.855, P<0.001), hypertriglyceridemia (OR: 2.152, P=0.011), and Log (ALT) (OR: 2.549, P=0.002) were directly associated with HOMA-IR, whereas Med-Diet score was inversely associated (OR: 0.801, P=0.018). We found an inverse relationship between Med-Diet and NAFLD prevalence. Among NAFLD patients, good adherence to Med-Diet was associated with lower insulin resistance. Our findings suggest that Med-Diet may be a beneficial

  7. Reference Values for the Marx Activity Rating Scale in a Young Athletic Population: History of Knee Ligament Injury Is Associated With Higher Scores.

    PubMed

    Cameron, Kenneth L; Peck, Karen Y; Thompson, Brandon S; Svoboda, Steven J; Owens, Brett D; Marshall, Stephen W

    2015-01-01

    Activity-related patient-reported outcome measures are an important component of assessment after knee ligament injury in young and physically active patients; however, normative data for most activity scales are limited. To present reference values by sex for the Marx Activity Rating Scale (MARS) within a young and physically active population while accounting for knee ligament injury history and sex. Cross-sectional study. Level 2. All incoming freshman entering a US Service Academy in June of 2011 were recruited to participate in this study. MARS was administered to 1169 incoming freshmen (203 women) who consented to participate within the first week of matriculation. All subjects were deemed healthy and medically fit for military service on admission. Subjects also completed a baseline questionnaire that asked for basic demographic information and injury history. We calculated means with standard deviations, medians with interquartile ranges, and percentiles for ordinal and continuous variables, and frequencies and proportions for dichotomous variables. We also compared median scores by sex and history of knee ligament injury using the Kruskal-Wallis test. MARS was the primary outcome of interest. The median MARS score was significantly higher for men when compared with women (χ(2) = 13.22, df = 1, P < 0.001) with no prior history of knee ligament injury. In contrast, there was no significant difference in median MARS scores between men and women (χ(2) = 0.47, df = 1, P = 0.493) who reported a history of injury. Overall, median MARS scores were significantly higher among those who reported a history of knee ligament injury when compared with those who did not (χ(2) = 9.06, df = 1, P = 0.003). Assessing activity as a patient-reported outcome after knee ligament injury is important, and reference values for these instruments need to account for the influence of prior injury and sex. © 2015 The Author(s).

  8. Improvements in fundamental movement skill competency mediate the effect of the SCORES intervention on physical activity and cardiorespiratory fitness in children.

    PubMed

    Cohen, Kristen E; Morgan, Philip J; Plotnikoff, Ronald C; Barnett, Lisa M; Lubans, David R

    2015-01-01

    Numerous studies have identified a positive association between fundamental movement skill (FMS) competency and physical activity in children; however, the causal pathways have not been established. The aim of this study is to determine if changes in FMS competency mediated the effect of the Supporting Children's Outcomes using Rewards, Exercise and Skills (SCORES) intervention on physical activity and cardiorespiratory fitness in children. Eight primary schools (25 classes) and 460 children (aged 8.5 ± 0.6, 54% girls) were randomised to the SCORES intervention or control group for the 12-month study. The outcomes were accelerometer-determined moderate-to-vigorous physical activity (MVPA) and cardiorespiratory fitness. The hypothesised mediators were actual FMS competency and perceived sport competence. Mediation analyses were conducted using multilevel linear analysis in MPlus. From the original sample, 138 (30.0%) and 370 (80.4%) children provided useable physical activity and cardiorespiratory fitness data at post-test assessments. There were significant treatment effects for locomotor skills and overall FMSs. Changes in MVPA were associated with changes in object-control skills, overall FMSs and perceived competence. The overall FMSs had a significant mediating effect on MVPA (AB = 2.09, CI = 0.01-4.55). Overall FMSs (AB = 1.19, CI = 0.002-2.79) and locomotor skills (AB = 0.74, CI = 0.01-1.69) had a significant mediating effect on cardiorespiratory fitness. The results of this study conclude that actual but not perceived movement skill competency mediated the effect of the SCORES intervention on physical activity and cardiorespiratory fitness.

  9. Patients with lower activation associated with higher costs; delivery systems should know their patients' 'scores'.

    PubMed

    Hibbard, Judith H; Greene, Jessica; Overton, Valerie

    2013-02-01

    Patient activation is a term that describes the skills and confidence that equip patients to become actively engaged in their health care. Health care delivery systems are turning to patient activation as yet another tool to help them and their patients improve outcomes and influence costs. In this article we examine the relationship between patient activation levels and billed care costs. In an analysis of 33,163 patients of Fairview Health Services, a large health care delivery system in Minnesota, we found that patients with the lowest activation levels had predicted average costs that were 8 percent higher in the base year and 21 percent higher in the first half of the next year than the costs of patients with the highest activation levels, both significant differences. What's more, patient activation was a significant predictor of cost even after adjustment for a commonly used "risk score" specifically designed to predict future costs. As health care delivery systems move toward assuming greater accountability for costs and outcomes for defined patient populations, knowing patients' ability and willingness to manage their health will be a relevant piece of information integral to health care providers' ability to improve outcomes and lower costs.

  10. "Always Look on the Bright Side of Life!" - Higher Hypomania Scores Are Associated with Higher Mental Toughness, Increased Physical Activity, and Lower Symptoms of Depression and Lower Sleep Complaints.

    PubMed

    Jahangard, Leila; Rahmani, Anahita; Haghighi, Mohammad; Ahmadpanah, Mohammad; Sadeghi Bahmani, Dena; Soltanian, Ali R; Shirzadi, Shahriar; Bajoghli, Hafez; Gerber, Markus; Holsboer-Trachsler, Edith; Brand, Serge

    2017-01-01

    Background: In the present study, we explored the associations between hypomania, symptoms of depression, sleep complaints, physical activity and mental toughness. The latter construct has gained interest for its association with a broad variety of favorable behavior in both clinical and non-clinical samples. Subjects and Methods: The non-clinical sample consisted of 206 young adults ( M = 21.3 years; age range: 18-24 years; 57.3% males). They completed questionnaires covering hypomania, mental toughness, symptoms of depression, physical activity, and sleep quality. Results: Higher hypomania scores were associated with higher mental toughness, increased physical activity, lower symptoms of depression and lower sleep complaints. No gender differences were observed. Higher hypomania scores were predicted by higher scores of mental toughness subscales of control and challenge, and physical activity. Conclusion: The pattern of results suggests that among a non-clinical sample of young adults, self-rated hypomania scores were associated with higher scores on mental toughness and physical activity, along with lower depression and sleep complaints. The pattern of results further suggests that hypomania traits are associated with a broad range of favorable psychological, behavioral and sleep-related traits, at least among a non-clinical sample of young adults.

  11. Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease.

    PubMed

    Guo, Rui; Liong, Emily C; So, Kwok Fai; Fung, Man-Lung; Tipoe, George L

    2015-04-01

    Non-alcoholic fatty liver disease (NAFLD) refers to any fatty liver disease that is not due to excessive use of alcohol. NAFLD probably results from abnormal hepatic lipid metabolism and insulin resistance. Aerobic exercise is shown to improve NAFLD. This review aimed to evaluate the molecular mechanisms involved in the beneficial effects of aerobic exercise on NAFLD. We searched articles in English on the role of aerobic exercise in NAFLD therapy in PubMed. The mechanisms of chronic aerobic exercise in regulating the outcome of NAFLD include: (i) reducing intrahepatic fat content by down-regulating sterol regulatory element-binding protein-1c and up-regulating peroxisome proliferator-activated receptor gamma expression levels; (ii) decreasing hepatic oxidative stress through modulating the reactive oxygen species, and enhancing antioxidant enzymes such as catalase and glutathione peroxidase; (iii) ameliorating hepatic inflammation via the inhibition of pro-inflammatory mediators such as tumor necrosis factor-alpha and interleukin-1 beta; (iv) attenuating mitochondrial dependent apoptosis by reducing cytochrome C released from the mitochondria to the cytosol; and (v) inducing hepato-protective autophagy. Aerobic exercise, via different mechanisms, significantly decreases the fat content of the liver and improves the outcomes of patients with NAFLD.

  12. Explicit treatment of active-site waters enhances quantum mechanical/implicit solvent scoring: Inhibition of CDK2 by new pyrazolo[1,5-a]pyrimidines.

    PubMed

    Hylsová, Michaela; Carbain, Benoit; Fanfrlík, Jindřich; Musilová, Lenka; Haldar, Susanta; Köprülüoğlu, Cemal; Ajani, Haresh; Brahmkshatriya, Pathik S; Jorda, Radek; Kryštof, Vladimír; Hobza, Pavel; Echalier, Aude; Paruch, Kamil; Lepšík, Martin

    2017-01-27

    We present comprehensive testing of solvent representation in quantum mechanics (QM)-based scoring of protein-ligand affinities. To this aim, we prepared 21 new inhibitors of cyclin-dependent kinase 2 (CDK2) with the pyrazolo[1,5-a]pyrimidine core, whose activities spanned three orders of magnitude. The crystal structure of a potent inhibitor bound to the active CDK2/cyclin A complex revealed that the biphenyl substituent at position 5 of the pyrazolo[1,5-a]pyrimidine scaffold was located in a previously unexplored pocket and that six water molecules resided in the active site. Using molecular dynamics, protein-ligand interactions and active-site water H-bond networks as well as thermodynamics were probed. Thereafter, all the inhibitors were scored by the QM approach utilizing the COSMO implicit solvent model. Such a standard treatment failed to produce a correlation with the experiment (R 2  = 0.49). However, the addition of the active-site waters resulted in significant improvement (R 2  = 0.68). The activities of the compounds could thus be interpreted by taking into account their specific noncovalent interactions with CDK2 and the active-site waters. In summary, using a combination of several experimental and theoretical approaches we demonstrate that the inclusion of explicit solvent effects enhance QM/COSMO scoring to produce a reliable structure-activity relationship with physical insights. More generally, this approach is envisioned to contribute to increased accuracy of the computational design of novel inhibitors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Effect of silymarin plus vitamin E in patients with non-alcoholic fatty liver disease. A randomized clinical pilot study.

    PubMed

    Aller, R; Izaola, O; Gómez, S; Tafur, C; González, G; Berroa, E; Mora, N; González, J M; de Luis, D A

    2015-08-01

    Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized health problem. Various treatment strategies such as thiazolidinediones, metformin, lipid-lowering agents and antioxidants have been evaluated. So far, no single intervention has convincingly improved liver histology. Experience of using silymarin alone or in combination with other agents in patients with NAFLD is limited in the medical literature. The present study was conducted to evaluate the efficacy of silymarin plus vitamin E in the treatment of NAFLD. A sample of 36 patients was enrolled. The diagnosis of NAFLD was confirmed by percutaneous liver biopsy. All patients were randomized to one of the following intervention groups: group I: treated with 2 tablets per day of silymarin plus vitamin E (Eurosil 85®, MEDAS SL) and a lifestyle modification program consisting of hypocaloric diet (1520 kcal, 52% of carbohydrates, 25% of lipids and 23% of proteins) and exercise for 3 months and group II (only with the hypocaloric diet). Anthropometric variables as waist circumference, weight, body mass index (BMI) were measured. Biochemical parameters: Glucose, triglycerides, AST, ALT, GGt levels and insulin resistance (HOMA-IR) were determined under fasting conditions. Non-invasive NAFLD-index were applied before and after the treatments: Fatty liver index (FLI), liver accumulation product (LAP) and NAFLD-Fibrosis score (FS). The mean age was 47.4 ± 11.2 years old (range 18-67); 22 men and 14 women. In group I, 11 patients (61%) have a NAS-score > 5 and 10 (55.5%) in the group II (NS). Anthropometric parameters decreased after treatment in both groups. Patients in both groups showed a decrease in GGt levels after treatment (group I: 68 IU/L vs. 46.2 ± 27 IU/L; p < 0.05 and group II 80.5 ± 46 IU/L vs. 50.3 ± 27 IU/L; p < 0.05). Only in group II we observed a significant decrease in AST and ALT levels. In both groups, we observed a decrease in: FLI index (group I: 86.2 ± 19 vs. 76.9 + 20; p < 0

  14. Role of exercise in optimizing the functional status of patients with nonalcoholic fatty liver disease.

    PubMed

    Gerber, Lynn H; Weinstein, Ali; Pawloski, Lisa

    2014-02-01

    Nonalcoholic fatty liver disease (NAFLD) is frequently concomitant with obesity. This article discusses factors that influence health and functional outcomes of people who develop NAFLD, including increased burden of illness, whole body function, performance, and perception of self-efficacy. Changes in macronutrients, amount of calories consumed, and decreased physical activity all negatively influence patient outcome. The benefits of exercise in this population are also discussed. To be effective, exercise must be performed, regularly and in conjunction with dietary and other behavioral change. Therefore, a lifelong commitment to exercise, activity, and diet are needed if NAFLD is to be successfully treated. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: Application to acetaminophen

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Michaut, Anaïs; Le Guillou, Dounia; Moreau, Caroline

    Obesity and nonalcoholic fatty liver disease (NAFLD) can increase susceptibility to hepatotoxicity induced by some xenobiotics including drugs, but the involved mechanisms are poorly understood. For acetaminophen (APAP), a role of hepatic cytochrome P450 2E1 (CYP2E1) is suspected since the activity of this enzyme is consistently enhanced during NAFLD. The first aim of our study was to set up a cellular model of NAFLD characterized not only by triglyceride accumulation but also by higher CYP2E1 activity. To this end, human HepaRG cells were incubated for one week with stearic acid or oleic acid, in the presence of different concentrations ofmore » insulin. Although cellular triglycerides and the expression of lipid-responsive genes were similar with both fatty acids, CYP2E1 activity was significantly increased only by stearic acid. CYP2E1 activity was reduced by insulin and this effect was reproduced in cultured primary human hepatocytes. Next, APAP cytotoxicity was assessed in HepaRG cells with or without lipid accretion and CYP2E1 induction. Experiments with a large range of APAP concentrations showed that the loss of ATP and glutathione was almost always greater in the presence of stearic acid. In cells pretreated with the CYP2E1 inhibitor chlormethiazole, recovery of ATP was significantly higher in the presence of stearate with low (2.5 mM) or high (20 mM) concentrations of APAP. Levels of APAP-glucuronide were significantly enhanced by insulin. Hence, HepaRG cells can be used as a valuable model of NAFLD to unveil important metabolic and hormonal factors which can increase susceptibility to drug-induced hepatotoxicity. - Highlights: • Nonalcoholic fatty liver disease (NAFLD) is frequent in obese individuals. • NAFLD can favor hepatotoxicity induced by some drugs including acetaminophen (APAP). • A model of NAFLD was set up by using HepaRG cells incubated with stearate or oleate. • Stearate-loaded HepaRG cells presented higher cytochrome P450 2E1 (CYP2

  16. The Presence of White Matter Lesions Is Associated With the Fibrosis Severity of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Petta, Salvatore; Tuttolomondo, Antonino; Gagliardo, Cesare; Zafonte, Rita; Brancatelli, Giuseppe; Cabibi, Daniela; Cammà, Calogero; Di Marco, Vito; Galvano, Luigi; La Tona, Giuseppe; Licata, Anna; Magliozzo, Franco; Maida, Carlo; Marchesini, Giulio; Merlino, Giovanni; Midiri, Massimo; Parrinello, Gaspare; Torres, Daniele; Pinto, Antonio; Craxì, Antonio

    2016-01-01

    Abstract We tested whether nonalcoholic fatty liver disease (NAFLD) and/or its histological severity are associated with vascular white matter lesions (WML) in patients with biopsy-proven NAFLD and in non-NAFLD controls. Data were recorded in 79 consecutive biopsy-proven NAFLD, and in 82 controls with normal ALT and no history of chronic liver diseases, without ultrasonographic evidence of steatosis and liver stiffness value <6 KPa. All subjects underwent magnetic resonance assessment and WML were classified according to the Fazekas score as absent (0/III), or present (mild I/III; moderate II/III, and severe I/III). For the purpose of analyses, all controls were considered without NASH and without F2–F4 liver fibrosis. WML were found in 26.7% of the entire cohort (43/161), of moderate–severe grade in only 6 cases. The prevalence was similar in NAFLD versus no-NAFLD (29.1% vs 24.3%; P = 0.49), but higher in NASH vs no-NASH (37.7% vs 21.2%, P = 0.02) and F2–F4 vs F0-F1 fibrosis (47.3% vs 20.3%, P = 0.001). In both the entire cohort and in NAFLD, only female gender (OR 4.37, 95% CI: 1.79–10.6, P = 0.001; and OR 5.21, 95% CI: 1.39–19.6, P = 0.01), age > 45 years (OR 3.09, 95% CI: 1.06–9.06, P = 0.03; and OR 11.1, 95% CI: 1.14–108.7, P = 0.03), and F2–F4 fibrosis (OR 3.36, 95% CI: 1.29–8.73, P = 0.01; and OR 5.34, 95% CI: 1.40–20.3, P = 0.01) were independently associated with WML (mostly of mild grade) by multivariate analysis. Among NAFLD, the prevalence of WML progressively increased from patients without (1/18; 5.5%), or with 1 (1/17, 5.8%), to those with 2 (9/30; 30%) and further to those with 3 (12/14; 85.7%) risk factors. The presence of WML is not associated with NAFLD, but with metabolic diseases in general, and fibrosis severity of NAFLD. Clinical implications of this issue need to be assessed by longitudinal studies. PMID:27100443

  17. Measuring self-regulation in a physically active context: Psychometric analyses of scores derived from an observer-rated measure of self-regulation.

    PubMed

    Lakes, Kimberley D

    2013-10-01

    The purpose of this study is to report psychometric properties of scores obtained using a novel observer-rated measure of children's self-regulation, the Response to Challenge Scale (RCS). The RCS was developed to rate children's self-regulatory abilities in a physically active context (e.g., while completing a physical challenge course). The RCS and other study measures were administered in a private school sample of 207 children. Analyses of score distributions indicated that the RCS was able to capture variance among children in self-regulatory abilities; the distribution was normal for the Affective, Cognitive, and Total Self-Regulation scales. Validity analyses revealed significant positive correlations between Cognitive, Affective, Motor, and Total Self-Regulation and executive function task performance; significant negative correlations between Cognitive Regulation and teacher-rated hyperactivity and inattention; significant negative correlations between Affective, Motor, and Total Self-Regulation and teacher ratings of peer problems; and significant positive correlations between Cognitive and Affective Regulation and parent ratings of prosocial behavior. Parent and teacher rated Total Difficulties scores were both negatively correlated with RCS Total Self-Regulation scores. Results suggest that it is possible for observers to rate self-regulatory abilities in the context of physical activities, and that these ratings correspond with performance on tasks requiring executive function as well as teacher and parent ratings of children's difficulties.

  18. OXPHOS-Mediated Induction of NAD+ Promotes Complete Oxidation of Fatty Acids and Interdicts Non-Alcoholic Fatty Liver Disease.

    PubMed

    Akie, Thomas E; Liu, Lijun; Nam, Minwoo; Lei, Shi; Cooper, Marcus P

    2015-01-01

    OXPHOS is believed to play an important role in non-alcoholic fatty liver disease (NAFLD), however, precise mechanisms whereby OXPHOS influences lipid homeostasis are incompletely understood. We previously reported that ectopic expression of LRPPRC, a protein that increases cristae density and OXPHOS, promoted fatty acid oxidation in cultured primary hepatocytes. To determine the biological significance of that observation and define underlying mechanisms, we have ectopically expressed LRPPRC in mouse liver in the setting of NAFLD. Interestingly, ectopic expression of LRPPRC in mouse liver completely interdicted NAFLD, including inflammation. Consistent with mitigation of NAFLD, two markers of hepatic insulin resistance--ROS and PKCε activity--were both modestly reduced. As reported by others, improvement of NAFLD was associated with improved whole-body insulin sensitivity. Regarding hepatic lipid homeostasis, the ratio of NAD+ to NADH was dramatically increased in mouse liver replete with LRPPRC. Pharmacological activators and inhibitors of the cellular respiration respectively increased and decreased the [NAD+]/[NADH] ratio, indicating respiration-mediated control of the [NAD+]/[NADH] ratio. Supporting a prominent role for NAD+, increasing the concentration of NAD+ stimulated complete oxidation of fatty acids. Importantly, NAD+ rescued impaired fatty acid oxidation in hepatocytes deficient for either OXPHOS or SIRT3. These data are consistent with a model whereby augmented hepatic OXPHOS increases NAD+, which in turn promotes complete oxidation of fatty acids and protects against NAFLD.

  19. A Polygenic Risk Score of glutamatergic SNPs associated with schizophrenia predicts attentional behavior and related brain activity in healthy humans.

    PubMed

    Rampino, Antonio; Taurisano, Paolo; Fanelli, Giuseppe; Attrotto, Mariateresa; Torretta, Silvia; Antonucci, Linda Antonella; Miccolis, Grazia; Pergola, Giulio; Ursini, Gianluca; Maddalena, Giancarlo; Romano, Raffaella; Masellis, Rita; Di Carlo, Pasquale; Pignataro, Patrizia; Blasi, Giuseppe; Bertolino, Alessandro

    2017-09-01

    Multiple genetic variations impact on risk for schizophrenia. Recent analyses by the Psychiatric Genomics Consortium (PGC2) identified 128 SNPs genome-wide associated with the disorder. Furthermore, attention and working memory deficits are core features of schizophrenia, are heritable and have been associated with variation in glutamatergic neurotransmission. Based on this evidence, in a sample of healthy volunteers, we used SNPs associated with schizophrenia in PGC2 to construct a Polygenic-Risk-Score (PRS) reflecting the cumulative risk for schizophrenia, along with a Polygenic-Risk-Score including only SNPs related to genes implicated in glutamatergic signaling (Glu-PRS). We performed Factor Analysis for dimension reduction of indices of cognitive performance. Furthermore, both PRS and Glu-PRS were used as predictors of cognitive functioning in the domains of Attention, Speed of Processing and Working Memory. The association of the Glu-PRS on brain activity during the Variable Attention Control (VAC) task was also explored. Finally, in a second independent sample of healthy volunteers we sought to confirm the association between the Glu-PRS and both performance in the domain of Attention and brain activity during the VAC.We found that performance in Speed of Processing and Working Memory was not associated with any of the Polygenic-Risk-Scores. The Glu-PRS, but not the PRS was associated with Attention and brain activity during the VAC. The specific effects of Glu-PRS on Attention and brain activity during the VAC were also confirmed in the replication sample.Our results suggest a pathway specificity in the relationship between genetic risk for schizophrenia, the associated cognitive dysfunction and related brain processing. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  20. Steroidogenic acute regulatory protein (StAR) overexpression attenuates HFD-induced hepatic steatosis and insulin resistance.

    PubMed

    Qiu, Yanyan; Sui, Xianxian; Zhan, Yongkun; Xu, Chen; Li, Xiaobo; Ning, Yanxia; Zhi, Xiuling; Yin, Lianhua

    2017-04-01

    Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology. Intracellular lipid accumulation is the first step in the development and progression of NAFLD. Steroidogenic acute regulatory protein (StAR) plays an important role in the synthesis of bile acid and intracellular lipid homeostasis and cholesterol metabolism. We hypothesize that StAR is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. The hypothesis was identified using free fatty acid (FFA)-overloaded NAFLD in vitro model and high-fat diet (HFD)-induced NAFLD mouse model transfected by recombinant adenovirus encoding StAR (StAR). StAR expression was also examined in pathology samples of patients with fatty liver by immunohistochemical staining. We found that the expression level of StAR was reduced in the livers obtained from fatty liver patients and NAFLD mice. Additionally, StAR overexpression decreased the levels of hepatic lipids and maintained the hepatic glucose homeostasis due to the activation of farnesoid x receptor (FXR). StAR overexpression attenuated the impairment of insulin signaling in fatty liver. This protective role of StAR was owing to a reduction of intracellular diacylglycerol levels and the phosphorylation of PKCε. Furthermore, FXR inactivation reversed the observed beneficial effects of StAR. The present study revealed that StAR overexpression can reduce hepatic lipid accumulation, regulate glucose metabolism and attenuate insulin resistance through a mechanism involving the activation of FXR. Our study suggests that StAR may be a potential therapeutic target for NAFLD. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Care standards for non-alcoholic fatty liver disease in the United Kingdom 2016: a cross-sectional survey.

    PubMed

    Sheridan, David A; Aithal, Guru; Alazawi, William; Allison, Michael; Anstee, Quentin; Cobbold, Jeremy; Khan, Shahid; Fowell, Andrew; McPherson, Stuart; Newsome, Philip N; Oben, Jude; Tomlinson, Jeremy; Tsochatzis, Emmanouil

    2017-10-01

    Guidelines for the assessment of non-alcoholic fatty liver disease (NAFLD) have been published in 2016 by National Institute for Health and Care Excellence and European Associations for the study of the Liver-European Association for the study of Diabetes-European Association for the study of Obesity. Prior to publication of these guidelines, we performed a cross-sectional survey of gastroenterologists and hepatologists regarding NAFLD diagnosis and management. An online survey was circulated to members of British Association for the Study of the Liver and British Society of Gastroenterology between February 2016 and May 2016. 175 gastroenterologists/hepatologists responded, 116 completing the survey, representing 84 UK centres. 22% had local NAFLD guidelines. 45% received >300 referrals per year from primary care for investigation of abnormal liver function tests (LFTs). Clinical assessment tended to be performed in secondary rather than primary care including body mass index (82% vs 26%) and non-invasive liver screen (86% vs 32%) and ultrasound (81% vs 37%). Widely used tools for non-invasive fibrosis risk stratification were aspartate transaminase (AST)/alanine transaminase (ALT) ratio (53%), Fibroscan (50%) and NAFLD fibrosis score (41%). 78% considered liver biopsy in selected cases. 50% recommended 10% weight loss target as first-line treatment. Delivery of lifestyle interventions was mostly handed back to primary care (56%). A minority have direct access to community weight management services (22%). Follow-up was favoured by F3/4 fibrosis (72.9%), and high-risk non-invasive fibrosis tests (51%). Discharge was favoured by simple steatosis at biopsy (30%), and low-risk non-invasive scores (25%). The survey highlights areas for improvement of service provision for NAFLD assessment including improved recognition of non-alcoholic steatohepatitis in people with type 2 diabetes, streamlining abnormal LFT referral pathways, defining non-invasive liver fibrosis

  2. Progression of liver fibrosis is associated with non‐liver‐related mortality in patients with nonalcoholic fatty liver disease

    PubMed Central

    Kumada, Takashi; Toyoda, Hidenori; Mizuno, Kazuyuki; Sone, Yasuhiro; Akita, Tomoyuki; Tanaka, Junko

    2017-01-01

    In patients with nonalcoholic fatty liver disease (NAFLD), prognosis and outcome, especially non‐liver‐related mortality, remain incompletely elucidated. We clarified the mortality from all causes in patients with NAFLD. A total of 4,073 patients with NAFLD diagnosed by ultrasonography were enrolled. We investigated the causes of death and analyzed the mortality from non‐liver‐related diseases according to the degrees of steatosis and fibrosis using the competing risk method. We used the NAFLD fibrosis score (NFS) to assess fibrosis severity and the ultrasonography fatty liver score to evaluate steatosis severity. The numbers of patients with NFS indicating low, intermediate, and high probabilities of advanced fibrosis were 2,451 (60.2%), 1,462 (35.9%), and 160 (3.9%), respectively. Of the 4,073 patients, 179 died during follow‐up, but only nine deaths were due to liver‐related diseases. Of the remaining 170 patients who died due to non‐liver‐related diseases, 83 (48.8%), 42 (24.7%), and 45 (26.5%) patients died due to malignancies, cerebrovascular and cardiovascular diseases, and benign diseases (excluding cerebrovascular and cardiovascular diseases), respectively. Multivariate analysis showed that the intermediate and high NFS groups were independently associated with each disease category: hazard ratio (HR) 2.163 (95% confidence interval [CI], 1.354‐3.457) and HR 4.814 (95% CI, 2.323‐9.977) for malignancies; HR 2.265 (95% CI, 1.141‐4.497) and HR 8.482 (95% CI, 3.558‐20.220) for cerebrovascular and cardiovascular diseases; and HR 3.216 (95% CI, 1.641‐6.303) and HR 5.558 (95% CI, 1.923‐16.070) for benign diseases, respectively. Conversely, the status of steatosis was not associated with risk of mortality in multivariate analysis. Conclusion: Progression of liver fibrosis severity was associated with mortality from various non‐liver‐related causes in patients with NAFLD. (Hepatology Communications 2017;1:928–945) PMID:29404500

  3. In vivo efficacy study of milk thistle extract (ETHIS-094™) in STAM™ model of nonalcoholic steatohepatitis.

    PubMed

    Pais, Pilar; D'Amato, Massimo

    2014-12-01

    A subcategory of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is characterized by accumulation of fat accompanied by inflammatory infiltration and hepatocellular damage. The active complex of milk thistle is a lipophilic extract from its seeds, comprising three isomers, collectively known as silymarin. Silymarin has demonstrated antioxidant, anti-inflammatory, and antifibrotic properties, and has been extensively studied in the treatment of liver diseases. The majority of published clinical research on silymarin has used Legalon(®) (Rottapharm/Madaus), containing the patented extract of milk thistle ETHIS-094™ (Euromed). The current study was undertaken to examine the effects of ETHIS-094™ in the Stelic Animal Model (STAM™), a validated and widely used animal model for NASH. After 4 h fasting from 4 to 8 weeks of age, 15 male mice in whom NASH had been induced were orally administered, once daily, either (1) vehicle (saline) at a volume of 10 mL/kg, (2) vehicle supplemented with milk thistle at a dose of 500 mg/kg, or (3) vehicle supplemented with milk thistle at a dose of 1,000 mg/kg. Mean liver weight and the liver-to-body weight ratio were significantly (P < 0.01) decreased in the milk thistle high-dose group compared with the vehicle group. NAFLD activity score (NAS) tended to decrease in the milk thistle treatment groups compared with vehicle group, as did steatosis scores. Milk thistle extract administration induced a decreasing trend in NAS compared with the vehicle group. Milk thistle induced a numerical decrease of the steatosis score compared with vehicle, and this was accompanied by a statistically significant decrease in liver weight and the liver-to-body weight ratio, implying a potential anti-steatosis effect of milk thistle.

  4. Screening for therapeutic trials and treatment indication in clinical practice: MACK-3, a new blood test for the diagnosis of fibrotic NASH.

    PubMed

    Boursier, J; Anty, R; Vonghia, L; Moal, V; Vanwolleghem, T; Canivet, C M; Michalak, S; Bonnafous, S; Michielsen, P; Oberti, F; Iannelli, A; Van Gaal, L; Patouraux, S; Blanchet, O; Verrijken, A; Gual, P; Rousselet, M-C; Driessen, A; Hunault, G; Bertrais, S; Tran, A; Calès, P; Francque, S

    2018-05-01

    The composite histological endpoint comprising nonalcoholic steatohepatitis (NASH) and NAFLD activity score ≥4 and advanced fibrosis (F ≥ 2) ("fibrotic NASH") is becoming an important diagnostic target in NAFLD: it is currently used to select patients for inclusion in phase III therapeutic trials and will ultimately be used to indicate treatment in clinical practice once the new drugs are approved. To develop a new blood test specifically dedicated for this new diagnostic target of interest. Eight Hundred and forty-six biopsy-proven NAFLD patients from three centres (Angers, Nice, Antwerp) were randomised into derivation and validation sets. The blood fibrosis tests BARD, NFS and FIB4 had poor accuracy for fibrotic NASH with respective AUROC: 0.566 ± 0.023, 0.654 ± 0.023, 0.732 ± 0.021. In the derivation set, fibrotic NASH was independently predicted by AST, HOMA and CK18; all three were combined in the new blood test MACK-3 (hoMa, Ast, CK18) for which 90% sensitivity and 95% specificity cut-offs were calculated. In the validation set, MACK-3 had a significantly higher AUROC (0.847 ± 0.030, P ≤ 0.002) than blood fibrosis tests. Using liver biopsy in the grey zone between the two cut-offs (36.0% of the patients), MACK-3 provided excellent accuracy for the diagnosis of fibrotic NASH with 93.3% well-classified patients, sensitivity: 90.0%, specificity: 94.2%, positive predictive value: 81.8% and negative predictive value: 97.0%. The new blood test MACK-3 accurately diagnoses fibrotic NASH. This new test will facilitate patient screening and inclusion in NAFLD therapeutic trials and will enable the identification of patients who will benefit from the treatments once approved. © 2018 John Wiley & Sons Ltd.

  5. Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats.

    PubMed

    Ji, Chenlin; Dai, Yanyan; Jiang, Weiwei; Liu, Juan; Hou, Miao; Wang, Junle; Burén, Jonas; Li, Xiaonan

    2014-11-01

    Exposure to overnutrition in critical or sensitive developmental periods may increase the risk of developing obesity and metabolic syndrome in adults. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, but the relationship among postnatal nutrition, lipid metabolism, and NAFLD progression during development remains poorly understood. Here we investigated in a rat model whether postnatal overfeeding increases susceptibility to NAFLD in response to a high-fat diet. Litters from Sprague-Dawley dams were culled to three (small litters) or ten (normal litters) pups and then weaned onto a standard or high-fat diet at postnatal day 21 to generate normal-litter, small-litter, normal-litter/high-fat, and small-litter/high-fat groups. At age 16 weeks, the small-litter and both high-fat groups showed obesity, dyslipidemia, and insulin resistance. Hepatic disorders appeared earlier in the small-litter/high-fat rats with greater liver mass gain and higher hepatic triglycerides and steatosis score versus normal-litter/high-fat rats. Hepatic acetyl-CoA carboxylase activity and mRNA expression were increased in small-litter rats and aggravated in small-litter/high-fat rats but not in normal-litter/high-fat rats. The high expression in small-litter/high-fat rats coincided with high sterol regulatory element-binding protein-1c mRNA and protein expression. However, mRNA expression of enzymes involved in hepatic fatty acid oxidation (carnitine palmitoyltransferase 1) and output (microsomal triglyceride transfer protein) was decreased under a high-fat diet regardless of litter size. In conclusion, overfeeding related to small-litter rearing during lactation contributes to the NAFLD phenotype when combined with a high-fat diet, possibly through up-regulated hepatic lipogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease.

    PubMed

    Boursier, Jérôme; Vergniol, Julien; Guillet, Anne; Hiriart, Jean-Baptiste; Lannes, Adrien; Le Bail, Brigitte; Michalak, Sophie; Chermak, Faiza; Bertrais, Sandrine; Foucher, Juliette; Oberti, Frédéric; Charbonnier, Maude; Fouchard-Hubert, Isabelle; Rousselet, Marie-Christine; Calès, Paul; de Lédinghen, Victor

    2016-09-01

    NAFLD is highly prevalent but only a small subset of patients develop advanced liver fibrosis with impaired liver-related prognosis. We aimed to compare blood fibrosis tests and liver stiffness measurement (LSM) by FibroScan for the diagnosis of liver fibrosis and the evaluation of prognosis in NAFLD. Diagnostic accuracy was evaluated in a cross-sectional study including 452 NAFLD patients with liver biopsy (NASH-CRN fibrosis stage), LSM, and eight blood fibrosis tests (BARD, NAFLD fibrosis score, FibroMeter(NAFLD), aspartate aminotransferase to platelet ratio index (APRI), FIB4, FibroTest, Hepascore, FibroMeter(V2G)). Prognostic accuracy was evaluated in a longitudinal study including 360 NAFLD patients. LSM and FibroMeter(V2G) were the two best-performing tests in the cross-sectional study: AUROCs for advanced fibrosis (F3/4) were, respectively, 0.831±0.019 and 0.817±0.020 (p⩽0.041 vs. other tests); rates of patients with ⩾90% negative/positive predictive values for F3/4 were 56.4% and 46.7% (p<0.001 vs. other tests); Obuchowski indexes were 0.834±0.014 and 0.798±0.016 (p⩽0.036 vs. other tests). Two fibrosis classifications were developed to precisely estimate the histological fibrosis stage from LSM or FibroMeter(V2G) results without liver biopsy (diagnostic accuracy, respectively: 80.8% vs. 77.4%, p=0.190). Kaplan-Meier curves in the longitudinal study showed that both classifications categorised NAFLD patients into subgroups with significantly different prognoses (p<0.001): the higher was the class of the fibrosis classification, the worse was the prognosis. LSM and FibroMeter(V2G) were the most accurate of nine evaluated tests for the non-invasive diagnosis of liver fibrosis in NAFLD. LSM and FibroMeter(V2G) fibrosis classifications help physicians estimate both fibrosis stage and patient prognosis in clinical practice. The amount of liver fibrosis is the main determinant of the liver-related prognosis in patients with non-alcoholic fatty liver

  7. Prognostic Value of Non-Invasive Fibrosis and Steatosis Tools, Hepatic Venous Pressure Gradient (HVPG) and Histology in Nonalcoholic Steatohepatitis.

    PubMed

    Sebastiani, Giada; Alshaalan, Rasha; Wong, Philip; Rubino, Maria; Salman, Ayat; Metrakos, Peter; Deschenes, Marc; Ghali, Peter

    2015-01-01

    Non-invasive diagnostic methods for liver fibrosis predict clinical outcomes in viral hepatitis and nonalcoholic fatty liver disease (NAFLD). We specifically evaluated prognostic value of non-invasive fibrosis methods in nonalcoholic steatohepatitis (NASH) against hepatic venous pressure gradient (HVPG) and liver histology. This was a retrospective cohort study of 148 consecutive patients who met the following criteria: transjugular liver biopsy with HVPG measurement; biopsy-proven NASH; absence of decompensation; AST-to-Platelets Ratio Index (APRI), fibrosis-4 (FIB-4), NAFLD fibrosis score, ultrasound, hepatic steatosis index and Xenon-133 scan available within 6 months from biopsy; a minimum follow-up of 1 year. Outcomes were defined by death, liver transplantation, cirrhosis complications. Kaplan-Meier and Cox regression analyses were employed to estimate incidence and predictors of outcomes, respectively. Prognostic value was expressed as area under the curve (AUC). During a median follow-up of 5 years (interquartile range 3-8), 16.2% developed outcomes, including 7.4% who died or underwent liver transplantation. After adjustment for age, sex, diabetes, the following fibrosis tools predicted outcomes: HVPG >10mmHg (HR=9.60; 95% confidence interval [CI] 3.07-30.12), histologic fibrosis F3-F4 (HR=3.14; 1.41-6.95), APRI >1.5 (HR=5.02; 1.6-15.7), FIB-4 >3.25 (HR=6.33; 1.98-20.2), NAFLD fibrosis score >0.676 (HR=11.9; 3.79-37.4). Prognostic value was as follows: histologic fibrosis stage, AUC=0.85 (95% CI 0.76-0.93); HVPG, AUC=0.81 (0.70-0.91); APRI, AUC=0.89 (0.82-0.96); FIB-4, AUC=0.89 (0.83-0.95); NAFLD fibrosis score, AUC=0.79 (0.69-0.91). Neither histologic steatosis nor non-invasive steatosis methods predicted outcomes (AUC<0.50). Non-invasive methods for liver fibrosis predict outcomes of patients with NASH. They could be used for serial monitoring, risk stratification and targeted interventions.

  8. A Comparison of Self-Report Scales and Accelerometer-Determined Moderate to Vigorous Physical Activity Scores of Finnish School Students

    ERIC Educational Resources Information Center

    Gråstén, Arto; Watt, Anthony

    2016-01-01

    The current article provides an important insight into measurement differences between two commonly used self-reports and accelerometer-determined moderate to vigorous physical activity (MVPA) scores within matched samples across 1 school year. Participants were 998 fifth- through eighth-grade students who completed self-reports and 76 fifth- and…

  9. Prevalence, risk factors, and predictors of nonalcoholic fatty liver disease among schoolchildren: a hospital-based study in Alexandria, Egypt.

    PubMed

    Alkassabany, Yasmine M; Farghaly, Azza G; El-Ghitany, Engy M

    2014-06-01

    Nonalcoholic fatty liver disease (NAFLD) is an emerging problem in children and adolescents worldwide. This study was done to investigate the prevalence of NAFLD in children and adolescents as well as to determine the associated risk factors of fatty liver and to explore the ability of some obesity indices to predict and consequently be used as a screening method of fatty liver disease at certain cutoff points in schoolchildren. A cross-sectional, nested case-control study was carried out. Cases and controls were randomly selected from outpatient schoolchildren aged 6-18years attending the radiology clinic at Sporting Health Insurance Paediatric Hospital in Alexandria. They were subjected to ultrasonic examination as well as complete anthropometric and laboratory measurements including fasting plasma glucose (FPG) level, fasting insulin, alanine aminotransferase (ALT) level, and lipid profile. Fatty liver was prevalent in schoolchildren (15.8%) and increased significantly with age (p=0.004). Positive family history of diabetes mellitus (DM), hypertension (HTN), obesity, and liver disease were all statistically significant risk factors for fatty liver. Waist circumference (WC), body mass index (BMI) and its Z-score were significantly sensitive predictors. BMI was considered the best predictor of paediatric NAFLD at a cutoff=22.9. NAFLD was significantly associated with high triglycerides (TGs), low high-density lipoprotein cholesterol (HDL), homoeostatic model assessment (HOMA) percentile, and the number of metabolic syndrome (MS) components. Paediatric NAFLD is a substantial problem in schoolchildren and has a close relationship with obesity, dyslipidaemia, insulin resistance (IR), and consequently MS. BMI and WC can be used as useful predictors and screening tools for NAFLD in schoolchildren. Copyright © 2014 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

  10. Nonalcoholic fatty liver disease in long-term survivors of childhood-onset craniopharyngioma.

    PubMed

    Jung, So Yoon; Lee, Yun Jeong; Lee, Hye Jin; Lee, Young Ah; Moon, Jin Soo; Ko, Jae Sung; Yang, Sei Won; Shin, Choong Ho

    2017-09-01

    Hypothalamic obesity in childhood-onset (CO-) craniopharyngioma patients may predispose to nonalcoholic fatty liver disease (NAFLD). This study reviewed the characteristics of NAFLD associated with CO-craniopharyngioma. This study retrospectively reviewed 75 patients who underwent surgery for craniopharyngioma while younger than 15 years of age between 2000 and 2016. Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 40 IU/L was observed in 51 of the 75 (68%) CO-craniopharyngioma patients. Imaging studies were performed in 32 patients with elevated liver enzymes. The estimated prevalence of NAFLD in CO-craniopharyngioma was 47%. NAFLD was detected in 22 patients (male 59%, 4.3±4.0 years after first surgery). The mean age at the time of the initial operation was 9.1±2.9 years. Six patients (27.3%) were diagnosed within 1 year. Among the 19 patients with initial height and weight data, the body mass index (BMI) z-score (BMI_Z) at the time of diagnosis with NAFLD was 1.37±1.01 (range, -0.75 to 3.18), with 4 patients (18.2%) being overweight and 9 (40.9%) being obese. BMI_Z increased above BMI_Z at the time of the operation in 13 patients (68.4%). The increment in BMI_Z was 1.13 (range, 0.10-2.84). Seventeen patients did not receive growth hormone. An insulin-like growth factor-I level <3rd percentile was observed in 19 patients. NAFLD is common in survivors of CO-craniopharyngioma and may develop earlier. If the ALT or AST is above 40 IU/L, a diagnostic work-up should be started.

  11. Lifestyle Interventions including Nutrition, Exercise, and Supplements for Nonalcoholic Fatty Liver Disease in Children

    PubMed Central

    Africa, Jonathan A.; Newton, Kimberly P.; Schwimmer, Jeffrey B.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease among children. Lifestyle interventions, such as diet and exercise, are frequently recommended. Children with NAFLD have a distinct physiology that is different from obesity alone and has the potential to influence lifestyle treatments. Studies of diet alone in the treatment of pediatric NAFLD have focused on sugar and carbohydrate, but did not indicate any one dietary approach that was superior to another. For children who are obese and have NAFLD, weight loss may have a beneficial effect regardless of the diet used. Exercise is widely believed to improve NAFLD because a sedentary lifestyle, poor aerobic fitness, and low muscle mass are all risk factors for NAFLD. However, there have been no randomized controlled trials of exercise as a treatment for children with NAFLD. Studies of the combination of diet and exercise suggest a potential for improvement in serum alanine aminotransferase activity and/or magnetic resonance imaging liver fat fraction with intervention. There is also enthusiasm for the use of dietary supplements, however, studies in children have shown inconsistent effects of vitamin E, fish oil, and probiotics. This review presents the available data from studies of lifestyle intervention and dietary supplements published to date, and highlights challenges that must be addressed in order to advance the evidence base for the treatment of pediatric NAFLD. PMID:27041377

  12. Efficacy of Probiotics and Smectite in Rats with Non-Alcoholic Fatty Liver Disease.

    PubMed

    Kobyliak, Nazarii; Abenavoli, Ludovico; Falalyeyeva, Tetyana; Beregova, Tetyana

    2018-01-01

    Today probiotics have been suggested as a treatment for the prevention of non-alcoholic fatty liver disease (NAFLD). Smectite is a natural silicate that binds to digestive mucous and has the ability to bind endo- and exotoxins. The present study was designed to determine whether probiotics plus smectite is superior to probiotic alone on the monosodium glutamate (MSG) induced NAFLD model in rats. We included 60 rats divided into 4 groups 15 animals in each. Rats of group I were intact. Newborns rats of groups II-IV were injected with MSG. The III (Symbiter) group received 2.5 ml/kg of multiprobiotic "Symbiter" containing concentrated biomass of 14 probiotic bacteria genera. The IV (Symbiter+Smectite) groups received "Symbiter Forte" combination of probiotic biomass with smectite gel (250 mg). In both interventional groups reduction of total NAS score as compared to MSG-obesity was observed. Indeed similar values of steatosis score (0.93 ± 0.22 vs. 0.87 ± 0.16) in both treatment groups, we observed that lower total score for Symbiter+ Smectite are associated with more pronounced reduction of lobular inflammation (0.13 ± 0.09 vs. 0.33 ± 0.15) as compared to administration of probiotic alone. This data accompanied with significant reduction of IL-1 and restoration of IL-10 between these 2 groups. Additional to alive probiotic administration of smectite gel due to his absorbent activity and mucus layer stabilization properties can impact on synergistic enhancement of single effect which manifested with reduction of lobular inflammation and at list partly steatohepatitis prevention.

  13. Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries

    PubMed Central

    Lückhoff, Hilmar K; Kruger, Frederik C; Kotze, Maritha J

    2015-01-01

    Heterogeneity in clinical presentation, histological severity, prognosis and therapeutic outcomes characteristic of non-alcoholic fatty liver disease (NAFLD) necessitates the development of scientifically sound classification schemes to assist clinicians in stratifying patients into meaningful prognostic subgroups. The need for replacement of invasive liver biopsies as the standard method whereby NAFLD is diagnosed, graded and staged with biomarkers of histological severity injury led to the development of composite prognostic models as potentially viable surrogate alternatives. In the present article, we review existing scoring systems used to (1) confirm the presence of undiagnosed hepatosteatosis; (2) distinguish between simple steatosis and NASH; and (3) predict advanced hepatic fibrosis, with particular emphasis on the role of NAFLD as an independent cardio-metabolic risk factor. In addition, the incorporation of functional genomic markers and application of emerging imaging technologies are discussed as a means to improve the diagnostic accuracy and predictive performance of promising composite models found to be most appropriate for widespread clinical adoption. PMID:26019735

  14. A Genomic Score Prognostic of Outcome in Trauma Patients

    PubMed Central

    Warren, H Shaw; Elson, Constance M; Hayden, Douglas L; Schoenfeld, David A; Cobb, J Perren; Maier, Ronald V; Moldawer, Lyle L; Moore, Ernest E; Harbrecht, Brian G; Pelak, Kimberly; Cuschieri, Joseph; Herndon, David N; Jeschke, Marc G; Finnerty, Celeste C; Brownstein, Bernard H; Hennessy, Laura; Mason, Philip H; Tompkins, Ronald G

    2009-01-01

    Traumatic injuries frequently lead to infection, organ failure, and death. Health care providers rely on several injury scoring systems to quantify the extent of injury and to help predict clinical outcome. Physiological, anatomical, and clinical laboratory analytic scoring systems (Acute Physiology and Chronic Health Evaluation [APACHE], Injury Severity Score [ISS]) are utilized, with limited success, to predict outcome following injury. The recent development of techniques for measuring the expression level of all of a person’s genes simultaneously may make it possible to develop an injury scoring system based on the degree of gene activation. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. To test such a scoring system, we measured gene expression of peripheral blood leukocytes from patients within 12 h of traumatic injury. cRNA derived from whole blood leukocytes obtained within 12 h of injury provided gene expression data for the entire genome that were used to create a composite gene expression score for each patient. Total blood leukocytes were chosen because they are active during inflammation, which is reflective of poor outcome. The gene expression score combines the activation levels of all the genes into a single number which compares the patient’s gene expression to the average gene expression in uninjured volunteers. Expression profiles from healthy volunteers were averaged to create a reference gene expression profile which was used to compute a difference from reference (DFR) score for each patient. This score described the overall genomic response of patients within the first 12 h following severe blunt trauma. Regression models were used to compare the association of the DFR, APACHE, and ISS scores with outcome. We hypothesized that patients with a total gene response more different from uninjured volunteers would tend to have poorer

  15. Higher association of coronary artery calcification with non-alcoholic fatty liver disease than with abdominal obesity in middle-aged Korean men: the Kangbuk Samsung Health Study.

    PubMed

    Lee, Min-Kyung; Park, Hye-Jeong; Jeon, Won Seon; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

    2015-07-15

    It is uncertain whether non-alcoholic fatty liver disease (NAFLD) or abdominal obesity is more associated with atherosclerosis. The aim of this study was to determine whether NAFLD or abdominal obesity is more strongly associated with subclinical atherosclerosis represented by coronary artery calcification (CAC). A total of 21,335 male participants in a health screening program (mean age 41 years) were enrolled. Ultrasonographic measurements of fatty liver and multi-detector computed tomography were performed to determine the coronary artery calcium score (CACS). The presence of CAC was defined as CACS > 0. Subjects were divided into four groups according to the presence or absence of NAFLD and/or abdominal obesity as assessed by waist-hip ratio (WHR) > 0.9. The presence of CAC was detected in 2,385 subjects (11.2%). The proportion of subjects with CAC was highest in the abdominal obesity only group (23.2%). After adjustment for age, diabetes history, hypertension, cigarette smoking, and physical inactivity, the odds ratio (OR) for CAC was the highest in the group with both abnormalities [1.465 (1.324-1.623)]. The NAFLD only group showed significantly increased OR for CAC compared to that in the abdominal obesity only group [1.286 (1.151-1.436) vs. 1.076 (0.939-1.233)]. Non-alcoholic fatty liver disease is more closely associated with CAC than abdominal obesity as assessed by the WHR. NAFLD could be considered an independent determinant of subclinical atherosclerosis as assessed by CAC.

  16. Automated large-scale file preparation, docking, and scoring: evaluation of ITScore and STScore using the 2012 Community Structure-Activity Resource benchmark.

    PubMed

    Grinter, Sam Z; Yan, Chengfei; Huang, Sheng-You; Jiang, Lin; Zou, Xiaoqin

    2013-08-26

    In this study, we use the recently released 2012 Community Structure-Activity Resource (CSAR) data set to evaluate two knowledge-based scoring functions, ITScore and STScore, and a simple force-field-based potential (VDWScore). The CSAR data set contains 757 compounds, most with known affinities, and 57 crystal structures. With the help of the script files for docking preparation, we use the full CSAR data set to evaluate the performances of the scoring functions on binding affinity prediction and active/inactive compound discrimination. The CSAR subset that includes crystal structures is used as well, to evaluate the performances of the scoring functions on binding mode and affinity predictions. Within this structure subset, we investigate the importance of accurate ligand and protein conformational sampling and find that the binding affinity predictions are less sensitive to non-native ligand and protein conformations than the binding mode predictions. We also find the full CSAR data set to be more challenging in making binding mode predictions than the subset with structures. The script files used for preparing the CSAR data set for docking, including scripts for canonicalization of the ligand atoms, are offered freely to the academic community.

  17. The association between physical activity, sedentary behavior, sleep, and body mass index z-scores in different settings among toddlers and preschoolers.

    PubMed

    Kuzik, Nicholas; Carson, Valerie

    2016-07-20

    Physical activity, sedentary behavior, and sleep are all movement behaviors that range on a continuum from no or low movement, to high movement. Consistent associations between movement behaviors and adiposity indicators have been observed in school-age children. However, limited information exists in younger children. Since approximately 50 % of Canadian children ≤5 years of age attend non-parental care, movement behaviors within and outside of the child care setting are important to consider. Therefore, this study examined the association between movement behaviors (physical activity, sedentary behavior and sleep) inside and outside of child care, with body mass index (BMI) z-scores, among a sample of toddlers and preschoolers. Children aged 19-60 months (n = 100) from eight participating child care centers throughout Alberta, Canada participated. Movement behaviors inside child care were accelerometer-derived (light physical activity, moderate to vigorous physical activity (MVPA), sedentary time, and time spent in sedentary bouts lasting 1-4, 5-9, 10-14 and ≥15 min) and questionnaire-derived (daytime sleep). Movement behaviors outside of child care were questionnaire-derived (MVPA, screen and non-screen sedentary behavior, and nighttime sleep). Demographic information (child age, child sex, and parental education) was also questionnaire-derived. Height and weight were measured, and age- and sex-specific BMI z-scores were calculated using World Health Organization growth standards. The association between movement behaviors and BMI z-scores were examined using linear regression models. Hours/day of sedentary bouts lasting 1-4 min (β =-0.8, 95 % CI:-1.5,-0.1) and nighttime sleep (β = 0.2, 95 % CI: 0.1, 0.4) were associated with BMI z-scores. However, after adjusting for demographics variables, sedentary bouts lasting 1-4 min (β =-0.7; 95 % CI:-1.5, 0.0) became borderline non-significant, while nighttime sleep (β = 0.2, 95 % CI: 0

  18. Secondhand tobacco exposure is associated with nonalcoholic fatty liver disease in children

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, Connie; Rountree, Carl B.; Department of Pediatrics, Bon Secour St. Mary's Hospital, 5801 Bremo Rd, Richmond, VA 23226

    Background: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in children in the United States, and prevalence rates are rising. Smoking is associated with NAFLD, but the association of secondhand smoke exposure with NAFLD is unknown. Aims: To investigate the association of secondhand tobacco exposure with NAFLD in children. Methods: We surveyed parents/guardians of 304 children aged 3–12 years who had received an abdominal ultrasound at Penn State Hershey Medical Center. The survey addressed demographics, medical history, secondhand tobacco exposure, activity level, screen viewing time and other environmental exposures. A pediatric radiologist and sonographer reviewed themore » ultrasounds to grade the presence of bight liver compatible with NAFLD. We conducted logistic regression analysis to assess the association of secondhand tobacco exposure and NAFLD. Results: 54% of eligible potential participants responded to the survey. Fatty liver was present in 3% of the children. Increasing child age was associated with increased odds of NAFLD (OR 1.63 95% CI 1.1, 2.4). Reported child obesity was associated with increased odds of NAFLD (OR 44.5 95% CI 5.3, 371.7). The rate of NAFLD was higher in the smoke exposed group (6.7% vs. 1.7%). For every extra pack per day smoked at home, the odds of a child having NAFLD increased 1.8 times (AOR 1.8, 95% CI 1.2, 2.8), and any exposure increased a child's odds of NAFLD four-fold (AOR 4.0, 95% CI 1.02, 15.8). Conclusion: We found an association of secondhand smoke exposure and NAFLD in children. This may represent an area for future prevention efforts. - Highlights: • We evaluated the relation of tobacco exposure with nonalcoholic fatty liver disease. • Tobacco smoke exposure was associated with nonalcoholic fatty liver disease. • Tobacco smoke exposure may be an addressable risk factor.« less

  19. D-score: a search engine independent MD-score.

    PubMed

    Vaudel, Marc; Breiter, Daniela; Beck, Florian; Rahnenführer, Jörg; Martens, Lennart; Zahedi, René P

    2013-03-01

    While peptides carrying PTMs are routinely identified in gel-free MS, the localization of the PTMs onto the peptide sequences remains challenging. Search engine scores of secondary peptide matches have been used in different approaches in order to infer the quality of site inference, by penalizing the localization whenever the search engine similarly scored two candidate peptides with different site assignments. In the present work, we show how the estimation of posterior error probabilities for peptide candidates allows the estimation of a PTM score called the D-score, for multiple search engine studies. We demonstrate the applicability of this score to three popular search engines: Mascot, OMSSA, and X!Tandem, and evaluate its performance using an already published high resolution data set of synthetic phosphopeptides. For those peptides with phosphorylation site inference uncertainty, the number of spectrum matches with correctly localized phosphorylation increased by up to 25.7% when compared to using Mascot alone, although the actual increase depended on the fragmentation method used. Since this method relies only on search engine scores, it can be readily applied to the scoring of the localization of virtually any modification at no additional experimental or in silico cost. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Altenusin, a Nonsteroidal Microbial Metabolite, Attenuates Nonalcoholic Fatty Liver Disease by Activating the Farnesoid X Receptor.

    PubMed

    Zheng, Zhihui; Zhao, Zanmei; Li, Shuqiang; Lu, Xinhua; Jiang, Mengxi; Lin, Jie; An, Yunqi; Xie, Yang; Xu, Meishu; Shen, Wenbin; Guo, Grace L; Huang, Yixian; Li, Song; Zhang, Xuexia; Xie, Wen

    2017-10-01

    Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease. The incidence of NAFLD has increased steadily due to its close association with the global epidemic of obesity and type 2 diabetes. However, there is no effective pharmacological therapy approved for NAFLD. Farnesoid X receptor (FXR), a member of the nuclear receptor subfamily, plays important roles in maintaining the homeostasis of bile acids, glucose, and lipids. FXR agonists have shown promise for the treatment of NAFLD. In this study, we report altenusin (2076A), a natural nonsteroidal fungal metabolite, as a novel selective agonist of FXR with an EC 50 value of 3.2 ± 0.2 μM. Administration of 2076A protected mice from high-fat diet (HFD)-induced obesity by reducing the body weight and fat mass by 22.9% and 50.0%, respectively. Administration of 2076A also decreased the blood glucose level from 178.3 ± 12.4 mg/dl to 116.2 ± 4.1 mg/dl and the serum insulin level from 1.4 ± 0.6 ng/dl to 0.4 ± 0.1 ng/dl. Moreover, 2076A treatment nearly reversed HFD-induced hepatic lipid droplet accumulation and macrovesicular steatosis. These metabolic effects were abolished in FXR knockout mice. Mechanistically, the metabolic benefits of 2076A might have been accounted for by the increased insulin sensitivity and suppression of genes that are involved in hepatic gluconeogenesis and lipogenesis. In summary, we have uncovered a new class of nonsteroidal FXR agonist that shows promise in treating NAFLD and the associated metabolic syndrome. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  1. The Membrane-bound O-Acyltransferase7 rs641738 Variant in Pediatric Nonalcoholic Fatty Liver Disease.

    PubMed

    Di Sessa, Anna; Umano, Giuseppina Rosaria; Cirillo, Grazia; Del Prete, Angela; Iacomino, Roberta; Marzuillo, Pierluigi; Giudice, Emanuele Miraglia Del

    2018-03-29

    The rs641738 polymorphism in the membrane-bound O-acyltransferase domain containing protein 7 (MBOAT7) gene has been associated with increased risk of nonalcoholic fatty liver disease (NAFLD). To investigate the association between the MBOAT7 rs641738 polymorphism and both hepatic steatosis and biochemical markers of liver damage and to evaluate the potential additive effect of this variant and the I148M patatin-like phospholipase domain-containing 3 (PNPLA3) and the rs58542926 transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms. One thousand and 2 obese children were genotyped for MBOAT7, PNPLA3, and TM6SF2 polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) and a genetic risk score from these polymorphisms were calculated. Carriers of the MBOAT7 T allele showed both higher alanine transaminase (ALT) (P = 0.004) and PNFI values (P = 0.04) than noncarriers. These findings were confirmed also for the carriers of the MBOAT7 T allele polymorphism with hepatic steatosis compared with noncarriers. A higher genetic risk score was associated with higher ALT (P = 0.011) and with an odds ratio (OR) to show elevated ALT of 3.4 (95% CI 1.3-5.5, P = 0.003). Patients belonging to genetic risk score 3 group had an OR to present steatosis of 2.6 (95% CI 1.43-4.83, P = 0.0018) compared with those belonging to lower genetic risk score group. We first demonstrated in childhood obesity the role of the MBOAT7 rs641738 variant on serum ALT and the combined effect of the MBOAT7, PNPLA3, and TM6SF2 variants on NAFLD risk. We also provided the first pediatric association of the MBOAT7 polymorphism with indirect markers of liver fibrosis.

  2. An external validation study reporting poor correlation between the claims-based index for rheumatoid arthritis severity and the disease activity score.

    PubMed

    Desai, Rishi J; Solomon, Daniel H; Weinblatt, Michael E; Shadick, Nancy; Kim, Seoyoung C

    2015-04-13

    We conducted an external validation study to examine the correlation of a previously published claims-based index for rheumatoid arthritis severity (CIRAS) with disease activity score in 28 joints calculated by using C-reactive protein (DAS28-CRP) and the multi-dimensional health assessment questionnaire (MD-HAQ) physical function score. Patients enrolled in the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and Medicare were identified and their data from these two sources were linked. For each patient, DAS28-CRP measurement and MD-HAQ physical function scores were extracted from BRASS, and CIRAS was calculated from Medicare claims for the period of 365 days prior to the DAS28-CRP measurement. Pearson correlation coefficient between CIRAS and DAS28-CRP as well as MD-HAQ physical function scores were calculated. Furthermore, we considered several additional pharmacy and medical claims-derived variables as predictors for DAS28-CRP in a multivariable linear regression model in order to assess improvement in the performance of the original CIRAS algorithm. In total, 315 patients with enrollment in both BRASS and Medicare were included in this study. The majority (81%) of the cohort was female, and the mean age was 70 years. The correlation between CIRAS and DAS28-CRP was low (Pearson correlation coefficient = 0.07, P = 0.24). The correlation between the calculated CIRAS and MD-HAQ physical function scores was also found to be low (Pearson correlation coefficient = 0.08, P = 0.17). The linear regression model containing additional claims-derived variables yielded model R(2) of 0.23, suggesting limited ability of this model to explain variation in DAS28-CRP. In a cohort of Medicare-enrolled patients with established RA, CIRAS showed low correlation with DAS28-CRP as well as MD-HAQ physical function scores. Claims-based algorithms for disease activity should be rigorously tested in distinct populations in order to establish

  3. Effect of Vitamin E or Metformin for Treatment of Nonalcoholic Fatty Liver Disease in Children and Adolescents

    PubMed Central

    Lavine, Joel E.; Schwimmer, Jeffrey B.; Van Natta, Mark L.; Molleston, Jean P.; Murray, Karen F.; Rosenthal, Philip; Abrams, Stephanie H.; Scheimann, Ann O.; Sanyal, Arun J.; Chalasani, Naga; Tonascia, James; Ünalp, Aynur; Clark, Jeanne M.; Brunt, Elizabeth M.; Kleiner, David E.; Hoofnagle, Jay H.; Robuck, Patricia R.

    2011-01-01

    Context Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in US children and adolescents and can present with advanced fibrosis or non-alcoholic steatohepatitis (NASH). No treatment has been established. Objective To determine whether children with NAFLD would improve from therapeutic intervention with vitamin E or metformin. Design, Setting, and Patients Randomized, double-blind, double-dummy, placebo-controlled clinical trial conducted at 10 university clinical research centers in 173 patients (aged 8–17 years) with biopsy-confirmed NAFLD conducted between September 2005 and March 2010. Interventions Daily dosing of 800 IU of vitamin E (58 patients), 1000 mg of metformin (57 patients), or placebo (58 patients) for 96 weeks. Main Outcome Measures The primary outcome was sustained reduction in alanine aminotransferase (ALT) defined as 50% or less of the baseline level or 40 U/L or less at visits every 12 weeks from 48 to 96 weeks of treatment. Improvements in histological features of NAFLD and resolution of NASH were secondary outcome measures. Results Sustained reduction in ALT level was similar to placebo (10/58; 17%; 95% CI, 9% to 29%) in both the vitamin E (15/58; 26%; 95% CI, 15% to 39%; P=.26) and metformin treatment groups (9/57; 16%; 95% CI, 7% to 28%; P=.83). The mean change in ALT level from baseline to 96 weeks was −35.2 U/L (95% CI, −56.9 to −13.5) with placebo vs −48.3 U/L (95% CI, −66.8 to −29.8) with vitamin E (P=.07) and −41.7 U/L (95% CI, −62.9 to −20.5) with metformin (P=.40). The mean change at 96 weeks in hepatocellular ballooning scores was 0.1 with placebo (95% CI, −0.2 to 0.3) vs −0.5 with vitamin E (95% CI, −0.8 to −0.3; P=.006) and −0.3 with metformin (95% CI, −0.6 to −0.0; P=.04); and in NAFLD activity score, −0.7 with placebo (95% CI, −1.3 to −0.2) vs −1.8 with vitamin E (95% CI, −2.4 to −1.2; P=.02) and −1.1 with metformin (95% CI, −1.7 to −0.5; P=.25

  4. Does Field Reliability for Static-99 Scores Decrease as Scores Increase?

    PubMed Central

    Rice, Amanda K.; Boccaccini, Marcus T.; Harris, Paige B.; Hawes, Samuel W.

    2015-01-01

    This study examined the field reliability of Static-99 (Hanson & Thornton, 2000) scores among 21,983 sex offenders and focused on whether rater agreement decreased as scores increased. As expected, agreement was lowest for high-scoring offenders. Initial and most recent Static-99 scores were identical for only about 40% of offenders who had been assigned a score of 6 during their initial evaluations, but for more than 60% of offenders who had been assigned a score of 2 or lower. In addition, the size of the difference between scores increased as scores increased, with pairs of scores differing by 2 or more points for about 30% of offenders scoring in the high-risk range. Because evaluators and systems use high Static-99 scores to identify sexual offenders who may require intensive supervision or even postrelease civil commitment, it is important to recognize that there may be more measurement error for high scores than low scores and to consider adopting procedures for minimizing or accounting for measurement error. PMID:24932647

  5. Non-alcoholic fatty liver disease induces signs of Alzheimer's disease (AD) in wild-type mice and accelerates pathological signs of AD in an AD model.

    PubMed

    Kim, Do-Geun; Krenz, Antje; Toussaint, Leon E; Maurer, Kirk J; Robinson, Sudie-Ann; Yan, Angela; Torres, Luisa; Bynoe, Margaret S

    2016-01-05

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease afflicting about one third of the world's population and 30 % of the US population. It is induced by consumption of high-lipid diets and is characterized by liver inflammation and subsequent liver pathology. Obesity and consumption of a high-fat diet are known to increase the risk of Alzheimer's disease (AD). Here, we investigated NAFLD-induced liver inflammation in the pathogenesis of AD. WT and APP-Tg mice were fed with a standard diet (SD) or a high-fat diet (HFD) for 2, 5 months, or 1 year to induce NAFLD. Another set of APP-Tg mice were removed from HFD after 2 months and put back on SD for 3 months. During acute phase NAFLD, WT and APP-Tg mice developed significant liver inflammation and pathology that coincided with increased numbers of activated microglial cells in the brain, increased inflammatory cytokine profile, and increased expression of toll-like receptors. Chronic NAFLD induced advanced pathological signs of AD in both WT and APP-Tg mice, and also induced neuronal apoptosis. We observed decreased brain expression of low-density lipoprotein receptor-related protein-1 (LRP-1) which is involved in β-amyloid clearance, in both WT and APP-Tg mice after ongoing administration of the HFD. LRP-1 expression correlated with advanced signs of AD over the course of chronic NAFLD. Removal of mice from HFD during acute NAFLD reversed liver pathology, decreased signs of activated microglial cells and neuro-inflammation, and decreased β-amyloid plaque load. Our findings indicate that chronic inflammation induced outside the brain is sufficient to induce neurodegeneration in the absence of genetic predisposition.

  6. Extension of the lod score: the mod score.

    PubMed

    Clerget-Darpoux, F

    2001-01-01

    In 1955 Morton proposed the lod score method both for testing linkage between loci and for estimating the recombination fraction between them. If a disease is controlled by a gene at one of these loci, the lod score computation requires the prior specification of an underlying model that assigns the probabilities of genotypes from the observed phenotypes. To address the case of linkage studies for diseases with unknown mode of inheritance, we suggested (Clerget-Darpoux et al., 1986) extending the lod score function to a so-called mod score function. In this function, the variables are both the recombination fraction and the disease model parameters. Maximizing the mod score function over all these parameters amounts to maximizing the probability of marker data conditional on the disease status. Under the absence of linkage, the mod score conforms to a chi-square distribution, with extra degrees of freedom in comparison to the lod score function (MacLean et al., 1993). The mod score is asymptotically maximum for the true disease model (Clerget-Darpoux and Bonaïti-Pellié, 1992; Hodge and Elston, 1994). Consequently, the power to detect linkage through mod score will be highest when the space of models where the maximization is performed includes the true model. On the other hand, one must avoid overparametrization of the model space. For example, when the approach is applied to affected sibpairs, only two constrained disease model parameters should be used (Knapp et al., 1994) for the mod score maximization. It is also important to emphasize the existence of a strong correlation between the disease gene location and the disease model. Consequently, there is poor resolution of the location of the susceptibility locus when the disease model at this locus is unknown. Of course, this is true regardless of the statistics used. The mod score may also be applied in a candidate gene strategy to model the potential effect of this gene in the disease. Since, however, it

  7. Hepatic FDG uptake is associated with future cardiovascular events in asymptomatic individuals with non-alcoholic fatty liver disease.

    PubMed

    Moon, Seung Hwan; Hong, Sun-Pyo; Cho, Young Seok; Noh, Tae Soo; Choi, Joon Young; Kim, Byung-Tae; Lee, Kyung-Han

    2017-06-01

    Hepatic F-18 fluoro-2-deoxyglucose (FDG) uptake is associated with non-alcoholic fatty liver disease (NAFLD) which is an independent risk factor for cardiovascular disease. However, the value of hepatic FDG uptake for predicting future cardiovascular events has not been explored. Study participants were 815 consecutive asymptomatic participants who underwent a health screening program that included FDG positron emission tomography/computed tomography (PET/CT), abdominal ultrasonography, and carotid intima-media thickness (CIMT) measurements (age 51.8 ± 6.0 year; males 93.9%). We measured hepatic FDG uptake and assessed the prognostic significance of this parameter with other cardiovascular risk factors including Framingham risk score and CIMT. Multivariate Cox proportional hazards analyses including all study participants revealed that NAFLD with high-hepatic FDG uptake was the only independent predictor for future cardiovascular events [hazard ratio (HR) 4.23; 95% CI 1.05-17.04; P = .043). Subgroup analysis conducted in the NAFLD group showed that high-hepatic FDG uptake was a significant independent predictor of cardiovascular events (HR 9.29; 95% CI 1.05-81.04; P = .045). This exploratory study suggests that high-hepatic FDG uptake may be a useful prognostic factor for cardiovascular events in individuals with NAFLD.

  8. Effect of a high monounsaturated vs high polyunsaturated fat hypocaloric diets in nonalcoholic fatty liver disease.

    PubMed

    Aller, R; de Luis, D A; Izaola, O; de la Fuente, B; Bachiller, R

    2014-01-01

    Hyperaminotransferasemia is an important problem in obese patients. We decide to examine the changes in hyperaminotransferasemia after weight reduction in obese patients with and without NAFLD secondary to a high monounsaturated fat vs. a high polyunsaturated fat hypocaloric diets. A population of 306 obese patients was randomly allocated to two groups: Diet M (high monounsaturated fat hypocaloric diet) and Diet P (high polyunsaturated fat hypocaloric diet). Patients were classified as group I (obese subjects; n=262) when serum ALT activity was normal or group II (NAFLD patients; n=44) when serum ALT activity was (≥ 43 UI/L). In NAFLD group with diet M, BMI, weight, fat mass, waist circumference, systolic blood pressure, total cholesterol, LDL cholesterol), insulin and HOMA-R decreased. In NAFLD group with diet P, BMI, weight, fat mass, waist circumference, systolic blood pressure, total cholesterol, LDL cholesterol), insulin and HOMA-R decreased, too. In NAFLD group, alanine aminotransferase [(diet M) -20.3±19.2 UI/L vs. (diet P) -14.2±20.1 UI/L], aspartate aminotransferase [(diet M) -11.3±12.2 UI/L vs. (diet P) -11.1±10.1 UI/L], and gammaglutamyl transferase [(diet M) -18.1±12.2 UI/L vs. (diet P) -10.9±20.1 UI/L] improved with both diets. We showed that weight reduction secondary to two hypocaloric diets was associated with improvement in hypertransaminasemia and insulin resistance in NAFLD patients.

  9. Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: Results from the WELCOME trial.

    PubMed

    Scorletti, Eleonora; West, Annette L; Bhatia, Lokpal; Hoile, Samuel P; McCormick, Keith G; Burdge, Graham C; Lillycrop, Karen A; Clough, Geraldine F; Calder, Philip C; Byrne, Christopher D

    2015-12-01

    Genetic variation in both patatin-like phospholipase domain-containing protein-3 (PNPLA3) (I148M) and the transmembrane 6 superfamily member 2 protein (TM6SF2) (E167K) influences severity of liver disease, and serum triglyceride concentrations in non-alcoholic fatty liver disease (NAFLD), but whether either genotype influences the responses to treatments is uncertain. One hundred three patients with NAFLD were randomised to omega-3 fatty acids (DHA+EPA) or placebo for 15-18months in a double blind placebo controlled trial. Erythrocyte enrichment with DHA and EPA was measured by gas chromatography. PNPLA3 and TM6SF2 genotypes were measured by PCR technologies. Multivariable linear regression and analysis of covariance were undertaken to test the effect of genotypes on omega-3 fatty acid enrichment, end of study liver fat percentage and serum triglyceride concentrations. All models were adjusted for baseline measurements of each respective outcome. Fifty-five men and 40 women (Genotypes PNPLA3 I148M, 148I/I=41, 148I/M=43, 148M/M=11; TM6SF2 E167K 167E/E=78, 167E/K+167K/K=17 participants) (mean ± SD age, 51 ± 11 years) completed the trial. Adjusting for baseline measurement, measured covariates and confounders, PNPLA3 148M/M variant was independently associated with percentage of DHA enrichment (B coefficient -1.02 (95% CI -1.97, -0.07), p=0.036) but not percentage of EPA enrichment (B coefficient -0.31 (95% CI -1.38, 0.75), p=0.56). This genotype was also independently associated with end of study liver fat percentage (B coefficient 9.5 (95% CI 2.53, 16.39), p=0.008), but not end of study triglyceride concentration (B coefficient -0.11 (95% CI -0.64, 0.42), p=0.68). PNPLA3 148M/M variant influences the changes in liver fat and DHA tissue enrichment during the trial but not the change in serum triglyceride concentration. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  10. Serum levels of advanced glycation end-products (AGEs) and the decoy soluble receptor for AGEs (sRAGE) can identify non-alcoholic fatty liver disease in age-, sex- and BMI-matched normo-glycemic adults.

    PubMed

    Palma-Duran, Susana A; Kontogianni, Meropi D; Vlassopoulos, Antonis; Zhao, Shudong; Margariti, Aikaterini; Georgoulis, Michael; Papatheodoridis, George; Combet, Emilie

    2018-06-01

    Non-alcoholic fatty liver disease (NAFLD) is a serious health problem affecting ~25% of the global population. While NAFLD pathogenesis is still unclear, multiple NAFLD parameters, including reduced insulin sensitivity, impaired glucose metabolism and increased oxidative stress are hypothesised to foster the formation of advanced glycation end-products (AGEs). Given the link of AGEs with end organ damage, there is scope to examine the role of the AGE/RAGE axis activation in liver injury and NAFLD. Age, sex and body mass index matched normo-glycemic NAFLD adults (n = 58) and healthy controls (n = 58) were enrolled in the study. AGEs were analysed by liquid chromatography-mass spectrometry (CML, CEL), fluorescence (pentosidine, AGE fluorescence), colorimetry (fructosamine) and ELISA (sRAGE). Their association with liver function, inflammation, fibrosis and stage of NAFLD was examined. Early and advanced glycation end-products, except N ε -carboxymethyl-L-lysine (CML), were 10-30% higher, sRAGE levels 1.7-fold lower, and glycation/sRAGE ratios 4-fold higher in the NAFLD cases compared to controls. While AGEs presented weak to moderate correlations with indices of liver function and damage (AST/ALT, HOMA-IR, TNF-α and TGF-β1), including sRAGE to characterize the AGEs/sRAGE axis strengthened the associations observed. High glycation/sRAGE ratios were associated with 1.3 to 14-fold likelihood of lower AST/ALT ratios. The sum of AGEs/sRAGE ratios accurately distinguished between healthy controls and NAFLD patients (area under the curve of 0.85). Elevated AGEs/sRAGE (>7.8 mmol/pmol) was associated with a 12-fold likelihood of the presence of NAFLD. These findings strengthen the involvement of AGEs-RAGE axis in liver injury and the pathogenesis of NAFLD. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis?

    PubMed

    Targher, Giovanni; Rossini, Maurizio; Lonardo, Amedeo

    2016-02-01

    Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are associated with obesity, insulin resistance, metabolic syndrome, cardiovascular disease, cirrhosis, and liver tumors. On these grounds, we have hypothesized that NAFLD and PCOS occur more frequently than expected by chance alone. We have tested this hypothesis by reviewing the clinical and biological evidence that supports a significant association between NAFLD and PCOS. PubMed was extensively searched for articles published through March 2015 using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "PCOS." Several cross-sectional and case-control studies have consistently demonstrated that the prevalence of NAFLD is remarkably increased in young women with PCOS, independent of overweight/obesity and other coexisting metabolic syndrome features, and that these women are more likely to have the more severe forms of NAFLD (non-alcoholic steatohepatitis, advanced fibrosis, and cirrhosis). Accumulating evidence suggests that NAFLD, especially its necro-inflammatory form, may exacerbate hepatic and systemic insulin resistance and releases multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators that may play important roles in the pathophysiology of PCOS. These findings call for more active and systematic search for NAFLD among women with PCOS. Conversely, gastroenterologists/hepatologists need to be aware of the presence of PCOS among female patients with NAFLD and compatible clinical features. Finally, all these patients should undergo regular follow-up not only for liver-related complications but also for cardio-metabolic diseases.

  12. Numerical scoring for the Classic BILAG index.

    PubMed

    Cresswell, Lynne; Yee, Chee-Seng; Farewell, Vernon; Rahman, Anisur; Teh, Lee-Suan; Griffiths, Bridget; Bruce, Ian N; Ahmad, Yasmeen; Prabu, Athiveeraramapandian; Akil, Mohammed; McHugh, Neil; Toescu, Veronica; D'Cruz, David; Khamashta, Munther A; Maddison, Peter; Isenberg, David A; Gordon, Caroline

    2009-12-01

    To develop an additive numerical scoring scheme for the Classic BILAG index. SLE patients were recruited into this multi-centre cross-sectional study. At every assessment, data were collected on disease activity and therapy. Logistic regression was used to model an increase in therapy, as an indicator of active disease, by the Classic BILAG score in eight systems. As both indicate inactivity, scores of D and E were set to 0 and used as the baseline in the fitted model. The coefficients from the fitted model were used to determine the numerical values for Grades A, B and C. Different scoring schemes were then compared using receiver operating characteristic (ROC) curves. Validation analysis was performed using assessments from a single centre. There were 1510 assessments from 369 SLE patients. The currently used coding scheme (A = 9, B = 3, C = 1 and D/E = 0) did not fit the data well. The regression model suggested three possible numerical scoring schemes: (i) A = 11, B = 6, C = 1 and D/E = 0; (ii) A = 12, B = 6, C = 1 and D/E = 0; and (iii) A = 11, B = 7, C = 1 and D/E = 0. These schemes produced comparable ROC curves. Based on this, A = 12, B = 6, C = 1 and D/E = 0 seemed a reasonable and practical choice. The validation analysis suggested that although the A = 12, B = 6, C = 1 and D/E = 0 coding is still reasonable, a scheme with slightly less weighting for B, such as A = 12, B = 5, C = 1 and D/E = 0, may be more appropriate. A reasonable additive numerical scoring scheme based on treatment decision for the Classic BILAG index is A = 12, B = 5, C = 1, D = 0 and E = 0.

  13. Numerical scoring for the Classic BILAG index

    PubMed Central

    Cresswell, Lynne; Yee, Chee-Seng; Farewell, Vernon; Rahman, Anisur; Teh, Lee-Suan; Griffiths, Bridget; Bruce, Ian N.; Ahmad, Yasmeen; Prabu, Athiveeraramapandian; Akil, Mohammed; McHugh, Neil; Toescu, Veronica; D’Cruz, David; Khamashta, Munther A.; Maddison, Peter; Isenberg, David A.

    2009-01-01

    Objective. To develop an additive numerical scoring scheme for the Classic BILAG index. Methods. SLE patients were recruited into this multi-centre cross-sectional study. At every assessment, data were collected on disease activity and therapy. Logistic regression was used to model an increase in therapy, as an indicator of active disease, by the Classic BILAG score in eight systems. As both indicate inactivity, scores of D and E were set to 0 and used as the baseline in the fitted model. The coefficients from the fitted model were used to determine the numerical values for Grades A, B and C. Different scoring schemes were then compared using receiver operating characteristic (ROC) curves. Validation analysis was performed using assessments from a single centre. Results. There were 1510 assessments from 369 SLE patients. The currently used coding scheme (A = 9, B = 3, C = 1 and D/E = 0) did not fit the data well. The regression model suggested three possible numerical scoring schemes: (i) A = 11, B = 6, C = 1 and D/E = 0; (ii) A = 12, B = 6, C = 1 and D/E = 0; and (iii) A = 11, B = 7, C = 1 and D/E = 0. These schemes produced comparable ROC curves. Based on this, A = 12, B = 6, C = 1 and D/E = 0 seemed a reasonable and practical choice. The validation analysis suggested that although the A = 12, B = 6, C = 1 and D/E = 0 coding is still reasonable, a scheme with slightly less weighting for B, such as A = 12, B = 5, C = 1 and D/E = 0, may be more appropriate. Conclusions. A reasonable additive numerical scoring scheme based on treatment decision for the Classic BILAG index is A = 12, B = 5, C = 1, D = 0 and E = 0. PMID:19779027

  14. Correlation between severity of ultrasonographic nonalcoholic fatty liver disease and cardiometabolic risk among Filipino wellness patients

    PubMed Central

    Cuenza, Lucky R.; Razon, Tamara Louise J.; Dayrit, Juan Carlo

    2017-01-01

    Introduction: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition which is known to be related to factors that predispose to the development of coronary artery disease as well as development of metabolic syndrome. The study aimed to determine the association between ultrasound-based grading of hepatic steatosis with metabolic profile and estimated cardiovascular risk using the Framingham Risk Score (FRS). Methods: This was a cross-sectional study on 100 Filipino patients without established cardiovascular disease who underwent a general wellness health evaluation. Cases with NAFLD diagnosed on the basis of ultrasound grading were analyzed. Comparison of demographics and metabolic parameters between grades of hepatic steatosis was performed using Kruskal Wallis test. FRS was used to assess cardiovascular risk with Spearman rank test for correlation with the degree of NAFLD. Results: Mean age was 47 ± 9.6 years, with 70% males. Mean body mass index (BMI) was 28.7 ± 5.1. Most patients had grade I NAFLD (53%), 34% were grade II, and 13% were grade III. BMI (P =0.034), liver enzymes (alanine aminotransferase [ALT], P = 0.001; aspartate aminotransferase [AST], P = 0.00), triglycerides (P = 0.047), and fasting blood sugar [FBS] (P = 0.049) were associated with fatty liver grade. No association was noted with total cholesterol (P = 0.569), high density lipoprotein (HDL) (P = 0.220), and low density lipoprotein (LDL) (P = 0.792). Using the FRS 43% were stratified as low (<10% risk), 45% as intermediate (10%-20% risk) and 12% as high risk (>20% risk). Severity of fatty liver was directly correlated with the FRS (Spearman rank 0.741, P = 0.009). Conclusion: Ultrasound-based grading of the severity of NAFLD is associated with abnormalities in the metabolic profile of patients. The FRS is correlated with increasing severity of NAFLD based on ultrasound. These findings suggest that the presence of NAFLD may be a marker for the presence of increased cardiovascular

  15. The Zhongshan Score

    PubMed Central

    Zhou, Lin; Guo, Jianming; Wang, Hang; Wang, Guomin

    2015-01-01

    Abstract In the zero ischemia era of nephron-sparing surgery (NSS), a new anatomic classification system (ACS) is needed to adjust to these new surgical techniques. We devised a novel and simple ACS, and compared it with the RENAL and PADUA scores to predict the risk of NSS outcomes. We retrospectively evaluated 789 patients who underwent NSS with available imaging between January 2007 and July 2014. Demographic and clinical data were assessed. The Zhongshan (ZS) score consisted of three parameters. RENAL, PADUA, and ZS scores are divided into three groups, that is, high, moderate, and low scores. For operative time (OT), significant differences were seen between any two groups of ZS score and PADUA score (all P < 0.05). For ZS score, patients with moderate and high scores had longer warm ischemia time (WIT) and greater increase in SCr compared with low score (all P < 0.05). What is more, the differences between moderate and high scores classified by ZS score were borderline but trending toward significance in WIT (P = 0.064) and increase in SCr (P = 0.052). Interestingly, RENAL showed no significant difference between moderate and high complexity in OT, WIT, estimated blood loss, and increase in SCr. Compared with patients with a low score of ZS, those with a high or moderate score had 8.1-fold or 3.3-fold higher risk of surgical complications, respectively (all P < 0.05). As for RENAL score, patients with a high or moderate score had 5.7-fold or 1.9-fold higher risk of surgical complications, respectively (all P < 0.05). Patients with a high or moderate score of PADUA had 2.3-fold or 2.8-fold higher risk of surgical complications, respectively (all P < 0.05). In the ROC curve analysis, ZS score had the greatest AUC for surgical complications (AUC = 0.632) and the conversion to radical nephrectomy (AUC = 0.845) (all P < 0.05). In conclusion, the ability of ZS score to predict the surgical complexity and surgical

  16. Food components with antifibrotic activity and implications in prevention of liver disease.

    PubMed

    Bae, Minkyung; Park, Young-Ki; Lee, Ji-Young

    2018-05-01

    Increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in parallel with the obesity epidemic has been a major public health concern. NAFLD is the most common chronic liver disease in the United States, ranging from fatty liver to steatohepatitis, fibrosis and cirrhosis in the liver. In response to chronic liver injury, fibrogenesis in the liver occurs as a protective response; however, prolonged and dysregulated fibrogenesis can lead to liver fibrosis, which can further progress to cirrhosis and eventually hepatocellular carcinoma. Interplay of hepatocytes, macrophages and hepatic stellate cells (HSCs) in the hepatic inflammatory and oxidative milieu is critical for the development of NAFLD. In particular, HSCs play a major role in the production of extracellular matrix proteins. Studies have demonstrated that bioactive food components and natural products, including astaxanthin, curcumin, blueberry, silymarin, coffee, vitamin C, vitamin E, vitamin D, resveratrol, quercetin and epigallocatechin-3-gallate, have antifibrotic effects in the liver. This review summarizes current knowledge of the mechanistic insight into the antifibrotic actions of the aforementioned bioactive food components. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Effect of two different hypocaloric diets in transaminases and insulin resistance in nonalcoholic fatty liver disease and obese patients.

    PubMed

    de Luis, D A; Aller, R; Izaola, O; Gonzalez Sagrado, M; Conde, R

    2010-01-01

    The aim of our study was to examine the changes in hypertransaminasemia after weight reduction in obese patients with and without NAFLD and the relation with insulin resistance. A population of 162 obese patients was randomly allocated to two groups: a) diet I (low fat) and b) diet II (low carbohydrate), dieting along 3 months. Patients were classified as group I (n=112) when serum ALT activity was normal or group II (NAFLD, n=30) when serum ALT activity was (>or=43 UI/L). In control group with diet I, BMI, weight, fat mass, waist to hip ratio, waist circumference, systolic pressure, total cholesterol, LDL cholesterol, HOMA and insulin levels decreased. In NAFLD group with diet I improved the same parameters and glucose, triglycerides, ALT, AST, gamaglutamine transferase levels, too. In control group with diet II, BMI, weight, fat mass, waist to hip ratio, waist circumference, systolic pressure, total cholesterol, LDL cholesterol, HOMA and insulin levels decreased. In NAFLD group with diet II improved the same parameters and glucose, triglycerides, ALT and gamaglutamine transferase levels, without statistical changes in AST. We showed that weight reduction secondary to two hypocaloric diets was associated with improvement in hipertransaminasemia and insulin resistance in NAFLD patients.

  18. Reduction of obesity-associated white adipose tissue inflammation by rosiglitazone is associated with reduced non-alcoholic fatty liver disease in LDLr-deficient mice.

    PubMed

    Mulder, Petra; Morrison, Martine C; Verschuren, Lars; Liang, Wen; van Bockel, J Hajo; Kooistra, Teake; Wielinga, Peter Y; Kleemann, Robert

    2016-08-22

    Obesity is associated with chronic low-grade inflammation that drives the development of metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). We recently showed that white adipose tissue (WAT) constitutes an important source of inflammatory factors. Hence, interventions that attenuate WAT inflammation may reduce NAFLD development. Male LDLr-/- mice were fed a high-fat diet (HFD) for 9 weeks followed by 7 weeks of HFD with or without rosiglitazone. Effects on WAT inflammation and NAFLD development were analyzed using biochemical and (immuno)histochemical techniques, combined with gene expression analyses. Nine weeks of HFD feeding induced obesity and WAT inflammation, which progressed gradually until the end of the study. Rosiglitazone fully blocked progression of WAT inflammation and activated PPARγ significantly in WAT. Rosiglitazone intervention did not activate PPARγ in liver, but improved liver histology and counteracted the expression of genes associated with severe NAFLD in humans. Rosiglitazone reduced expression of pro-inflammatory factors in WAT (TNF-α, leptin) and increased expression of adiponectin, which was reflected in plasma. Furthermore, rosiglitazone lowered circulating levels of pro-inflammatory saturated fatty acids. Together, these observations provide a rationale for the observed indirect hepatoprotective effects and suggest that WAT represents a promising therapeutic target for the treatment of obesity-associated NAFLD.

  19. Increased soluble CD36 is linked to advanced steatosis in nonalcoholic fatty liver disease.

    PubMed

    García-Monzón, Carmelo; Lo Iacono, Oreste; Crespo, Javier; Romero-Gómez, Manuel; García-Samaniego, Javier; Fernández-Bermejo, Miguel; Domínguez-Díez, Agustín; Rodríguez de Cía, Javier; Sáez, Alicia; Porrero, José Luís; Vargas-Castrillón, Javier; Chávez-Jiménez, Enrique; Soto-Fernández, Susana; Díaz, Ainhoa; Gallego-Durán, Rocío; Madejón, Antonio; Miquilena-Colina, María Eugenia

    2014-01-01

    Soluble CD36 (sCD36) clusters with insulin resistance, but no evidence exists on its relationship with hepatic fat content. We determined sCD36 to assess its link to steatosis in nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) patients. Two hundred and twenty-seven NAFLD, eighty-seven CHC, and eighty-five patients with histologically normal liver (NL) were studied. Steatosis was graded by Kleiner's histological scoring system. Serum sCD36 and hepatic CD36 expression was assessed by immunoassay and immunohistochemistry, respectively. In NAFLD, serum sCD36 levels were significantly higher in simple steatosis than in NL (361.4 ± 286.4 vs. 173.9 ± 137.4 pg/mL, respectively; P < 0.001), but not in steatohepatitis (229.6 ± 202.5 pg/mL; P = 0.153). In CHC, serum sCD36 levels were similar regardless of the absence (428.7 ± 260.3 pg/mL) or presence of steatosis (387.2 ± 283.6 pg/mL; P = 0.173). A progressive increase in serum sCD36 values was found in NAFLD depending on the histological grade of steatosis (P < 0.001), but not in CHC (P = 0.151). Serum sCD36 concentrations were independently associated with advanced steatosis in NAFLD when adjusted by demographic and anthropometric features [odds ratio (OR), 1.001; 95% confidence interval (CI), 1.000 to 1.002; P = 0.021] and by metabolic variables (OR, 1.002; 95% CI, 1.000 to 1.003; P = 0.001). Interestingly, a significant correlation was observed between hepatic CD36 and serum sCD36 (ρ = 0.499, P < 0.001). Increased serum sCD36 is an independent factor associated with advanced steatosis in NAFLD. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  20. Systems view of adipogenesis via novel omics-driven and tissue-specific activity scoring of network functional modules

    NASA Astrophysics Data System (ADS)

    Nassiri, Isar; Lombardo, Rosario; Lauria, Mario; Morine, Melissa J.; Moyseos, Petros; Varma, Vijayalakshmi; Nolen, Greg T.; Knox, Bridgett; Sloper, Daniel; Kaput, Jim; Priami, Corrado

    2016-07-01

    The investigation of the complex processes involved in cellular differentiation must be based on unbiased, high throughput data processing methods to identify relevant biological pathways. A number of bioinformatics tools are available that can generate lists of pathways ranked by statistical significance (i.e. by p-value), while ideally it would be desirable to functionally score the pathways relative to each other or to other interacting parts of the system or process. We describe a new computational method (Network Activity Score Finder - NASFinder) to identify tissue-specific, omics-determined sub-networks and the connections with their upstream regulator receptors to obtain a systems view of the differentiation of human adipocytes. Adipogenesis of human SBGS pre-adipocyte cells in vitro was monitored with a transcriptomic data set comprising six time points (0, 6, 48, 96, 192, 384 hours). To elucidate the mechanisms of adipogenesis, NASFinder was used to perform time-point analysis by comparing each time point against the control (0 h) and time-lapse analysis by comparing each time point with the previous one. NASFinder identified the coordinated activity of seemingly unrelated processes between each comparison, providing the first systems view of adipogenesis in culture. NASFinder has been implemented into a web-based, freely available resource associated with novel, easy to read visualization of omics data sets and network modules.

  1. Feasibility of and agreement between MR imaging and spectroscopic estimation of hepatic proton density fat fraction in children with known or suspected nonalcoholic fatty liver disease.

    PubMed

    Achmad, Emil; Yokoo, Takeshi; Hamilton, Gavin; Heba, Elhamy R; Hooker, Jonathan C; Changchien, Christopher; Schroeder, Michael; Wolfson, Tanya; Gamst, Anthony; Schwimmer, Jeffrey B; Lavine, Joel E; Sirlin, Claude B; Middleton, Michael S

    2015-10-01

    To assess feasibility of and agreement between magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for estimating hepatic proton density fat fraction (PDFF) in children with known or suspected nonalcoholic fatty liver disease (NAFLD). Children were included in this study from two previous research studies in each of which three MRI and three MRS acquisitions were obtained. Sequence acceptability, and MRI- and MRS-estimated PDFF were evaluated. Agreement of MRI- with MRS-estimated hepatic PDFF was assessed by linear regression and Bland-Altman analysis. Age, sex, BMI-Z score, acquisition time, and artifact score effects on MRI- and MRS-estimated PDFF agreement were assessed by multiple linear regression. Eighty-six children (61 boys and 25 girls) were included in this study. Slope and intercept from regressing MRS-PDFF on MRI-PDFF were 0.969 and 1.591%, respectively, and the Bland-Altman bias and 95% limits of agreement were 1.17% ± 2.61%. MRI motion artifact score was higher in boys than girls (by 0.21, p = 0.021). Higher BMI-Z score was associated with lower agreement between MRS and MRI (p = 0.045). Hepatic PDFF estimation by both MRI and MRS is feasible, and MRI- and MRS-estimated PDFF agree closely in children with known or suspected NAFLD.

  2. Choline intake in a large cohort of patients with nonalcoholic fatty liver disease123

    PubMed Central

    Guerrerio, Anthony L; Colvin, Ryan M; Schwartz, Amy K; Molleston, Jean P; Murray, Karen F; Diehl, AnnaMae; Mohan, Parvathi; Schwimmer, Jeffrey B; Lavine, Joel E; Torbenson, Michael S

    2012-01-01

    Background: There is significant histologic and biochemical overlap between nonalcoholic fatty liver disease (NAFLD) and steatohepatitis associated with choline deficiency. Objective: We sought to determine whether subjects with biopsy-proven NAFLD and evidence of an inadequate intake of choline had more severe histologic features. Design: We performed a cross-sectional analysis of 664 subjects enrolled in the multicenter, prospective Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) with baseline data on diet composition (from a recall-based food-frequency questionnaire) within 6 mo of a liver biopsy. Food questionnaires were analyzed with proprietary software to estimate daily intakes of choline. Liver biopsies were centrally read, and consensus was scored with the NASH CRN–developed scoring system. Because choline needs vary by age, sex, and menopausal status, participants were segregated into corresponding categories (children 9–13 y old, males ≥14 y old, premenopausal women ≥19 y old, and postmenopausal women) on the basis of the Institute of Medicine's definition of adequate intake (AI) for choline. Deficient intake was defined as <50% AI. Results: Postmenopausal women with deficient choline intake had worse fibrosis (P = 0.002) once factors associated with NAFLD (age, race-ethnicity, obesity, elevated triglycerides, diabetes, alcohol use, and steroid use) were considered in multiple ordinal logistic regression models. Choline intake was not identified as a contributor to disease severity in children, men, or premenopausal women. Conclusion: Decreased choline intake is significantly associated with increased fibrosis in postmenopausal women with NAFLD. The Pioglitazone vs Vitamin E vs Placebo for Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis trial was registered at clinicaltrials.gov as NCT00063622, and the Treatment of Nonalcoholic Fatty Liver Disease in Children trial was registered at clinicaltrials.gov as NCT

  3. Choline intake in a large cohort of patients with nonalcoholic fatty liver disease.

    PubMed

    Guerrerio, Anthony L; Colvin, Ryan M; Schwartz, Amy K; Molleston, Jean P; Murray, Karen F; Diehl, AnnaMae; Mohan, Parvathi; Schwimmer, Jeffrey B; Lavine, Joel E; Torbenson, Michael S; Scheimann, Ann O

    2012-04-01

    There is significant histologic and biochemical overlap between nonalcoholic fatty liver disease (NAFLD) and steatohepatitis associated with choline deficiency. We sought to determine whether subjects with biopsy-proven NAFLD and evidence of an inadequate intake of choline had more severe histologic features. We performed a cross-sectional analysis of 664 subjects enrolled in the multicenter, prospective Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) with baseline data on diet composition (from a recall-based food-frequency questionnaire) within 6 mo of a liver biopsy. Food questionnaires were analyzed with proprietary software to estimate daily intakes of choline. Liver biopsies were centrally read, and consensus was scored with the NASH CRN-developed scoring system. Because choline needs vary by age, sex, and menopausal status, participants were segregated into corresponding categories (children 9-13 y old, males ≥14 y old, premenopausal women ≥19 y old, and postmenopausal women) on the basis of the Institute of Medicine's definition of adequate intake (AI) for choline. Deficient intake was defined as <50% AI. Postmenopausal women with deficient choline intake had worse fibrosis (P = 0.002) once factors associated with NAFLD (age, race-ethnicity, obesity, elevated triglycerides, diabetes, alcohol use, and steroid use) were considered in multiple ordinal logistic regression models. Choline intake was not identified as a contributor to disease severity in children, men, or premenopausal women. Decreased choline intake is significantly associated with increased fibrosis in postmenopausal women with NAFLD. The Pioglitazone vs Vitamin E vs Placebo for Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis trial was registered at clinicaltrials.gov as NCT00063622, and the Treatment of Nonalcoholic Fatty Liver Disease in Children trial was registered at clinicaltrials.gov as NCT00063635.

  4. Low testosterone and non-alcoholic fatty liver disease: Evidence for their independent association in men with chronic spinal cord injury.

    PubMed

    Barbonetti, Arcangelo; Caterina Vassallo, Maria Rosaria; Cotugno, Michele; Felzani, Giorgio; Francavilla, Sandro; Francavilla, Felice

    2016-07-01

    Non-alcoholic fatty liver disease (NAFLD) has been claimed as a liver phenotype of metabolic syndrome, which in turn is associated with male hypogonadism. We assessed whether an independent association between NAFLD and androgen deficiency could be revealed in men with chronic spinal cord injury (SCI), who exhibit a high prevalence of biochemical androgen deficiency and a combination of risk factors for metabolic syndrome. Fifty-five consecutive men with chronic SCI admitted to a rehabilitation program underwent clinical/biochemical evaluations and liver ultrasonography. NAFLD was diagnosed in 27 patients (49.1%). Men with NAFLD were older and exhibited significantly higher body mass index, Homeostatic model assessment of insulin resistance, triglycerides and gamma-glutamyl transpeptidase values, lower total and free testosterone levels and they were engaged in a significantly poorer weekly leisure time physical activity (LTPA). At the multiple logistic regression analysis, only total and free testosterone levels exhibited a significant independent association with NAFLD. The risk of having NAFLD increased indeed of 1% for each decrement of 1 ng/dL of total testosterone and of 3% for each decrement of 1 pg/mL of free testosterone, after adjustment for confounders. In men with total testosterone < 300 ng/dL (36.4%) the prevalence of NAFLD reached 85%: they had a risk of having NAFLD significantly higher (∼12-fold) than those with total testosterone ≥ 300 ng/dL, after adjustment for confounders. The evidence of an independent association between NAFLD and low testosterone is strongly reinforced by its demonstration in men with chronic SCI, in spite of the many confounders peculiar to this population.

  5. College Math Assessment: SAT Scores vs. College Math Placement Scores

    ERIC Educational Resources Information Center

    Foley-Peres, Kathleen; Poirier, Dawn

    2008-01-01

    Many colleges and university's use SAT math scores or math placement tests to place students in the appropriate math course. This study compares the use of math placement scores and SAT scores for 188 freshman students. The student's grades and faculty observations were analyzed to determine if the SAT scores and/or college math assessment scores…

  6. Pharmacophore-Based Similarity Scoring for DOCK

    PubMed Central

    2015-01-01

    Pharmacophore modeling incorporates geometric and chemical features of known inhibitors and/or targeted binding sites to rationally identify and design new drug leads. In this study, we have encoded a three-dimensional pharmacophore matching similarity (FMS) scoring function into the structure-based design program DOCK. Validation and characterization of the method are presented through pose reproduction, crossdocking, and enrichment studies. When used alone, FMS scoring dramatically improves pose reproduction success to 93.5% (∼20% increase) and reduces sampling failures to 3.7% (∼6% drop) compared to the standard energy score (SGE) across 1043 protein–ligand complexes. The combined FMS+SGE function further improves success to 98.3%. Crossdocking experiments using FMS and FMS+SGE scoring, for six diverse protein families, similarly showed improvements in success, provided proper pharmacophore references are employed. For enrichment, incorporating pharmacophores during sampling and scoring, in most cases, also yield improved outcomes when docking and rank-ordering libraries of known actives and decoys to 15 systems. Retrospective analyses of virtual screenings to three clinical drug targets (EGFR, IGF-1R, and HIVgp41) using X-ray structures of known inhibitors as pharmacophore references are also reported, including a customized FMS scoring protocol to bias on selected regions in the reference. Overall, the results and fundamental insights gained from this study should benefit the docking community in general, particularly researchers using the new FMS method to guide computational drug discovery with DOCK. PMID:25229837

  7. Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents.

    PubMed

    Mosca, Antonella; Nobili, Valerio; De Vito, Rita; Crudele, Annalisa; Scorletti, Eleonora; Villani, Alberto; Alisi, Anna; Byrne, Christopher D

    2017-05-01

    Recent research has suggested that dietary fructose intake may increase serum uric acid (UA) concentrations. Both UA concentration and fructose consumption maybe also increase in NAFLD. It is not known whether dietary fructose consumption and UA concentration are independently associated with non-alcoholic steatohepatitis (NASH). Our aim was to investigate the factors associated with NASH in children and adolescents with proven NAFLD, and to test whether UA concentrations and fructose consumption are independently associated with NASH. Obese children with NAFLD were studied (n=271). NASH was diagnosed by a NAFLD activity score ⩾5 and the fatty liver inhibition of progression (FLIP) algorithm. Fructose consumption (g/day) was assessed by food frequency questionnaire, and UA (mg/dl) was measured in serum. Binary logistic regression with adjustment for covariates and potential confounders was undertaken to test factors independently associated with NASH. NASH occurred in 37.6% of patients. Hyperuricaemia (UA ⩾5.9mg/dl) was present in 47% of patients with NASH compared with 29.7% of non-NASH patients (p=0.003). Both UA concentration (OR=2.488, 95% CI: 1.87-2.83, p=0.004) and fructose consumption (OR=1.612, 95% CI 1.25-1.86, p=0.001) were independently associated with NASH, after adjustment for multiple (and all) measured confounders. Fructose consumption was independently associated with hyperuricaemia (OR=2.021, 95% CI: 1.66-2.78, p=0.01). These data were confirmed using the FLIP algorithm. Both dietary fructose consumption and serum UA concentrations are independently associated with NASH. Fructose consumption was the only factor independently associated with serum UA concentration. Currently, it is not known whether dietary fructose consumption and uric acid (UA) concentration are linked with non-alcoholic steatohepatitis (NASH) in children and adolescents. Our aim was to test whether UA concentrations and fructose consumption are independently associated with

  8. A Diet Score Assessing Norwegian Adolescents’ Adherence to Dietary Recommendations—Development and Test-Retest Reproducibility of the Score

    PubMed Central

    Handeland, Katina; Kjellevold, Marian; Wik Markhus, Maria; Eide Graff, Ingvild; Frøyland, Livar; Lie, Øyvind; Skotheim, Siv; Stormark, Kjell Morten; Dahl, Lisbeth; Øyen, Jannike

    2016-01-01

    Assessment of adolescents’ dietary habits is challenging. Reliable instruments to monitor dietary trends are required to promote healthier behaviours in this group. The purpose of this cross-sectional study was to assess adolescents’ adherence to Norwegian dietary recommendations with a diet score and to report results from, and test-retest reliability of, the score. The diet score involved seven food groups and one physical activity indicator, and was applied to answers from a semi-quantitative food frequency questionnaire (FFQ) administered twice. Reproducibility of the score was assessed with Cohen’s Kappa (κ statistics) at an interval of three months. The setting was eight lower-secondary schools in Hordaland County, Norway, and subjects were adolescents (n = 472) aged 14–15 years and their caregivers. Results showed that the proportion of adolescents consistently classified by the diet score was 87.6% (κ = 0.465). For food groups, proportions ranged from 74.0% to 91.6% (κ = 0.249 to κ = 0.573). Less than 40% of the participants were found to adhere to recommendations for frequencies of eating fruits, vegetables, added sugar, and fish. Highest compliance to recommendations was seen for choosing water as beverage and limit the intake of red meat. The score was associated with parental socioeconomic status. The diet score was found to be reproducible at an acceptable level. Health promoting work targeting adolescents should emphasize to increase the intake of recommended foods to approach nutritional guidelines. PMID:27483312

  9. A Diet Score Assessing Norwegian Adolescents' Adherence to Dietary Recommendations-Development and Test-Retest Reproducibility of the Score.

    PubMed

    Handeland, Katina; Kjellevold, Marian; Wik Markhus, Maria; Eide Graff, Ingvild; Frøyland, Livar; Lie, Øyvind; Skotheim, Siv; Stormark, Kjell Morten; Dahl, Lisbeth; Øyen, Jannike

    2016-07-29

    Assessment of adolescents' dietary habits is challenging. Reliable instruments to monitor dietary trends are required to promote healthier behaviours in this group. The purpose of this cross-sectional study was to assess adolescents' adherence to Norwegian dietary recommendations with a diet score and to report results from, and test-retest reliability of, the score. The diet score involved seven food groups and one physical activity indicator, and was applied to answers from a semi-quantitative food frequency questionnaire (FFQ) administered twice. Reproducibility of the score was assessed with Cohen's Kappa (κ statistics) at an interval of three months. The setting was eight lower-secondary schools in Hordaland County, Norway, and subjects were adolescents (n = 472) aged 14-15 years and their caregivers. Results showed that the proportion of adolescents consistently classified by the diet score was 87.6% (κ = 0.465). For food groups, proportions ranged from 74.0% to 91.6% (κ = 0.249 to κ = 0.573). Less than 40% of the participants were found to adhere to recommendations for frequencies of eating fruits, vegetables, added sugar, and fish. Highest compliance to recommendations was seen for choosing water as beverage and limit the intake of red meat. The score was associated with parental socioeconomic status. The diet score was found to be reproducible at an acceptable level. Health promoting work targeting adolescents should emphasize to increase the intake of recommended foods to approach nutritional guidelines.

  10. Translation and validation of the new version of the Knee Society Score - The 2011 KS Score - into Brazilian Portuguese.

    PubMed

    Silva, Adriana Lucia Pastore E; Croci, Alberto Tesconi; Gobbi, Riccardo Gomes; Hinckel, Betina Bremer; Pecora, José Ricardo; Demange, Marco Kawamura

    2017-01-01

    Translation, cultural adaptation, and validation of the new version of the Knee Society Score - The 2011 KS Score - into Brazilian Portuguese and verification of its measurement properties, reproducibility, and validity. In 2012, the new version of the Knee Society Score was developed and validated. This scale comprises four separate subscales: (a) objective knee score (seven items: 100 points); (b) patient satisfaction score (five items: 40 points); (c) patient expectations score (three items: 15 points); and (d) functional activity score (19 items: 100 points). A total of 90 patients aged 55-85 years were evaluated in a clinical cross-sectional study. The pre-operative translated version was applied to patients with TKA referral, and the post-operative translated version was applied to patients who underwent TKA. Each patient answered the same questionnaire twice and was evaluated by two experts in orthopedic knee surgery. Evaluations were performed pre-operatively and three, six, or 12 months post-operatively. The reliability of the questionnaire was evaluated using the intraclass correlation coefficient (ICC) between the two applications. Internal consistency was evaluated using Cronbach's alpha. The ICC found no difference between the means of the pre-operative, three-month, and six-month post-operative evaluations between sub-scale items. The Brazilian Portuguese version of The 2011 KS Score is a valid and reliable instrument for objective and subjective evaluation of the functionality of Brazilian patients who undergo TKA and revision TKA.

  11. The BRICS (Bronchiectasis Radiologically Indexed CT Score): A Multicenter Study Score for Use in Idiopathic and Postinfective Bronchiectasis.

    PubMed

    Bedi, Pallavi; Chalmers, James D; Goeminne, Pieter C; Mai, Cindy; Saravanamuthu, Pira; Velu, Prasad Palani; Cartlidge, Manjit K; Loebinger, Michael R; Jacob, Joe; Kamal, Faisal; Schembri, Nicola; Aliberti, Stefano; Hill, Uta; Harrison, Mike; Johnson, Christopher; Screaton, Nicholas; Haworth, Charles; Polverino, Eva; Rosales, Edmundo; Torres, Antoni; Benegas, Michael N; Rossi, Adriano G; Patel, Dilip; Hill, Adam T

    2018-05-01

    The goal of this study was to develop a simplified radiological score that could assess clinical disease severity in bronchiectasis. The Bronchiectasis Radiologically Indexed CT Score (BRICS) was devised based on a multivariable analysis of the Bhalla score and its ability in predicting clinical parameters of severity. The score was then externally validated in six centers in 302 patients. A total of 184 high-resolution CT scans were scored for the validation cohort. In a multiple logistic regression model, disease severity markers significantly associated with the Bhalla score were percent predicted FEV 1 , sputum purulence, and exacerbations requiring hospital admission. Components of the Bhalla score that were significantly associated with the disease severity markers were bronchial dilatation and number of bronchopulmonary segments with emphysema. The BRICS was developed with these two parameters. The receiver operating-characteristic curve values for BRICS in the derivation cohort were 0.79 for percent predicted FEV 1 , 0.71 for sputum purulence, and 0.75 for hospital admissions per year; these values were 0.81, 0.70, and 0.70, respectively, in the validation cohort. Sputum free neutrophil elastase activity was significantly elevated in the group with emphysema on CT imaging. A simplified CT scoring system can be used as an adjunct to clinical parameters to predict disease severity in patients with idiopathic and postinfective bronchiectasis. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  12. How much structuring is beneficial with regard to examination scores? A prospective study of three forms of active learning.

    PubMed

    Reinhardt, Claus H; Rosen, Evelyne N

    2012-09-01

    Many studies have demonstrated a superiority of active learning forms compared with traditional lecture. However, there is still debate as to what degree structuring is necessary with regard to high exam outcomes. Seventy-five students from a premedical school were randomly attributed to an active lecture group, a cooperative group, or a collaborative learning group. The active lecture group received lectures with questions to resolve at the end of the lecture. At the same time, the cooperative group and the collaborative group had to work on a problem and prepare presentations for their answers. The collaborative group worked in a mostly self-directed manner; the cooperative group had to follow a time schedule. For the additional work of preparing the poster presentation, the collaborative and cooperative groups were allowed 50% more working time. In part 1, all groups worked on the citric acid cycle, and in part 2, all groups worked on molecular genetics. Collaborative groups had to work on tasks and prepare presentations for their answers. At the end of each part, all three groups were subjected to the same exam. Additionally, in the collaborative and cooperative groups, the presentations were marked. All evaluations were performed by two independent examiners. Exam results of the active lecture groups were highest. Results of the cooperative group were nonsignificantly lower than the active lecture group and significantly higher than the collaborative group. The presentation quality was nonsignificantly higher in the collaborative group compared with the cooperative group. This study shows that active lecturing produced the highest exam results, which significantly differed from collaborative learning results. The additional elaboration in the cooperative and collaborative learning setting yielded the high presentation quality but apparently could not contribute further to exam scores. Cooperative learning seems to be a good compromise if high exam and

  13. Scoring Dawg Core Breakoff and Retention Mechanism

    NASA Technical Reports Server (NTRS)

    Badescu, Mircea; Sherrit, Stewart; Bar-Cohen, Yoseph; Bao, Xiaoqi; Backes, Paul G.

    2011-01-01

    This novel core break-off and retention mechanism consists of a scoring dawg controlled by a set of two tubes (a drill tube and an inner tube). The drill tube and the inner tube have longitudinal concentric holes. The solution can be implemented in an eccentric tube configuration as well where the tubes have eccentric longitudinal holes. The inner tube presents at the bottom two control surfaces for controlling the orientation of the scoring dawg. The drill tube presents a sunk-in profile on the inside of the wall for housing the scoring dawg. The inner tube rotation relative to the drill tube actively controls the orientation of the scoring dawg and hence its penetration and retrieval from the core. The scoring dawg presents a shaft, two axially spaced arms, and a tooth. The two arms slide on the control surfaces of the inner tube. The tooth, when rotated, can penetrate or be extracted from the core. During drilling, the two tubes move together maintaining the scoring dawg completely outside the core. After the desired drilling depth has been reached the inner tube is rotated relative to the drill tube such that the tooth of the scoring dawg moves toward the central axis. By rotating the drill tube, the scoring dawg can score the core and so reduce its cross sectional area. The scoring dawg can also act as a stress concentrator for breaking the core in torsion or tension. After breaking the core, the scoring dawg can act as a core retention mechanism. For scoring, it requires the core to be attached to the rock. If the core is broken, the dawg can be used as a retention mechanism. The scoring dawg requires a hard-tip insert like tungsten carbide for scoring hard rocks. The relative rotation of the two tubes can be controlled manually or by an additional actuator. In the implemented design solution the bit rotation for scoring was in the same direction as the drilling. The device was tested for limestone cores and basalt cores. The torque required for breaking the

  14. Automated Essay Scoring versus Human Scoring: A Comparative Study

    ERIC Educational Resources Information Center

    Wang, Jinhao; Brown, Michelle Stallone

    2007-01-01

    The current research was conducted to investigate the validity of automated essay scoring (AES) by comparing group mean scores assigned by an AES tool, IntelliMetric [TM] and human raters. Data collection included administering the Texas version of the WriterPlacer "Plus" test and obtaining scores assigned by IntelliMetric [TM] and by…

  15. Carbon monoxide protects against hepatic steatosis in mice by inducing sestrin-2 via the PERK-eIF2α-ATF4 pathway.

    PubMed

    Kim, Hyo Jeong; Joe, Yeonsoo; Kim, Seul-Ki; Park, Se-Ung; Park, Jeongmin; Chen, Yingqing; Kim, Jin; Ryu, Jinhyun; Cho, Gyeong Jae; Surh, Young-Joon; Ryter, Stefan W; Kim, Uh-Hyun; Chung, Hun-Taeg

    2017-09-01

    Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has emerged as one of the most common causes of chronic liver disease in developed countries over the last decade. NAFLD comprises a spectrum of pathological hepatic changes, including steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Autophagy, a homeostatic process for protein and organelle turnover, is decreased in the liver during the development of NAFLD. Previously, we have shown that carbon monoxide (CO), a reaction product of heme oxygenase (HO) activity, can confer protection in NAFLD, though the molecular mechanisms remain unclear. We therefore investigated the mechanisms underlying the protective effect of CO on methionine/choline-deficient (MCD) diet-induced hepatic steatosis. We found that CO induced sestrin-2 (SESN2) expression through enhanced mitochondrial ROS production and protected against MCD-induced NAFLD progression through activation of autophagy. SESN2 expression was increased by CO or CO-releasing molecule (CORM2), in a manner dependent on signaling through the protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor-2 alpha (eIF2α)/ activating transcription factor-4 (ATF4)-dependent pathway. CO-induced SESN2 upregulation in hepatocytes contributed to autophagy induction through activation of 5'-AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin (mTOR) complex I (mTORC1). Furthermore, we demonstrate that CO significantly induced the expression of SESN2 and enhanced autophagy in the livers of MCD-fed mice or in MCD-media treated hepatocytes. Conversely, knockdown of SESN2 abrogated autophagy activation and mTOR inhibition in response to CO. We conclude that CO ameliorates hepatic steatosis through the autophagy pathway induced by SESN2 upregulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. The role of the angiotensin II type I receptor blocker telmisartan in the treatment of non-alcoholic fatty liver disease: a brief review.

    PubMed

    Borém, Luciana M A; Neto, João F R; Brandi, Igor V; Lelis, Deborah F; Santos, Sergio H S

    2018-04-10

    Non-alcoholic fatty liver disease (NAFLD) is currently considered an important component of metabolic syndrome (MetS). The spectrum of NAFLD includes conditions that range from simple hepatic steatosis to non-alcoholic steatohepatitis. NAFLD is correlated with liver-related death and is predicted to be the most frequent indication for liver transplantation by 2030. Insulin resistance is directly correlated to the central mechanisms of hepatic steatosis in NAFLD patients, which is strongly correlated to the imbalance of the renin-angiotensin system, that is involved in lipid and glucose metabolism. Among the emerging treatment approaches for NAFLD is the anti-hypertensive agent telmisartan, which has positive effects on liver, lipid, and glucose metabolism, especially through its action on the renin-angiotensin system, by blocking the ACE/AngII/AT1 axis and increasing ACE2/Ang(1-7)/Mas axis activation. However, treatment with this drug is only recommended for patients with an established indication for anti-hypertensive therapy. Thus, there is an increased need for large randomized controlled trials with the aim of elucidating the effects of telmisartan on liver disease, especially NAFLD. From this perspective, the present review aims to provide a brief examination of the pathogenesis of NAFLD/NASH and the role of telmisartan on preventing liver disorders and thus to improve the discussion on potential therapies.

  17. Association between continuous positive airway pressure and serum aminotransferases in patients with obstructive sleep apnea.

    PubMed

    Chen, Li-Da; Zhang, Liang-Ji; Lin, Xue-Jun; Qi, Jia-Chao; Li, Hao; Wu, Zhi; Xu, Qiao-Zhen; Huang, Ya-Ping; Lin, Li

    2018-02-01

    Obstructive sleep apnea (OSA) has been suggested to be a potential contributing factor for nonalcoholic fatty liver disease (NAFLD). Studies on the association between continuous positive airway pressure (CPAP) and NAFLD in OSA patients are limited and controversial. The aim of this study was to assess the relationship between OSA and NAFLD and the effect of CPAP therapy on serum aminotransferase levels in OSA patients. A total of 160 consecutive patients who underwent standard polysomnography were enrolled. Blood samples were obtained in the morning after sleep for biological profile measurements. Non-invasive ultrasound techniques were used to assess liver steatosis and fibrosis. Within the OSA group, serum aminotransferases were detected before and after CPAP treatment. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase, and liver steatosis score increased significantly with an increase in OSA severity. Stepwise multiple regression with liver steatosis score, ALT, AST as dependent variable, respectively, apnea-hypopnea index (β = 0.447, p = 0.020; β = 0.266, p = 0.001; β = 0.351, p = 0.020, respectively) significantly predicted the liver steatosis score, ALT, AST after adjustment for confounders. After 3 months of CPAP treatment, there was a significant decrease in both ALT (54.20 ± 24.34 vs. 46.52 ± 24.95, p = 0.000) and AST (31.82 ± 8.91 vs. 29.00 ± 8.34, p = 0.039). OSA severity was independently associated with liver steatosis and elevation of serum aminotransferases. 3 months of CPAP therapy were associated with a statistically significant improvement on liver injury in OSA patients.

  18. Resveratrol supplement inhibited the NF-κB inflammation pathway through activating AMPKα-SIRT1 pathway in mice with fatty liver.

    PubMed

    Tian, Yueli; Ma, Jingting; Wang, Wudong; Zhang, Lingjuan; Xu, Jia; Wang, Kai; Li, Dongfu

    2016-11-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by high levels of nonesterified fatty acids (NEFA), inflammation, and hepatic steatosis. Inflammation plays a crucial role in the development of fatty liver. Resveratrol (RSV) supplement could improve inflammatory response and hepatic steatosis, whereas the underlying mechanism was not well understood. In this study, mice fed with high-fat diet (HFD) exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-α, IL-6, and IL-1β. Hepatic NF-κB inflammatory pathway was over-induced in HFD mice. In vitro, NEFA treatment further increased NF-κB pathway activation in mice hepatocytes, which then promoted the synthesis of inflammatory cytokines. Interestingly, RSV treatment significantly inhibited overactivation of NF-κB pathway and improved hepatic steatosis. Furthermore, RSV further increased the AMP-activated protein kinaseα (AMPKα) phosphorylation and sirtuin1 (SIRT1) protein levels to inhibit overactivation of NF-κB pathway induced by HFD or high levels of NEFA. AMPKα or SIRT1 inhibition significantly decreased the improvement effect of RSV on the NF-κB pathway induced by high levels of NEFA. Taken together, these findings indicate that RSV supplement decreases the inflammatory level and improves hepatic steatosis through activating AMPKα-SIRT1 pathway. Therefore, these data suggested an important clinical application of RSV in preventing NAFLD in humans.

  19. A CONSORT-Compliant, Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Purified Anthocyanin in Patients With Nonalcoholic Fatty Liver Disease

    PubMed Central

    Zhang, Pei-Wen; Chen, Feng-Xia; Li, Di; Ling, Wen-Hua; Guo, Hong-Hui

    2015-01-01

    Abstract Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that can progress to cirrhosis and liver failure. Anthocyanin, a member of the flavonoid family, has been shown to ameliorate NAFLD-associated pathologies in rodents. The aim of this CONSORT-compliant pilot study is to evaluate the effects of anthocyanin supplementation on insulin resistance and liver injury biomarkers in patients with NAFLD. A total of 74 subjects with NAFLD were divided into 2 groups in this double-blind, randomized study. Patients received either purified anthocyanin (320 mg/d) derived from bilberry and black currant or placebo for 12 weeks. Diet, physical activity, anthropometric parameters, glucose tolerance, and a set of biomarkers related to NAFLD were evaluated before and after intervention. No significant differences were observed in nutrient intake, physical activity, anthropometric parameters, or plasma lipid profile between patients receiving anthocyanin or placebo. Compared to controls, the anthocyanin group exhibited significant decreases (P < 0.05, all comparisons) in plasma alanine aminotransferase (−19.1% vs 3.1%), cytokeratin-18 M30 fragment (−8.8% vs 5.6%) and myeloperoxidase (−75.0% vs −44.8%). Significant decreases from baseline in fasting blood glucose and homeostasis model assessment for insulin resistance were observed in the anthocyanin group; however, these differences were not significant relative to placebo controls. In addition, the oral glucose tolerance test indicated that anthocyanin supplementation significantly decreased the 2-hour loading glucose level compared to control (−18.7% vs −3.8%, P = 0.02). A 12-week supplement of purified anthocyanin improved insulin resistance, indicators of liver injury, and clinical evolution in NAFLD patients. Further studies are warranted to determine the clinical applications of anthocyanin in NAFLD. This trial was registered at clinicaltrials.gov as NCT01940263. PMID:25997043

  20. Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation.

    PubMed

    Liu, Chang; Rajapakse, Angana G; Riedo, Erwin; Fellay, Benoit; Bernhard, Marie-Claire; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

    2016-02-05

    Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II(-/-) mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-α and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II(-/-) mice liver. Moreover, release of TNF-α and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II(-/-) mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II(-/-)-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-α and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-α and IL-6 in obesity.

  1. Searching for discrimination rules in protease proteolytic cleavage activity using genetic programming with a min-max scoring function.

    PubMed

    Yang, Zheng Rong; Thomson, Rebecca; Hodgman, T Charles; Dry, Jonathan; Doyle, Austin K; Narayanan, Ajit; Wu, XiKun

    2003-11-01

    This paper presents an algorithm which is able to extract discriminant rules from oligopeptides for protease proteolytic cleavage activity prediction. The algorithm is developed using genetic programming. Three important components in the algorithm are a min-max scoring function, the reverse Polish notation (RPN) and the use of minimum description length. The min-max scoring function is developed using amino acid similarity matrices for measuring the similarity between an oligopeptide and a rule, which is a complex algebraic equation of amino acids rather than a simple pattern sequence. The Fisher ratio is then calculated on the scoring values using the class label associated with the oligopeptides. The discriminant ability of each rule can therefore be evaluated. The use of RPN makes the evolutionary operations simpler and therefore reduces the computational cost. To prevent overfitting, the concept of minimum description length is used to penalize over-complicated rules. A fitness function is therefore composed of the Fisher ratio and the use of minimum description length for an efficient evolutionary process. In the application to four protease datasets (Trypsin, Factor Xa, Hepatitis C Virus and HIV protease cleavage site prediction), our algorithm is superior to C5, a conventional method for deriving decision trees.

  2. Definition of improvement in juvenile idiopathic arthritis using the juvenile arthritis disease activity score.

    PubMed

    Horneff, Gerd; Becker, Ingrid

    2014-07-01

    The aim of this study was to define improvement thresholds for the Juvenile Arthritis Disease Activity Score (JADAS). Physicians' and parents' judgements on treatment efficacy, the ACR paediatric response measure (PedACR) and JADAS were extracted from BIKER. Patients were categorized by baseline classes in the 10-joint JADAS (JADAS10) as low (5 to <15), moderate (15 to <25) and high (25 to ≤40). Cut-offs for defining improvement following treatment with biologics or MTX were chosen by calculating the interquartile ranges (IQRs) of the judgement groups and considering the accuracy, sensitivity and specificity of the resulting model. Differences in the change of JADAS10 by JIA category were also analysed by analysis of variance (ANOVA). Sensitivity, specificity and accuracy were calculated. A total of 1315 treatment courses were analysed. The ANOVA of the JIA categories showed no significant differences of the mean JADAS10 in all baseline classes and IQRs also showed good overall limits. Therefore all JIA categories were combined for a collective cut-off. Analysis by baseline class revealed clear cut-off points. Improvement could be defined by the minimal decrease in the JADAS10 in baseline class low by 4 (41%), moderate by 10 (53%) and high by 17 (57%). The model shows values for accuracy from 75.6 to 85.5% and comparable values for sensitivity and specificity. Improvement after 3 months can be defined efficiently by the decrease of the JADAS10, depending on the baseline JADAS10 score, which specifies low, moderate or high disease activity. Our model demonstrates clear cut-off values. The JADAS10 may be used in addition to ACR criteria in clinical trials. Also, since the JADAS10 can easily be calculated at each patient visit, it also can be used for clinical decisions. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Associations of prepartum body condition score with occurrence of clinical endometritis and resumption of postpartum ovarian activity in dairy cattle.

    PubMed

    Kadivar, Ali; Ahmadi, Mohammad Rahim; Vatankhah, Mahmood

    2014-01-01

    This study was performed to investigate the effect of periparturient body condition score on the occurrence of clinical endometritis and postpartum resumption of ovarian activity in dairy cows. Eighty-seven lactating Holstein cows, fed with a total mixed ration diet, were included into the study. Body condition scoring (using a 5-point scale with quarter-point divisions) was performed by the same investigator using the visual technique every 2 weeks, from 2 weeks before until 6 weeks after calving. Palpation of the reproductive tract and ultrasonographic assessment of ovaries for detection of corpus luteum using a rectal linear probe was also performed at 2, 4, and 6 weeks after calving. Cows with clinical endometritis had significantly lower body condition score (BCS) than normal cows at all weeks pre- and postcalving, and cows that did not ovulate until 45 days after calving had a significantly lower BCS pre- and postpartum. Cows that did not ovulate until 45 days after calving also lost more BCS from 2 weeks before to 4 weeks after calving. Besides, first ovulation after calving take occurred later in cows with clinical endometritis compared to normal cows (P < 0.05). In conclusion, low BCS is a risk factor for postpartum endometritis and delayed cyclicity in dairy cows. BCS loss from dry-off to early lactation and occurrence of clinical endometritis can significantly affect postpartum ovarian activity.

  4. Exploring a Source of Uneven Score Equity across the Test Score Range

    ERIC Educational Resources Information Center

    Huggins-Manley, Anne Corinne; Qiu, Yuxi; Penfield, Randall D.

    2018-01-01

    Score equity assessment (SEA) refers to an examination of population invariance of equating across two or more subpopulations of test examinees. Previous SEA studies have shown that score equity may be present for examinees scoring at particular test score ranges but absent for examinees scoring at other score ranges. No studies to date have…

  5. Performance-oriented mobility assessment (POMA) balance score indicates need for assistive device.

    PubMed

    Mitchell, Kathryn D; Newton, Roberta A

    2006-06-01

    To determine (1) if older adults using an assistive device (AD) score lower on the Performance-Oriented Mobility Assessment (POMA) balance subscale (B-subscale) than individuals not using an AD; and (2) if a cut-score of 12 would indicate the need to use an AD. Elderly persons (n = 82, mean age = 82.1 years) were surveyed about AD use, health status, activity level and fall history. A one-time assessment of balance was conducted using the B-subscale. The 'arising task' was repeated to evaluate performance on the sit-to-stand task without using hands. A significant difference in B-subscale scores was observed between the two groups (AD; no AD), (P < 0.001). AD use was associated with lower activity level and health status. A cut-score of 12 points indicated device use (P = 0.000). The repeated 'arising task' demonstrated that 76.8% performed the task without using hands for support. Older adults using an AD will score lower on the B-subscale and report lower activity level and health status. A score of less than 12 on the B-subscale is indicative of AD need. Older adults who use an AD and self-report a falls history will score lower on the B-subscale than individuals using an AD and no reported history of falls.

  6. Nonalcoholic fatty liver disease - A multisystem disease?

    PubMed Central

    Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470

  7. Knowing the Score

    ERIC Educational Resources Information Center

    Strouse, Lewis H.

    2009-01-01

    Before rehearsals begin, conductors need to thoroughly study the score. What elements go into a comprehensive score preparation? To learn music scores efficiently, having a detailed and systematic study method helps. The author has developed a score preparation guide that works for directors of bands, choruses, and orchestras, even when there's…

  8. Simplified Therapeutic Intervention Scoring System: the TISS-28 items--results from a multicenter study.

    PubMed

    Miranda, D R; de Rijk, A; Schaufeli, W

    1996-01-01

    To validate a simplified version of the Therapeutic Intervention Scoring System, the TISS-28, and to determine the association of TISS-28 with the time spent on scored and nonscored nursing activities. Prospective, multicenter study. Twenty-two adult medical, surgical, and general Dutch intensive care units (ICUs). A total of 903 patients consecutively admitted to the ICUs. TISS-28 was constructed from a random sample of 10,000 records of TISS-76 items. The respective weights were calculated using multivariable regression analysis through the origin; TISS-76 scores were used as predicted values. Cross validation was performed in another random sample of 10,000 records and the scores of TISS-76 were compared with those scores obtained with TISS-28 (r = .96, r2 = .93). Nursing activities in the ICU were inventoried and divided into six categories: a) activities in TISS-28; b) patient care activities not in TISS-28; c) indirect patient care (activities related to but not in direct contact with the patient, such as contact with family, maintaining supplies); d) organizational activities (e.g., meetings, trainee supervision, research); e) personal activities (for the nurse him/herself, such as taking a break, going to the bathroom); f) other. During a 1-month period, TISS-76 and TISS-28 scores were determined daily from the patient's records by independent raters. During a 1-wk period, all of the nurses on duty scored their activities using a method called "work sampling." The analysis of validation included 1,820 valid pairs of TISS-76 and TISS-28 records. The mean value of TISS-28 (28.8 +/- 11.1) was higher (p < .00) than that value of TISS-76 (24.2 +/- 10.2). TISS-28 explained 86% of the variation in TISS-76 (r = .93, r2 = .86). "Work sampling" generated 10,079 registrations of nursing activities, of which 5,530 could be matched with TISS-28 records. Samples were taken from medical (19.3%), surgical (19.1%), and general (61.6%) ICUs. Of these samples, 51

  9. “Always Look on the Bright Side of Life!” – Higher Hypomania Scores Are Associated with Higher Mental Toughness, Increased Physical Activity, and Lower Symptoms of Depression and Lower Sleep Complaints

    PubMed Central

    Jahangard, Leila; Rahmani, Anahita; Haghighi, Mohammad; Ahmadpanah, Mohammad; Sadeghi Bahmani, Dena; Soltanian, Ali R.; Shirzadi, Shahriar; Bajoghli, Hafez; Gerber, Markus; Holsboer-Trachsler, Edith; Brand, Serge

    2017-01-01

    Background: In the present study, we explored the associations between hypomania, symptoms of depression, sleep complaints, physical activity and mental toughness. The latter construct has gained interest for its association with a broad variety of favorable behavior in both clinical and non-clinical samples. Subjects and Methods: The non-clinical sample consisted of 206 young adults (M = 21.3 years; age range: 18–24 years; 57.3% males). They completed questionnaires covering hypomania, mental toughness, symptoms of depression, physical activity, and sleep quality. Results: Higher hypomania scores were associated with higher mental toughness, increased physical activity, lower symptoms of depression and lower sleep complaints. No gender differences were observed. Higher hypomania scores were predicted by higher scores of mental toughness subscales of control and challenge, and physical activity. Conclusion: The pattern of results suggests that among a non-clinical sample of young adults, self-rated hypomania scores were associated with higher scores on mental toughness and physical activity, along with lower depression and sleep complaints. The pattern of results further suggests that hypomania traits are associated with a broad range of favorable psychological, behavioral and sleep-related traits, at least among a non-clinical sample of young adults. PMID:29312026

  10. Pathology and biopsy assessment of non-alcoholic fatty liver disease.

    PubMed

    Straub, Beate Katharina; Schirmacher, Peter

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases in Western industrialized countries with dramatically rising incidence. The diagnosis of NAFLD requires the existence of steatosis in the absence of significant alcohol consumption. In cases of relevant inflammation pathogenetically linked to steatosis, it is termed non-alcoholic steatohepatitis (NASH). While pure steatosis represents a relatively harmless and rapidly reversible condition without a significant tendency to progression, NASH carries a significant morbidity and progression risk. Noninvasive methods neither reliably establish the diagnosis nor define the extent of disease in NASH, making histopathology the diagnostic gold standard. Since current therapeutic options in NASH are limited, indication for biopsy is made in the clinical context, predominantly in unclear clinical constellations, prior to invasive measures, for follow-up purposes and in the context of clinical studies. Histological hallmarks of NASH are steatosis, hepatocellular ballooning (with and without Mallory-Denk bodies), necroinflammation, and progressing disease a characteristic with perisinusoidal fibrosis. For semiquantitative assessment of necroinflammation (grading) and fibrosis (staging), a score has recently been implemented. Although histology does not reliably distinguish alcoholic steatohepatitis/alcoholic fatty liver disease from NASH/NAFLD, it may give valuable hints. NASH has a tendency for more steatosis, the so-called glycogenated nuclei, and less necroinflammatory activity. Future development of biopsy diagnosis will be coupled to the development of differential systemic therapeutic approaches. Especially in the context of clinical studies, detailed histological evaluation should be considered for the detection of predictive parameters. Copyright 2010 S. Karger AG, Basel.

  11. Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Disease: Prevalence and Risk Factors.

    PubMed

    Mariabeatrice, Principi; Andrea, Iannone; Giuseppe, Losurdo; Michela, Mangia; Endrit, Shahini; Francesca, Albano; Rizzi, Salvatore Fabio; La Fortezza, Rosa Federica; Rosa, Lovero; Antonella, Contaldo; Michele, Barone; Gioacchino, Leandro; Enzo, Ierardi; Alfredo, Di Leo

    2018-04-23

    Nonalcoholic fatty liver disease (NAFLD) is common in inflammatory bowel diseases (IBD). Herein, NAFLD prevalence and risk factors in a large IBD cohort were evaluated and compared to that of a non-IBD sample. Crohn's disease/ulcerative colitis outpatients referred to IBD service of our Gastroenterology Unit were enrolled. Subjects affected by functional and motor gastrointestinal disorders, in whom IBD was ruled out, referred to general outpatient service in the same area, were considered as nonIBD group. Exclusion criteria were based on previous diagnosis of nonNAFLD chronic liver diseases and secondary causes of fat liver overload. Characteristics of IBD and liver status were collected. Risk factors for metabolic syndrome were analyzed. Ultrasonographic presence and degree of steatosis were assessed. Data were examined by univariate and multivariate analyses. For this study 465 IBD and 189 non-IBD subjects were consecutively enrolled. NAFLD was found in 28.0% and 20.1% in IBD and non-IBD subjects, respectively (P = 0.04). IBD patients with NAFLD were younger than non-IBD ones. There was no significant difference in steatosis grade and association between NAFLD and IBD behavior, extension, activity, and drugs. In the IBD group, multivariate analysis demonstrated that NAFLD was independently associated to metabolic syndrome (OR=2.24, 95%CI 1.77-28.81), diabetes (OR=1.71, 95%CI 1.43-12.25), fasting blood glucose (OR=1.36, 95%CI 1.13-1.68), and abdominal circumference (OR=1.68, 95%CI 1.15-14.52). NAFLD is more common and occurs at a younger age in IBD than in nonIBD subjects. However, further investigation is required to ascertain possible NAFLD pathogenic IBD-related factors other than conventional/metabolic ones. 10.1093/ibd/izy051_video1izy051.video15774874877001.

  12. Estimation of a Preference-Based Summary Score for the Patient-Reported Outcomes Measurement Information System: The PROMIS®-Preference (PROPr) Scoring System.

    PubMed

    Dewitt, Barry; Feeny, David; Fischhoff, Baruch; Cella, David; Hays, Ron D; Hess, Rachel; Pilkonis, Paul A; Revicki, Dennis A; Roberts, Mark S; Tsevat, Joel; Yu, Lan; Hanmer, Janel

    2018-06-01

    Health-related quality of life (HRQL) preference-based scores are used to assess the health of populations and patients and for cost-effectiveness analyses. The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS ® ) consists of patient-reported outcome measures developed using item response theory. PROMIS is in need of a direct preference-based scoring system for assigning values to health states. To produce societal preference-based scores for 7 PROMIS domains: Cognitive Function-Abilities, Depression, Fatigue, Pain Interference, Physical Function, Sleep Disturbance, and Ability to Participate in Social Roles and Activities. Online survey of a US nationally representative sample ( n = 983). Preferences for PROMIS health states were elicited with the standard gamble to obtain both single-attribute scoring functions for each of the 7 PROMIS domains and a multiplicative multiattribute utility (scoring) function. The 7 single-attribute scoring functions were fit using isotonic regression with linear interpolation. The multiplicative multiattribute summary function estimates utilities for PROMIS multiattribute health states on a scale where 0 is the utility of being dead and 1 the utility of "full health." The lowest possible score is -0.022 (for a state viewed as worse than dead), and the highest possible score is 1. The online survey systematically excludes some subgroups, such as the visually impaired and illiterate. A generic societal preference-based scoring system is now available for all studies using these 7 PROMIS health domains.

  13. Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: assessment of non-invasive indices predicting hepatic steatosis and fibrosis.

    PubMed

    Polyzos, Stergios A; Goulis, Dimitrios G; Kountouras, Jannis; Mintziori, Gesthimani; Chatzis, Panagiotis; Papadakis, Efstathios; Katsikis, Ilias; Panidis, Dimitrios

    2014-01-01

    Insulin resistance contributes to the pathogenesis of both polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD). The main aim of the present study was the evaluation of non-invasive indices of hepatic steatosis and fibrosis in PCOS women with or without metabolic syndrome (MetS). In this cross-sectional study, three non-invasive indices for hepatic steatosis [NAFLD liver fat score, lipid accumulation product (LAP) and hepatic steatosis index (HIS)] and four for fibrosis [FIB-4, aspartate aminotransferase (AST)-to-Platelet Ratio Index (APRI), body mass index (BMI)-Age-Alanine aminotransferase (ALT)-Triglycerides (BAAT) and BMI AST/ALT Ratio Diabetes (BARD)] were calculated in 314 PCOS women (77 with, 237 without MetS) and 78 controls. All steatosis indices were significantly higher in the PCOS than the control group (NAFLD liver fat score: -0.139 ± 0.117 vs. -0.976 ± 0.159, p<0.001; LAP: 43.3 ± 1.9 vs. 34.7 ± 3.1, p=0.036; HIS: 44.6 ± 0.5 vs. 42.1 ± 0.8, p=0.016). FIB-4 and BAAT [fibrosis stage (F)2-4] were higher in the PCOS group (0.480 ± 0.020 vs. 0.400 ± 0.013, p<0.001; and 15.6% vs. 5.1%, respectively), whereas APRI and BARD were not. All steatosis indices were significantly higher in PCOS women with than without MetS (NAFLD liver fat score: 1.874 ± 0.258 vs. -0.793 ± 0.099, p<0.001; LAP: 76.8 ± 4.9 vs. 33.4 ± 1.4, p<0.001; and HIS: 49.8 ± 1 vs. 43 ± 0.5, p<0.001). Of the fibrosis indices, only BAAT (F2-4: 50.6% vs. 4.2%) was higher in PCOS women with MetS. Non-invasive indices of hepatic steatosis were significantly higher in PCOS, especially in the presence of MetS, whereas indices of hepatic fibrosis yielded controversial results. Further studies are warranted to evaluate the long-term outcomes of hepatic steatosis and fibrosis indices in PCOS women.

  14. Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

    PubMed Central

    Gentric, Géraldine; Maillet, Vanessa; Paradis, Valérie; Couton, Dominique; L’Hermitte, Antoine; Panasyuk, Ganna; Fromenty, Bernard; Celton-Morizur, Séverine; Desdouets, Chantal

    2015-01-01

    Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the parenchyma of fatty livers displayed alterations of the polyploidization process, including the presence of a large proportion of highly polyploid mononuclear cells, which are rarely observed in normal hepatic parenchyma. Biopsies from patients with nonalcoholic steatohepatitis (NASH) revealed the presence of alterations in hepatocyte ploidy compared with tissue from control individuals. Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of the cell cycle was inefficient. This alteration was associated with activation of a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1 complex. Furthermore, we determined that oxidative stress promotes the appearance of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed normal cell division and returned to a physiological state of polyploidy. Collectively, these findings indicate that oxidative stress promotes pathological polyploidization and suggest that this is an early event in NAFLD that may contribute to HCC development. PMID:25621497

  15. Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease.

    PubMed

    Gentric, Géraldine; Maillet, Vanessa; Paradis, Valérie; Couton, Dominique; L'Hermitte, Antoine; Panasyuk, Ganna; Fromenty, Bernard; Celton-Morizur, Séverine; Desdouets, Chantal

    2015-03-02

    Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the parenchyma of fatty livers displayed alterations of the polyploidization process, including the presence of a large proportion of highly polyploid mononuclear cells, which are rarely observed in normal hepatic parenchyma. Biopsies from patients with nonalcoholic steatohepatitis (NASH) revealed the presence of alterations in hepatocyte ploidy compared with tissue from control individuals. Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of the cell cycle was inefficient. This alteration was associated with activation of a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1 complex. Furthermore, we determined that oxidative stress promotes the appearance of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed normal cell division and returned to a physiological state of polyploidy. Collectively, these findings indicate that oxidative stress promotes pathological polyploidization and suggest that this is an early event in NAFLD that may contribute to HCC development.

  16. Vitex agnus-castus L. (Verbenaceae) Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats.

    PubMed

    Moreno, Franciele Neves; Campos-Shimada, Lilian Brites; da Costa, Silvio Claudio; Garcia, Rosângela Fernandes; Cecchini, Alessandra Lourenço; Natali, Maria Raquel Marçal; Vitoriano, Adriana de Souza; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

    2015-01-01

    Vitex agnus-castus (VAC) is a plant that has recently been used to treat the symptoms of menopause, by its actions on the central nervous system. However, little is known about its actions on disturbances in lipid metabolism and nonalcoholic fat liver disease (NAFLD), frequently associated with menopause. Ovariectomized (OVX) rats exhibit increased adiposity and NAFLD 13 weeks after ovary removal and were used as animal models of estrogen deficiency. The rats were treated with crude extract (CE) and a butanolic fraction of VAC (ButF) and displayed the beneficial effects of a reduction in the adiposity index and a complete reversion of NAFLD. NAFLD reversion was accompanied by a general improvement in the liver redox status. The activities of some antioxidant enzymes were restored and the mitochondrial hydrogen peroxide production was significantly reduced in animals treated with CE and the ButF. It can be concluded that the CE and ButF from Vitex agnus-castus were effective in preventing NAFLD and oxidative stress, which are frequent causes of abnormal liver functions in the postmenopausal period.

  17. Vitex agnus-castus L. (Verbenaceae) Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats

    PubMed Central

    Moreno, Franciele Neves; Campos-Shimada, Lilian Brites; da Costa, Silvio Claudio; Garcia, Rosângela Fernandes; Cecchini, Alessandra Lourenço; Natali, Maria Raquel Marçal; Vitoriano, Adriana de Souza; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

    2015-01-01

    Vitex agnus-castus (VAC) is a plant that has recently been used to treat the symptoms of menopause, by its actions on the central nervous system. However, little is known about its actions on disturbances in lipid metabolism and nonalcoholic fat liver disease (NAFLD), frequently associated with menopause. Ovariectomized (OVX) rats exhibit increased adiposity and NAFLD 13 weeks after ovary removal and were used as animal models of estrogen deficiency. The rats were treated with crude extract (CE) and a butanolic fraction of VAC (ButF) and displayed the beneficial effects of a reduction in the adiposity index and a complete reversion of NAFLD. NAFLD reversion was accompanied by a general improvement in the liver redox status. The activities of some antioxidant enzymes were restored and the mitochondrial hydrogen peroxide production was significantly reduced in animals treated with CE and the ButF. It can be concluded that the CE and ButF from Vitex agnus-castus were effective in preventing NAFLD and oxidative stress, which are frequent causes of abnormal liver functions in the postmenopausal period. PMID:25954315

  18. Nutritional Quality of Breakfast and Physical Activity Independently Predict the Literacy and Numeracy Scores of Children after Adjusting for Socioeconomic Status

    ERIC Educational Resources Information Center

    O'Dea, Jennifer A.; Mugridge, Anna C.

    2012-01-01

    Health-related behaviors [physical activity (PA), nutritional quality of breakfast and sleep]; personal variables (self-esteem, attitudes to PA and gender) and socioeconomic status (SES) (school SES and parental education), were examined in relation to literacy and numeracy scores of 824 grade 3-7 children. Participants completed a questionnaire,…

  19. Isocaloric Dietary Changes and Non-Alcoholic Fatty Liver Disease in High Cardiometabolic Risk Individuals.

    PubMed

    Della Pepa, Giuseppe; Vetrani, Claudia; Lombardi, Gianluca; Bozzetto, Lutgarda; Annuzzi, Giovanni; Rivellese, Angela Albarosa

    2017-09-26

    Non-alcoholic fatty liver disease (NAFLD) incorporates an extensive spectrum of histologic liver abnormalities, varying from simple triglyceride accumulation in hepatocytes non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), and it is the most frequent chronic liver disease in the industrialized world. Beyond liver related complications such as cirrhosis and hepatocellular carcinoma, NAFLD is also an emerging risk factor for type 2 diabetes and cardiovascular disease. Currently, lifestyle intervention including strategies to reduce body weight and to increase regular physical activity represents the mainstay of NAFLD management. Total caloric intake plays a very important role in both the development and the treatment of NAFLD; however, apart from the caloric restriction alone, modifying the quality of the diet and modulating either the macro- or micronutrient composition can also markedly affect the clinical evolution of NAFLD, offering a more realistic and feasible treatment alternative. The aim of the present review is to summarize currently available evidence from randomized controlled trials on the effects of different nutrients including carbohydrates, lipids, protein and other dietary components, in isocaloric conditions, on NAFLD in people at high cardiometabolic risk. We also describe the plausible mechanisms by which different dietary components could modulate liver fat content.

  20. Isocaloric Dietary Changes and Non-Alcoholic Fatty Liver Disease in High Cardiometabolic Risk Individuals

    PubMed Central

    Della Pepa, Giuseppe; Vetrani, Claudia; Lombardi, Gianluca; Bozzetto, Lutgarda; Annuzzi, Giovanni; Rivellese, Angela Albarosa

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) incorporates an extensive spectrum of histologic liver abnormalities, varying from simple triglyceride accumulation in hepatocytes non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), and it is the most frequent chronic liver disease in the industrialized world. Beyond liver related complications such as cirrhosis and hepatocellular carcinoma, NAFLD is also an emerging risk factor for type 2 diabetes and cardiovascular disease. Currently, lifestyle intervention including strategies to reduce body weight and to increase regular physical activity represents the mainstay of NAFLD management. Total caloric intake plays a very important role in both the development and the treatment of NAFLD; however, apart from the caloric restriction alone, modifying the quality of the diet and modulating either the macro- or micronutrient composition can also markedly affect the clinical evolution of NAFLD, offering a more realistic and feasible treatment alternative. The aim of the present review is to summarize currently available evidence from randomized controlled trials on the effects of different nutrients including carbohydrates, lipids, protein and other dietary components, in isocaloric conditions, on NAFLD in people at high cardiometabolic risk. We also describe the plausible mechanisms by which different dietary components could modulate liver fat content. PMID:28954437