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

OBJECTIVE Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. RESEARCH DESIGN AND METHODS This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. RESULTS The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m2, respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75–0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit

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

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.

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

Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m(2), respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with

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

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.

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.

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

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.

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

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

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.

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.

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

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.

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.

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

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, ...

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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

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

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.

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

[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.

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

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.

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

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

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.

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

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

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.

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

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.

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.

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

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.

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.

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.

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

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.

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

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.

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

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.

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.

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.

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.

Astronomia para/com crianças carentes em Limeira

NASA Astrophysics Data System (ADS)

Bretones, P. S.; Oliveira, V. C.

2003-08-01

Em 2001, o Instituto Superior de Ciências Aplicadas (ISCA Faculdades de Limeira) iniciou um projeto pelo qual o Observatório do Morro Azul empreendeu uma parceria com o Centro de Promoção Social Municipal (CEPROSOM), instituição mantida pela Prefeitura Municipal de Limeira para atender crianças e adolescentes carentes. O CEPROSOM contava com dois projetos: Projeto Centro de Convivência Infantil (CCI) e Programa Criança e Adolescente (PCA), que atendiam crianças e adolescentes em Centros Comunitários de diversas áreas da cidade. Esses projetos têm como prioridades estabelecer atividades prazerosas para as crianças no sentido de retirá-las das ruas. Assim sendo, as crianças passaram a ter mais um tipo de atividade - as visitas ao observatório. Este painel descreve as várias fases do projeto, que envolveu: reuniões de planejamento, curso de Astronomia para as orientadoras dos CCIs e PCAs, atividades relacionadas a visitas das crianças ao Observatório, proposta de construção de gnômons e relógios de Sol nos diversos Centros Comunitários de Limeira e divulgação do projeto na imprensa. O painel inclui discussões sobre a aprendizagem de crianças carentes, relatos que mostram a postura das orientadoras sobre a pertinência do ensino de Astronomia, relatos do monitor que fez o atendimento no Observatório e o que o número de crianças atendidas representou para as atividades da instituição desde o início de suas atividades e, em particular, em 2001. Os resultados são baseados na análise de relatos das orientadoras e do monitor do Observatório, registros de visitas e matérias da imprensa local. Conclui com uma avaliação do que tal projeto representou para as Instituições participantes. Para o Observatório, em particular, foi feita uma análise com relação às outras modalidades de atendimentos que envolvem alunos de escolas e público em geral. Também é abordada a questão do compromisso social do Observatório na educação do

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.

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.

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.

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.

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.

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

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

[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

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.

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

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.

Santé sexuelle et reproductive des adolescentes de Bobo Dioulasso, Burkina Faso: place de la communication parents-adolescentes pour la réduction des risques

PubMed Central

Some, Donmozoun Télesphore; Some, Der Adolphe; Hien, Hervé; Diallo, Ramata; Zingue, Dézémon; Diallo, Ibrahim; Diagbouga, Serge; Dao, Blami

2012-01-01

Introduction Les adolescentes sont très vulnérables face aux Infections Sexuellement Transmissibles (IST) et au VIH/SIDA. Notre étude a pour objectifs d’explorer la qualité de la communication entre les adolescentes et leurs parents sur les IST/VIH/SIDA et de recueillir leurs suggestions pour l’amélioration de cette communication. Méthodes L’étude était transversale qualitative sur 2 mois. La population de l’étude était composée par des adolescentes de 13 à 17 ans et leurs parents habitant la ville de Bobo Dioulasso. Vingt (20) adolescentes scolarisées ont été tirés au sort dans trois établissements secondaires et 20 autres non scolarisées choisies de façon accidentelle dans la ville. Les informations ont été collectées à l’aide de 8 focus groups. Les discussions ont été enregistrées sur cassettes, retranscrites en verbatim, et analysées à l’aide du logiciel QSR NVIVO 2.0. Résultats Les adolescentes et leurs parents communiquent très peu ou pas sur les questions des IST/VIH/SIDA; l’auto-information par les paires ou les médias est la première source d’information. Pour les parents, l’information existe et est accessible aux adolescentes alors que pour ces dernières, leurs connaissances de ces maladies sont parfois erronées. L’abstinence, la fidélité et le dépistage volontaire comme moyen de prévention sont très peu évoqués par les adolescentes de même que par leurs parents. Conclusion La communication parents-adolescentes est insuffisante voire absente dans certains milieux. Il est urgent de conduire des actions auprès des adolescentes et leurs parents pour mieux les informer sur les IST/VIH/SIDA et améliorer la communication sur ces maladies. PMID:22655099

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

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

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.

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.

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

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.

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.

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.

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

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

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.

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.

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

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.

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.

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 ¹³C-ketoisocaproate breath test (¹³C-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 ¹³C-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 ¹³C-KICA BT and expressed as cumulative % ¹³C-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 (R²= 41.5%; p<0.0001). In patients with NAFLD (compared to healthy subjects), there was a reduction in HMF assessed by the ¹³C-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.

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.

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.

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.

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.

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

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

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

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

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

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.

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.

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.

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.

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

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.

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.

ACTITUDES HACIA LA COMUNICACIÓN SEXUAL ENTRE PADRES/MADRES Y ADOLESCENTES EN PUERTO RICO*

PubMed Central

Fernández, Ana Michelle; McFarlane, Melvin Negrón; González, Ricardo; Díaz, Leslie; Betancourt-Díaz, Elba; Cintrón-Bou, Francheska; Varas-Díaz, Nelson; Villarruel, Antonia

2017-01-01

RESUMEN La comunicación sobre sexualidad entre padres/madres y adolescentes enfrenta dificultades particulares producto de factores socioculturales. Este estudio tuvo como objetivo documentar las actitudes de padres/madres y adolescentes hacia la comunicación sobre temas de sexualidad. Los resultados emanan de la medición inicial del Proyecto Cuídalos. Los datos de este estudio forman parte de un estudio amplio que evaluó un módulo interactivo basado en la web para mejorar comunicación sobre temas de salud entre padres/madres y adolescentes entre 13–17 años. En este artículo, reportamos datos basales que contestaron los/as participantes sobre comodidad al hablar sobre temas de salud sexual. La muestra, de los datos aquí expuestos, estuvo compuesta por 458 diadas de madres/padres y sus hijos/as adolescentes (n=916). Se realizó análisis de frecuencias y medidas de tendencia central con los datos obtenidos inicialmente. La edad promedio de los adolescentes fue de 15 años, de los que un 15% se encontraban activos sexualmente. Los/as adolescentes tienen mejor disposición que los/as padres/madres para hablar sobre sexualidad. Sin embargo, los/as padres/madres entienden que comparten suficiente información sobre temas relacionados a la sexualidad. Los/as padres/madres y adolescentes reportaron algún grado de dificultad e incomodidad al hablar sobre métodos específicos de prevención. Los resultados destacan la necesidad de incorporar a los/as padres/madres en intervenciones con adolescentes sobre temas de salud sexual. En Puerto Rico es necesario desarrollar programas dirigidos a minimizar las conductas sexuales de alto riesgo en jóvenes. PMID:28736599

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.

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.

ESTIGMA Y VIH/SIDA ENTRE PADRES/MADRES Y ADOLESCENTES PUERTORRIQUEÑOS/AS

PubMed Central

Pérez, Grace Rosado; Reyes, Glendalys Rivera; Villanueva, Victoria Larrieux; Torres, Gilliam J. Torres; Díaz, Elba Betancourt; Varas-Díaz, Nelson; Villaruel, Antonia

2016-01-01

La comunicación entre padres/madres y adolescentes sobre el tema de la sexualidad es importante para el desarrollo de la salud de personas jóvenes. Dicha comunicación puede verse negativamente impactada por actitudes estigmatizantes hacia el tema del VIH/SIDA. El objetivo de este estudio fue identificar actitudes estigmatizantes hacia el VIH/SIDA entre padres/madres y adolescentes puertorriqueños/as. Este esfuerzo es parte del Proyecto Cuídalos, dirigido a probar una intervención en formato electrónico que busca aumentar la comunicación sobre sexualidad y salud entre padres/madres y adolescentes mediante un diseño experimental con 458 diadas de padres/madres y adolescentes de 13 a 17 años. Para propósitos de este artículo reportamos estadísticas descriptivas sobre estigma hacia el VIH/SIDA con la información recopilada en la medición basal. Tanto adultos/as como adolescentes mostraron actitudes estigmatizantes hacia el VIH/SIDA. A la luz de los resultados es necesario continuar desarrollando intervenciones para la reducción de estigma en esta población. Los/as padres/madres pueden ser un recurso invaluable para reducir el estigma en los/as jóvenes, y prevenir conductas sexuales de riesgo e infecciones. PMID:27099649

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

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

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.

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.

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.

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.

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.

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

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.

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.

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

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

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.

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.

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.

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

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

[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.

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

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.

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.

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

In non-alcoholic fatty liver disease (NAFLD), lipid build-up and the resulting damage is known to occur more severely in pericentral cells. Due to the complexity of studying individual regions of the sinusoid, the causes of this zone specificity and its implications on treatment are largely ignored. In this study, a computational model of liver glucose and lipid metabolism is presented which treats the sinusoid as the repeating unit of the liver rather than the single hepatocyte. This allows for inclusion of zonated enzyme expression by splitting the sinusoid into periportal to pericentral compartments. By simulating insulin resistance (IR) and high intake diets leading to the development of steatosis in the model, we identify key differences between periportal and pericentral cells accounting for higher susceptibility to pericentral steatosis. Secondly, variation between individuals is seen in both susceptibility to steatosis and in its development across the sinusoid. Around 25% of obese individuals do not show excess liver fat, whilst 16% of lean individuals develop NAFLD. Furthermore, whilst pericentral cells tend to show higher lipid levels, variation is seen in the predominant location of steatosis from pericentral to pan-sinusoidal or azonal. Sensitivity analysis was used to identify the processes which have the largest effect on both total hepatic triglyceride levels and on the sinusoidal location of steatosis. As is seen in vivo, steatosis occurs when simulating IR in the model, predominantly due to increased uptake, along with an increase in de novo lipogenesis. Additionally, concentrations of glucose intermediates including glycerol-3-phosphate increased when simulating IR due to inhibited glycogen synthesis. Several differences between zones contributed to a higher susceptibility to steatosis in pericentral cells in the model simulations. Firstly, the periportal zonation of both glycogen synthase and the oxidative phosphorylation enzymes meant that the

Uso Del Condón en Adolescentes Nahuas, un Modelo Explicativo.

PubMed

Tirado, María de Los Ángeles Meneses; Benavides-Torres, Raquel A; Navarro, Sergio Meneses; de la Colina, Juan Antonio Doncel; Rodríguez, Dora Julia Onofre; Hernández, Francisco Javier Baéz

2018-03-01

En México, la población indígena supera los siete millones de habitantes, en Puebla el grupo más representativo es el Náhuatl. Sin embargo, las condiciones de vida, salud, educación y transporte son precarias para esta población. En los adolescentes, las responsabilidades como el matrimonio, la familia y los compromisos ante la comunidad, favorecen conductas de riesgo sexual que dificultan su desarrollo económico, social y reproductivo. El objetivo fue proponer un modelo explicativo del uso del condón en adolescentes nahuas. Método. Bajo el marco de la teoría social cognitiva, el concepto de valores culturales de Leininger y el proceso de la sustracción teórica, se desarrolló este artículo. Se muestran las relaciones del modelo con las proposiciones y los factores que influyen en el uso del condón para este grupo específico. Finalmente, el modelo explica las variables de interés, los niveles de abstracción y las relaciones entre sí en el contexto náhuatl. El siguiente paso será implementar los indicadores empíricos para conocer el grado de influencia de los factores personales y ambientales hacia el uso del condón en adolescentes nahuas. Resultados que aportarán información para el desarrollo del conocimiento en enfermería y la reducción de riesgo sexual de esta población.

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.

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

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.

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

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.

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.

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

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.

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.

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.

Factor Structure of the "Escala de Autoeficacia para la Depresion en Adolescentes" (EADA)

ERIC Educational Resources Information Center

Diaz-Santos, Mirella; Cumba-Aviles, Eduardo; Bernal, Guillermo; Rivera-Medina, Carmen

2011-01-01

The current concept and measures of self-efficacy for depression in adolescents do not consider developmental and cultural aspects essential to understand and assess this construct in Latino youth. We examined the factor structure of the "Escala de Autoeficacia para la Depresion en Adolescentes" (EADA), a Spanish instrument designed to…

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.

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

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.

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

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.

La mortalidad en adolescentes con cáncer: características clinicoepidemiológicas de muerte y aspectos éticos emergentes.

PubMed

Cicero-Oneto, Carlo Egysto; Mata-Valderrama, Guadalupe; Valdez-Martínez, Edith

Describir los aspectos epidemiológicos, clínicos y éticos de la mortalidad de los adolescentes con cáncer en -México. Se revisaron 63 expedientes clínicos de adolescentes (de 14 a 18 años de edad) con cáncer, fallecidos entre 2011 y 2014, para obtener información clínica y epidemiológica de su muerte. Los sitios de estudio fueron tres hospitales de concentración en la Ciudad de México. De los 40 adolescentes con criterios de fase terminal, 16 (40%) continuaron recibiendo tratamiento con fines curativos. De los 51 cuyo lugar de muerte era conocido, 45 (88%) murieron en hospital. De los 41 que murieron dentro de los 30 días de su última hospitalización, las muertes fueron principalmente debidas a complicaciones (51%), a progresión de la enfermedad (41%) o bien fueron muertes en tratamiento paliativo (7%, 3/41). La práctica oncológica descansa en lo que es conocido como modelo biomédico. Los resultados del estudio sugieren y apoyan la urgente necesidad de implementar verdaderos servicios de cuidados paliativos, pero más importante que eso, está el ímpetu de poner la ética de la práctica clínica en acción, y de ese modo reforzar la buena práctica de la medicina. Copyright: © 2018 SecretarÍa de Salud

CORRELATION OF NON-ALCOHOLIC FATTY LIVER DISEASE AND FEATURES OF METABOLIC SYNDROME IN MORBIDLY OBESE PATIENTS IN THE PREOPERATIVE ASSESSMENT FOR BARIATRIC SURGERY.

PubMed

Barros, Fernando de; Setúbal, Sergio; Martinho, José Manoel; Ferraz, Loraine; Gaudêncio, Andressa

2016-01-01

Obesity is an epidemic and chronic disease that can bring other comorbidities to the patient. Non-alcoholic fatty liver disease is present in up to 90% of these patients and can progress to hepatitis and hepatocarcinoma. The relationship of this liver disease and obesity is already well known; however, it is possible that some parameters of the comorbidities are more related than others in the pathophysiology of the disease. Was analyzed the relationship between non-alcoholic fatty liver disease (NAFLD) and the comorbidities of metabolic syndrome in morbidly obese patients. Was involved ultrasonography and laboratory assessment of obese patients before bariatric surgery. NAFLD was assessed using the same sonography parameters for all patients. Based on the results, the patients were divided into groups with and without NAFLD. Comparisons between them involved clinical and laboratory variables such as fasting blood glucose, insulin, HOMA-IR (homeostasis model assessment - insulin resistance), glycated hemoglobin, total cholesterol and fractions, triglycerides, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, C-reactive protein, albumin and ferritin. Patients who reported alcohol abuse (defined as the consumption of >14 drinks per week) or who had hepatitis were excluded. Eighty-two patients (74 women and 8 men) were studied, of whom 53 (64.6%) had NAFLD and 29 (35.4%) did not. The levels of glycated hemoglobin (p=0.05) and LDL cholesterol (p=0.01) were significantly altered in patients with NAFLD. However, weight, body mass index and excess weight did not differ significantly between the groups (p=0.835, p=0.488 and p=0.727, respectively). Altered LDL cholesterol and glycated hemoglobin levels were related to the presence of NAFLD. A obesidade é doença epidêmica e crônica que pode trazer outras comorbidades ao paciente. A doença hepática gordurosa não alcoólica está presente em até 90% desses pacientes e pode evoluir para

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

Los “puntos débiles o sensibles” de los Ensayos Clínicos en niñas/os y adolescentes

PubMed Central

Melamed, Irene N.

2017-01-01

Resumen La revisión ética de un Ensayo Clínico1 que incluye a niñas/os y adolescentes en calidad de participantes, debe centrar su mirada en aspectos relacionados con la vulnerabilidad inherente a esa etapa de la vida, condición que se nutre de elementos biológicos, emocionales, de justicia y de equidad, entre otros. Sin embargo, la visión sugerida en este caso y sin desoír las características mencionadas, es la que busca profundizar en uno de los actores del proceso de investigación: el Ensayo Clínico. El objetivo es poder determinar la presencia o no de “zonas frágiles o de puntos débiles” en su interior, los que al ser individualizados y especialmente considerados, contribuyan a mejorar la calidad de la revisión ética de las investigaciones que son llevadas a cabo en niñas/os y adolescentes. PMID:28757905

Etude du pronostic maternel et périnatal au cours de l’accouchement chez l’adolescente à Lubumbashi, République Démocratique du Congo

PubMed Central

Luhete, Prosper Kakudji; Mukuku, Olivier; Tambwe, Albert Mwembo; Kayamba, Prosper Kalenga Muenze

2017-01-01

Introduction L’objectif de cette étude était de déterminer la fréquence et d’évaluer le pronostic maternel et périnatal lors de l’accouchement chez les adolescentes dans la ville de Lubumbashi. Méthodes C’était une étude cas-témoin des accouchées d’une grossesse monofoetale de Décembre 2013 à Mai 2014 dans 10 maternités de référence à Lubumbashi (RD Congo). Les adolescentes (< 20 ans) ont été comparées aux femmes âgées de 20-34 ans. Les paramètres sociodémographiques maternels, la morbi-mortalité maternelle et périnatale ont été analysées. Les statistiques usuelles et la régression logistique ont été utilisées pour analyser les résultats. Le seuil de signification a été fixé à une valeur de p<0,05. Résultats La fréquence d’accouchement chez les adolescentes était de 7,7%. Nous avons observé que la césarienne (ORa=1,9 (1,1-3,1)), l’épisiotomie (ORa=4,2 (2,9-5,9)), la délivrance pathologique (ORa= 2,7 (1,1-6,5)), l’éclampsie (ORa= 4,4 (1,3-14,5)) et le faible poids de naissance (ORa=2,0 (1,3-3,0)) ont été significativement plus élevés chez les adolescentes que chez les adultes. Conclusion L’accouchement chez les adolescentes, comparativement à celui de femmes âgées de 20-34 ans, reste associé à un mauvais pronostic. D’où l’organisation des séances de sensibilisation pour une meilleure fréquentation des services consultations prénatales, une optimisation du dépistage, de la surveillance et de la prévention des pathologies de la grossesse chez les adolescentes s’avère importante et urgente. Introduction This study aimed to determine the frequency and to assess maternal and perinatal prognosis for vaginal delivery in adolescent girls in the city of Lubumbashi. Methods We conducted a case-control study of vaginal deliveries in singleton pregnancy in 10 referral hospitals in Lubumbashi (DR Congo) from December 2013 to May 2014. Adolescent girls (< 20 years) were compared to older women

[Validity and reproducibility of Escala de Evaluación da Insatisfación Corporal para Adolescentes].

PubMed

Conti, Maria Aparecida; Slater, Betzabeth; Latorre, Maria do Rosário Dias de Oliveira

2009-06-01

To validate a body dissatisfaction scale for adolescents. The study included 386 female and male adolescents aged 10 to 17 years enrolled in a private elementary and middle school in the city of São Bernardo do Campo, southeastern Brazil, in 2006. 'Escala de Evaluación da Insatisfación Corporal para Adolescentes' (body dissatisfaction scale for adolescents) was translated and culturally adapted. The Portuguese instrument was evaluated for internal consistency using Cronbach's alpha, factor analysis with Varimax rotation, discriminant validity by comparing score means according to nutritional status (low weight, normal weight, and at risk of overweight and obesity) using the Kruskal-Wallis test. Concurrent validity was assessed using Spearman's rank correlation coefficient between scores and body mass index, waist-hip ratio and waist circumference. Reproducibility was evaluated using Wilcoxon test, and intraclass correlation coefficient. The translated and back-translated scale showed good agreement with the original one. The translated scale had good internal consistency in all subgroups studied (males and females in early and intermediate adolescence) and was able to discriminate adolescents according to their nutritional status. In the concurrent analysis, all three measures were correlated, except for males in early adolescence. Its reproducibility was ascertained. The 'Escala de Evaluación da Insatisfación Corporal para Adolescentes' was successfully translated into Portuguese and adapted to the Brazilian background and showed good results. It is recommended for the evaluation of the attitudinal component of body image in adolescents.

EM Diffusion for a Time-Domain Airborne EM System

NASA Astrophysics Data System (ADS)

Yin, C.; Qiu, C.; Liu, Y.; Cai, J.

2014-12-01

Visualization of EM diffusion for an airborne EM (AEM) system is important for understanding the transient procedure of EM diffusion. The current distribution and diffusion features also provide effective means to evaluate EM footprint, depth of exploration and further help AEM system design and data interpretation. Most previous studies on EM diffusion (or "smoke ring" effect) are based on the static presentation of EM field, where the dynamic features of EM diffusion were not visible. For visualizing the dynamic feature of EM diffusion, we first calculate in this paper the frequency-domain EM field by downward continuation of the EM field at the EM receiver to the deep earth. After that, we transform the results to time-domain via a Fourier transform. We take a homogeneous half-space and a two-layered earth induced by a step pulse to calculate the EM fields and display the EM diffusion in the earth as 3D animated vectors or time-varying contours. The "smoke ring" effect of EM diffusion, dominated by the resistivity distribution of the earth, is clearly observed. The numerical results for an HCP (vertical magnetic dipole) and a VCX (horizontal magnetic dipole) transmitting coil above a homogeneous half-space of 100 ohm-m are shown in Fig.1. We display as example only the distribution of EM field inside the earth for the diffusion time of 0.05ms. The detailed EM diffusion will be shown in our future presentation. From the numerical experiments for different models, we find that 1) the current for either an HCP or a VCX transmitting dipole propagates downward and outward with time, becoming wider and more diffuse, forming a "smoke ring"; 2) for a VCX transmitter, the underground current forms two ellipses, corresponding to the two polarities of the magnetic flux of a horizontal magnetic dipole, injecting into or ejected from the earth; 3) for a HCP transmitter, however, the underground current forms only one circle, corresponding to the polarity of the magnetic flux

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.

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

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.

Busca de estruturas em grandes escalas em altos redshifts

NASA Astrophysics Data System (ADS)

Boris, N. V.; Sodré, L., Jr.; Cypriano, E.

2003-08-01

A busca por estruturas em grandes escalas (aglomerados de galáxias, por exemplo) é um ativo tópico de pesquisas hoje em dia, pois a detecção de um único aglomerado em altos redshifts pode por vínculos fortes sobre os modelos cosmológicos. Neste projeto estamos fazendo uma busca de estruturas distantes em campos contendo pares de quasares próximos entre si em z Â3 0.9. Os pares de quasares foram extraídos do catálogo de Véron-Cetty & Véron (2001) e estão sendo observados com os telescópios: 2,2m da University of Hawaii (UH), 2,5m do Observatório de Las Campanas e com o GEMINI. Apresentamos aqui a análise preliminar de um par de quasares observado nos filtros i'(7800 Å) e z'(9500 Å) com o GEMINI. A cor (i'-z') mostrou-se útil para detectar objetos "early-type" em redshifts menores que 1.1. No estudo do par 131046+0006/J131055+0008, com redshift ~ 0.9, o uso deste método possibilitou a detecção de sete objetos candidatos a galáxias "early-type". Num mapa da distribuição projetada dos objetos para 22 < i' < 25 observou-se que estas galáxias estão localizadas próximas a um dos quasares e há indícios de que estejam aglomeradas dentro de um área de ~ 6 arcmin2. Se esse for o caso, estes objetos seriam membros de uma estrutura em grande escala. Um outro argumento em favor dessa hipótese é que eles obedecem uma relação do tipo Kormendy (raio equivalente X brilho superficial dentro desse raio), como a apresentada pelas galáxias elípticas em z = 0.

Metabolic markers and ALT cutoff level for diagnosing nonalcoholic fatty liver disease: a community-based cross-sectional study.

PubMed

Miyake, Teruki; Kumagi, Teru; Hirooka, Masashi; Koizumi, Mitsuhito; Furukawa, Shinya; Ueda, Teruhisa; Tokumoto, Yoshio; Ikeda, Yoshio; Abe, Masanori; Kitai, Kohichiro; Hiasa, Yoichi; Matsuura, Bunzo; Onji, Morikazu

2012-06-01

Untreated nonalcoholic fatty liver disease (NAFLD) may progress to liver cirrhosis or failure and is associated with the development of hepatocellular carcinoma, diabetes, and cardiovascular disease. It is therefore essential to diagnose and treat NAFLD at an early stage. To assist in this effort, this retrospective study explored the risk factors for NAFLD, and derived new surrogates, a revised alanine aminotransferase (ALT) cutoff level and a novel NAFLD index, to identify previously undiagnosed cases of NAFLD. Using a community-based, cross-sectional design, the records of 6,370 Japanese subjects who had undergone at least 1 annual health check-up were reviewed for the identification of subjects meeting the diagnostic criteria for NAFLD and the variables associated with NAFLD for the estimation of ideal ALT cutoff levels. The results of multivariate analysis of the 1,346 subjects who met the diagnostic criteria for NAFLD confirmed that metabolic disease markers and a novel NAFLD index, using the variables derived from multivariate analysis, were also markers of NAFLD. The ALT cutoff levels for NAFLD diagnosis were estimated at 25 U/L for males and 17 U/L for females. ALT level and the novel NAFLD index were confirmed to be surrogate markers for NAFLD in addition to metabolic disease markers. The ALT cutoff level used in NAFLD diagnosis should be revised downward to identify subjects at risk of NAFLD to prevent NAFLD progression and the development of associated diseases.

[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.

Evaluation of Biomarkers in Egyptian Patients with Different Grades of Nonalcoholic Fatty Liver Disease.

PubMed

Borai, Ibrahim H; Shaker, Yehia; Kamal, Maha Moustafa; Ezzat, Wafaa M; Ashour, Esmat; Afify, Mie; Gouda, Weaam; Elbrashy, Maha M

2017-06-28

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a silent disease; its spectrum includes simple steatosis, nonalcoholic steatohepatitis and fibrosis. Pro- and anti-inflammatory cytokines play roles in the pathogenesis of NAFLD and insulin resistance (IR). Moreover, plasma cell antigen-1 (PC-1) is related to IR and associated with NAFLD progression. Therefore, we aimed to detect biomarkers, ultrasonographic and anthropometric findings capable of differentiating NAFLD grades, since most previous investigators were concerned more with NAFLD patients without classifying them into grades. Methods: A total of 87 NAFLD patients (31 with grade 1 (mild NAFLD), 26 with grade 2 (moderate NAFLD) and 30 with grade 3 (severe NAFLD) were included in the study, in addition to 47 controls (grade 0). All subjects underwent ultrasonographic examination for NAFLD diagnosis. Serum interleukin-10 (IL-10), plasma interleukin-18 (IL-18) and plasma PC-1 levels were determined using enzyme-linked immunosorbent assay. Results: Homoeostasis model assessment (HOMA)-IR was higher in different NAFLD grades than in controls. Ultrasonographic and anthropometric findings and lipid profile indices (except for high-density lipoprotein cholesterol, which was decreased) were increased with NAFLD progression. Grade 3 patients showed significant increase in levels of IL-18 and significant decrease in IL-10 and PC-1 levels when compared to grade 1 patients. Conclusion: Anthropometric and ultrasonographic findings were valuable in differentiating NAFLD grades. IR is very important in NAFLD pathogenesis. IL-18, HOMA-index and PC-1 levels could be used to differentiate between NAFLD grades, together with other measurements.

Evaluation of Biomarkers in Egyptian Patients with Different Grades of Nonalcoholic Fatty Liver Disease

PubMed Central

Borai, Ibrahim H.; Shaker, Yehia; Kamal, Maha Moustafa; Ezzat, Wafaa M.; Ashour, Esmat; Afify, Mie; Gouda, Weaam; Elbrashy, Maha M.

2017-01-01

Abstract Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a silent disease; its spectrum includes simple steatosis, nonalcoholic steatohepatitis and fibrosis. Pro- and anti-inflammatory cytokines play roles in the pathogenesis of NAFLD and insulin resistance (IR). Moreover, plasma cell antigen-1 (PC-1) is related to IR and associated with NAFLD progression. Therefore, we aimed to detect biomarkers, ultrasonographic and anthropometric findings capable of differentiating NAFLD grades, since most previous investigators were concerned more with NAFLD patients without classifying them into grades. Methods: A total of 87 NAFLD patients (31 with grade 1 (mild NAFLD), 26 with grade 2 (moderate NAFLD) and 30 with grade 3 (severe NAFLD) were included in the study, in addition to 47 controls (grade 0). All subjects underwent ultrasonographic examination for NAFLD diagnosis. Serum interleukin-10 (IL-10), plasma interleukin-18 (IL-18) and plasma PC-1 levels were determined using enzyme-linked immunosorbent assay. Results: Homoeostasis model assessment (HOMA)-IR was higher in different NAFLD grades than in controls. Ultrasonographic and anthropometric findings and lipid profile indices (except for high-density lipoprotein cholesterol, which was decreased) were increased with NAFLD progression. Grade 3 patients showed significant increase in levels of IL-18 and significant decrease in IL-10 and PC-1 levels when compared to grade 1 patients. Conclusion: Anthropometric and ultrasonographic findings were valuable in differentiating NAFLD grades. IR is very important in NAFLD pathogenesis. IL-18, HOMA-index and PC-1 levels could be used to differentiate between NAFLD grades, together with other measurements. PMID:28660148

RETOS EN LA INTERVENCIÓN CON ADOLESCENTES PUERTORRIQUEÑOS/AS QUE MANIFIESTAN COMPORTAMIENTO SUICIDA*

PubMed Central

Vélez, Yovanska Duarté; Dávila, Paloma Torres; Hernández, Samariz Laboy

2015-01-01

Presentamos un estudio de caso de una adolescente puertorriqueña con comportamiento suicida. Esta comenzó una Terapia Socio Cognitivo-Conductual para el Comportamiento Suicida (TSCC-CS) de tipo ambulatorio luego de una hospitalización por intento suicida. La TSCC-CS incorpora una perspectiva ecológica y de desarrollo a la terapia cognitivo-conductual. Inicialmente mostró baja autoestima y severos síntomas depresivos y de ansiedad. Al finalizar el tratamiento, manifestó un cambio significativo en su sintomatología clínica y evidenció una mejoría en sus destrezas de manejo. No presentó ideas suicidas durante meses previos, ni durante el seguimiento. El análisis de este caso permitió realizar cambios en el protocolo de tratamiento, particularmente en las sesiones de familia y de comunicación con el fin de aumentar la viabilidad del tratamiento. PMID:26702337

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.

Non-alcoholic Fatty Liver Disease in Lean Subjects: Characteristics and Implications.

PubMed

Kumar, Ramesh; Mohan, Shantam

2017-09-28

Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in obese subjects; however, it is not rare among lean individuals. Given the absence of traditional risk factors, it tends to remain under-recognised. The metabolic profiles of lean NAFLD patients are frequently comparable to those of obese NAFLD patients. Though results from several studies have been mixed, it has been generally revealed that lean subjects with NAFLD have minor insulin resistance compared to that in obese NAFLD. Several genetic variants are associated with NAFLD without insulin resistance. Some data suggest that the prevalence of steatohepatitis and advanced fibrosis do not differ significantly between lean and obese NAFLD; however, the former tend to have less severe disease at presentation. The underlying pathophysiology of lean NAFLD may be quite different. Genetic predispositions, fructose- and cholesterol-rich diet, visceral adiposity and dyslipidaemia have potential roles in the pathogenic underpinnings. Lean NAFLD may pose a risk for metabolic disturbances, cardiovascular morbidity or overall mortality. Secondary causes of hepatic steatosis are also needed to be ruled out in lean subjects with NAFLD. The effectiveness of various treatment modalities, such as exercise and pharmacotherapy, on lean NAFLD is not known. Weight loss is expected to help lean NAFLD patients who have visceral obesity. Further investigation is needed for many aspects of lean NAFLD, including mechanistic pathogenesis, risk assessment, natural history and therapeutic approach.

Non-alcoholic Fatty Liver Disease in Lean Subjects: Characteristics and Implications

PubMed Central

Kumar, Ramesh; Mohan, Shantam

2017-01-01

Abstract Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in obese subjects; however, it is not rare among lean individuals. Given the absence of traditional risk factors, it tends to remain under-recognised. The metabolic profiles of lean NAFLD patients are frequently comparable to those of obese NAFLD patients. Though results from several studies have been mixed, it has been generally revealed that lean subjects with NAFLD have minor insulin resistance compared to that in obese NAFLD. Several genetic variants are associated with NAFLD without insulin resistance. Some data suggest that the prevalence of steatohepatitis and advanced fibrosis do not differ significantly between lean and obese NAFLD; however, the former tend to have less severe disease at presentation. The underlying pathophysiology of lean NAFLD may be quite different. Genetic predispositions, fructose- and cholesterol-rich diet, visceral adiposity and dyslipidaemia have potential roles in the pathogenic underpinnings. Lean NAFLD may pose a risk for metabolic disturbances, cardiovascular morbidity or overall mortality. Secondary causes of hepatic steatosis are also needed to be ruled out in lean subjects with NAFLD. The effectiveness of various treatment modalities, such as exercise and pharmacotherapy, on lean NAFLD is not known. Weight loss is expected to help lean NAFLD patients who have visceral obesity. Further investigation is needed for many aspects of lean NAFLD, including mechanistic pathogenesis, risk assessment, natural history and therapeutic approach. PMID:28936403

Fertility rates and perinatal outcomes of adolescent pregnancies: a retrospective population-based study.

PubMed

Souza, Maria de Lourdes de; Lynn, Fiona Ann; Johnston, Linda; Tavares, Eduardo Cardoso Teixeira; Brüggemann, Odaléa Maria; Botelho, Lúcio José

2017-04-06

analyze trends in fertility rates and associations with perinatal outcomes for adolescents in Santa Catarina, Brazil. a population-based study covering 2006 to 2013 was carried out to evaluate associations between perinatal outcomes and age groups, using odds ratios, and Chi-squared tests. differences in the fertility rate among female adolescents across regions and time period were observed, ranging from 40.9 to 72.0 per 1,000 in mothers aged 15-19 years. Adolescents had fewer prenatal care appointments than mothers ≥20 years, and a higher proportion had no partner. Mothers aged 15-19 years were more likely to experience preterm birth (OR:1.1; CI:1.08-1.13; p<0.001), have an infant with low birthweight (OR:1.1; CI:1.10-1.15; p<0.001) and low Apgar score at 5 minutes (OR:1.4; CI:1.34-1.45; p<0.001) than mothers ≥20 years, with the odds for adverse outcomes greater for those aged 10-14 years. this study provides evidence of fertility rates among adolescents remaining higher in regions of social and economic deprivation. Adolescent mothers and their infants more likely to experience adverse perinatal outcomes. Nurses, public health practitioners, health and social care professionals and educators need to work collaboratively to better target strategies for adolescents at greater risk; to help reduce fertility rates and improve outcomes. analizar as tendências das taxas de fertilidade e associações com desfechos perinatais entre adolescentes em Santa Catarina, Brasil. estudo populacional conduzido de 2016 à 2013. Associações entre desfechos perinatais e grupos por faixa etária foram investigadas usando odds Ratio e teste Chi-quadrado. as diferenças encontradas nas taxas de fertilidade entre mães adolescentes nas regiões e período observado variaram de 40,9-72,0 por 1.000 entre mães de 15 a 19 anos de idade. As adolescentes atenderam menos consultas pré-natais, quando comparadas às mães com 20 anos ou mais, e a maioria não tinha parceiro. M�

Correlation of the NBME advanced clinical examination in EM and the national EM M4 exams.

PubMed

Hiller, Katherine; Miller, Emily S; Lawson, Luan; Wald, David; Beeson, Michael; Heitz, Corey; Morrissey, Thomas; House, Joseph; Poznanski, Stacey

2015-01-01

Since 2011 two online, validated exams for fourth-year emergency medicine (EM) students have been available (National EM M4 Exams). In 2013 the National Board of Medical Examiners offered the Advanced Clinical Examination in Emergency Medicine (EM-ACE). All of these exams are now in widespread use; however, there are no data on how they correlate. This study evaluated the correlation between the EM-ACE exam and the National EM M4 Exams. From May 2013 to April 2014 the EM-ACE and one version of the EM M4 exam were administered sequentially to fourth-year EM students at five U.S. medical schools. Data collected included institution, gross and scaled scores and version of the EM M4 exam. We performed Pearson's correlation and random effects linear regression. 305 students took the EM-ACE and versions 1 (V1) or 2 (V2) of the EM M4 exams (281 and 24, respectively) [corrected].The mean percent correct for the exams were as follows: EM-ACE 74.9 (SD-9.82), V1 83.0 (SD-6.39), V2 78.5 (SD-7.70) [corrected]. Pearson's correlation coefficient for the V1/EM-ACE was 0.53 (0.43 scaled) and for the V2/EM-ACE was 0.58 (0.41 scaled) [corrected]. The coefficient of determination for V1/ EM-ACE was 0.73 and for V2/EM-ACE 0.71 (0.65 and .49 for scaled scores) [ERRATUM]. The R-squared values were 0.28 and 0.30 (0.18 and 0.13 scaled), respectively [corrected]. There was significant cluster effect by institution. There was moderate positive correlation of student scores on the EM-ACE exam and the National EM M4 Exams.

The impact of non-alcoholic fatty liver disease on incident type 2 diabetes mellitus in non-overweight individuals.

PubMed

Fukuda, Takuya; Hamaguchi, Masahide; Kojima, Takao; Hashimoto, Yoshitaka; Ohbora, Akihiro; Kato, Takahiro; Nakamura, Naoto; Fukui, Michiaki

2016-02-01

The aim of this study was to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on incident type 2 diabetes mellitus (T2DM) in non-overweight individuals with NAFLD. A population-based retrospective cohort study of 4629 participants who were enrolled in a health check-up programme for more than 10 years. A standardized questionnaire and abdominal ultrasonography were used to diagnose NAFLD. A cut-off point of BMI 23 kg/m(2) was used to define overweight (≥23.0 kg/m(2)) or non-overweight (<23.0 kg/m(2)). The primary outcome was incident T2DM. Over a mean follow-up of 12.8 years, 351 participants (7.6%) developed T2DM. The incidence rate of T2DM was 3.2% in the non-overweight without NAFLD group, 14.4% in the non-overweight with NAFLD group, 8.0% in the overweight without NAFLD group and 26.4% in the overweight with NAFLD group. The adjusted hazard ratios for incident T2DM compared with the non-overweight without NAFLD group were as follows: 3.59 (95% CI: 2.14-5.76) in the non-overweight with NAFLD group, 1.99 (95% CI: 1.47-2.69) in the overweight without NAFLD group and 6.77 (95% CI: 5.17-8.91) in the overweight with NAFLD group. The adjusted hazard ratio in the non-overweight with NAFLD group was significantly higher than that in the overweight without NAFLD group or that in the non-overweight without NAFLD group. Non-overweight individuals with NAFLD had a high risk of incident T2DM. Diagnosis of NAFLD is important in non-overweight individuals, and therefore it might be necessary to follow their health conditions on a long-term basis after detection of NAFLD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Differential Impact of Weight Loss on Nonalcoholic Fatty Liver Resolution in a North American Cohort with Obesity.

PubMed

Rachakonda, Vikrant; Wills, Rachel; DeLany, James P; Kershaw, Erin E; Behari, Jaideep

2017-08-01

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. In this study, a North American cohort with obesity enrolled in a lifestyle modification program was examined to determine the impact of weight loss on NAFLD resolution and sarcopenia. Nondiabetic individuals with World Health Organization Class II/III obesity enrolled in a 6-month weight loss intervention were included. Steatosis was measured using computed tomography (CT)-derived liver:spleen attenuation ratio. Body composition was assessed using dual X-ray absorptiometry, air-displacement plethysmography, and CT anthropometry. At baseline, participants with NAFLD had greater visceral adipose tissue (VAT) but similar skeletal muscle area compared to those without NAFLD. After intervention, weight loss was similar in the two groups, but participants with NAFLD lost more VAT than those without NAFLD (-38.81 [-55.98 to -21.63] cm 2 vs. -13.82 [-29.65 to -2.02] cm 2 ; P = 0.017). In the subset with NAFLD at baseline, participants with NAFLD resolution after intervention lost more VAT than those with persistent NAFLD (-57.23 [-88.63 to -25.84) cm 2 vs. -26.92 [-52.14 to -26.92] cm 2 , P = 0.039). In a Western cohort with obesity, NAFLD was not associated with sarcopenia. After lifestyle modification, there was a differential impact on NAFLD resolution, with twofold greater VAT loss in participants who resolved NAFLD compared with those with persistent NAFLD despite similar weight loss. © 2017 The Obesity Society.

Non-alcoholic fatty liver disease and dyslipidemia: An update.

PubMed

Katsiki, Niki; Mikhailidis, Dimitri P; Mantzoros, Christos S

2016-08-01

Non-alcoholic fatty liver (NAFLD) is the most common liver disease worldwide, progressing from simple steatosis to necroinflammation and fibrosis (leading to non-alcoholic steatohepatitis, NASH), and in some cases to cirrhosis and hepatocellular carcinoma. Inflammation, oxidative stress and insulin resistance are involved in NAFLD development and progression. NAFLD has been associated with several cardiovascular (CV) risk factors including obesity, dyslipidemia, hyperglycemia, hypertension and smoking. NAFLD is also characterized by atherogenic dyslipidemia, postprandial lipemia and high-density lipoprotein (HDL) dysfunction. Most importantly, NAFLD patients have an increased risk for both liver and CV disease (CVD) morbidity and mortality. In this narrative review, the associations between NAFLD, dyslipidemia and vascular disease in NAFLD patients are discussed. NAFLD treatment is also reviewed with a focus on lipid-lowering drugs. Finally, future perspectives in terms of both NAFLD diagnostic biomarkers and therapeutic targets are considered. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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.

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.

EMS provider determinations of necessity for transport and reimbursement for EMS response, medical care, and transport: combined resource document for the National Association of EMS Physicians position statements.

PubMed

Millin, Michael G; Brown, Lawrence H; Schwartz, Brian

2011-01-01

With increasing demands for emergency medical services (EMS), many EMS jurisdictions are utilizing EMS provider-initiated nontransport policies as a method to offload potentially nonemergent patients from the EMS system. EMS provider determination of medical necessity, resulting in nontransport of patients, has the potential to avert unnecessary emergency department visits. However, EMS systems that utilize these policies must have additional education for the providers, a quality improvement process, and active physician oversight. In addition, EMS provider determination of nontransport for a specific situation should be supported by evidence in the peer-reviewed literature that the practice is safe. Further, EMS systems that do not utilize these programs should not be financially penalized. Payment for EMS services should be based on the prudent layperson standard. EMS systems that do utilize nontransport policies should be appropriately reimbursed, as this represents potential cost savings to the health care system.

The persistence of fatty liver has a differential impact on the development of diabetes: The Kangbuk Samsung Health Study.

PubMed

Bae, Ji Cheol; Han, Ji Min; Cho, Jung Hwan; Kwon, Hyemi; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Kwon, Sam; Park, Sung-Woo; Rhee, Eun Jung

2018-01-01

To evaluate whether variable fatty liver status over time influence the risk of type 2 diabetes differently. We analyzed the data from 7849 subjects without type 2 diabetes who underwent comprehensive health check-ups annually for 5 years. All subjects had an abdominal ultrasonography annually. The risk of incident diabetes was assessed in individuals with sustained non-alcoholic fatty liver disease (NAFLD), individuals with changed fatty liver status (intermittent NAFLD group), and individuals who did not have NAFLD (never NAFLD group) during the study period. A subgroup analysis was done in subjects of the intermittent NAFLD group. Incident diabetes was compared according to the number of time diagnosed as NAFLD by annual ultrasonography. During the mean follow-up of 4 years, subjects in the sustained NAFLD group had a HR of 1.50 (95% CI 1.13-1.98) for the development of diabetes compared with those in the never NAFLD group, whereas the risk was not higher in the intermittent NAFLD group (HR 0.99, 95% CI 0.76-1.31). When compared with the intermittent NAFLD group, multivariable adjusted HR for incident diabetes was 1.50 (95% CI 1.20-1.89) in the sustained NAFLD group. As the number of times diagnosed as NAFLD increased, the proportion of subjects who developed diabetes also increased (p = .002). The presence of fatty liver was differentially associated with incident diabetes based on its duration. The persistence of fatty liver status is an important factor for an independent association between NAFLD and incident diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypertriglyceridemic Waist Phenotype and Changes in the Fasting Glycemia and Blood Pressure in Children and Adolescents Over One-Year Follow-Up Period.

PubMed

Costa, Priscila Ribas de Farias; Assis, Ana Marlúcia Oliveira; Cunha, Carla de Magalhães; Pereira, Emile Miranda; Jesus, Gabriela Dos Santos de; Silva, Lais Eloy Machado da; Alves, Wilanne Pinheiro de Oliveira

2017-07-01

The hypertriglyceridemic waist (HTW) phenotype is defined as the simultaneous presence of increased waist circumference (WC) and serum triglycerides (TG) levels and it has been associated with cardiometabolic risk in children and adolescents. The objective was to evaluate the influence of HTW phenotype in the fasting glycemia and blood pressure in children and adolescents over one-year follow-up period. It is a cohort study involving 492 children and adolescents from 7 to 15 years old, both genders, who were submitted to anthropometric, biochemical and clinical evaluation at the baseline, and also after 6 and 12 months of follow-up. Generalized Estimating Equation (GEE) models were calculated to evaluate the longitudinal influence of the HTW phenotype in the glycemia and blood pressure over one-year. It was observed a prevalence of 10.6% (n = 52) of HTW phenotype in the students. The GEE models identified that students with HTW phenotype had an increase of 3.87 mg/dl in the fasting glycemia mean (CI: 1.68-6.05) and of 3.67mmHg in the systolic blood pressure (SBP) mean (CI: 1.55-6.08) over one-year follow-up, after adjusting for confounding variables. The results of this study suggest that HTW phenotype is a risk factor for longitudinal changes in glycemia and SBP in children and adolescents over one-year follow-up period. O fenótipo de cintura hipertrigliceridêmica (CHT) é definido como a presença simultânea de circunferência de cintura (CC) e níveis séricos de triglicérides (TG) aumentados e tem sido associado com risco cardiometabólico em crianças e adolescentes. Avaliar a influência do fenótipo CHT na glicemia de jejum e na pressão arterial em crianças e adolescentes em um período de acompanhamento de um ano. Trata-se de um estudo de coorte envolvendo 492 crianças e adolescentes de 7 a 15 anos de ambos os sexos, que foram submetidos à avaliação antropométrica, bioquímica e clínica no início e também após 6 e 12 meses de seguimento. Os

Relationship between obesity, metabolic syndrome, and nonalcoholic fatty liver disease in the elderly agricultural and fishing population of Taiwan.

PubMed

Shen, Hsi-Che; Zhao, Zi-Hao; Hu, Yi-Chun; Chen, Yu-Fen; Tung, Tao-Hsin

2014-01-01

The purpose of this study was to explore the relationship between obesity, the metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) in the elderly agricultural and fishing population of Taipei, Taiwan. The study participants comprised 6,511 (3,971 male and 2,540 female) healthy elderly subjects voluntarily attending a teaching hospital for a physical check-up in 2010. Blood samples and real-time ultrasound-proven fatty liver sonography results were collected. The prevalence of NAFLD in this elderly population was 27.2%, including mild NAFLD (16.0%), moderate NAFLD (10.3%), and severe NAFLD (0.9%). The prevalence of moderate or severe NAFLD for metabolic syndrome proved to be substantially greater (P<0.0001, χ(2) test) for one or two metabolic factors. Using multinomial logistic regression analysis, age, sex, metabolic syndrome, and higher body mass index had a statistically significant association with mild NAFLD. Age, sex, metabolic syndrome, higher body mass index, and higher alanine aminotransferase were significantly related to moderate NAFLD. In addition, higher body mass index, higher uric acid, and higher alanine aminotransferase levels were significantly related to severe NAFLD. The sensitivity and specificity of body mass index and waist circumference as markers of NAFLD were estimated to be 81% and 84%, respectively, and 77% and 69%, respectively. The prevalence of mild or moderate NAFLD was related to obesity and metabolic syndrome. Higher body mass index was also related to severe NAFLD but not to metabolic syndrome. Targeting this population for control of obesity and improved metabolic function is important.

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.

A Case-control Study to Evaluate the Prevalence of Nonalcoholic Fatty Liver Disease Among Patients with Moderate-to-severe Psoriasis.

PubMed

Awosika, Olabola; Eleryan, Misty G; Rengifo-Pardo, Monica; Doherty, Lindsay; Martin, Lisa W; Ehrlich, Alison

2018-06-01

Objective: International case-control studies have demonstrated that psoriasis is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). The purpose of the present study was to establish an association of psoriasis and NAFLD in patients attending a dermatology clinic center in the United States. Design: This was an observational, case-control study. Setting: The study setting was an outpatient dermatology clinic of the George Washington Medical Faculty Associates in Washington DC. Participants: One hundred fifty-one adult patients with psoriasis and 51 control subjects were recruited. Measurements: NAFLD was diagnosed by ultrasonography after excluding secondary causes of liver disease. Regression analysis was used to assess the associations between: 1) NAFLD and psoriasis and 2) metabolic syndrome components and NAFLD among psoriasis patients. Results: NAFLD was more prevalent in patients with psoriasis (21.2% vs. 7.8%, p <0.04). However, psoriasis was not associated with NAFLD when matching for age, sex, and body mass index (BMI) (odds ratio: 2.63, 95% confidence interval [CI]: 0.51-13.6; p =0.25). As compared to patients with psoriasis but without NAFLD, those with NAFLD were more likely to have obesity (BMI: 34.9 vs. 27.2, 95% CI: 32.4-37.5 vs. 25.9-28.5; p <0.01). NAFLD in patients with psoriasis was also associated with select components of metabolic syndrome, including hyperglycemia and hyperlipidemia. Conclusion: Our findings show there is an association of psoriasis with NAFLD. Our findings also suggest an increased presence of metabolic syndrome components in patients with psoriasis and NAFLD. Trial registry: NCT00930384.

Factor Structure of the Escala de Autoeficacia para la Depresión en Adolescentes (EADA)

PubMed Central

Díaz-Santos, Mirella; Cumba-Avilés, Eduardo; Bernal, Guillermo; Rivera-Medina, Carmen

2018-01-01

The current concept and measures of self-efficacy for depression in adolescents do not consider developmental and cultural aspects essential to understand and assess this construct in Latino youth. We examined the factor structure of the Escala de Autoeficacia para la Depresión en Adolescentes (EADA): a Spanish instrument designed to assess this construct as experienced by this population. Participants were 116 Puerto Rican adolescents aged 13 to 17 years who completed the EADA and two other self-report measures. An exploratory factor analysis yielded a two-factor solution (Personal Self-Efficacy for Depression and Interpersonal Self-Efficacy for Depression) accounting for 37.57% of the total variance. Results revealed that EADA factors have excellent internal consistency as well as concurrent and construct validity, supporting its adequacy to assess Latino adolescents’ self-efficacy for depression. The conceptual meaning of the factors was consistent with the distinction between aspects of this construct hypothesized to be important among Latino youth.

Screening for non-alcoholic fatty liver disease in children: do guidelines provide enough guidance?

PubMed

Koot, B G P; Nobili, V

2017-09-01

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the industrialized world in children. Its high prevalence and important health risks make NAFLD highly suitable for screening. In practice, screening is widely, albeit not consistently, performed. To review the recommendations on screening for NAFLD in children. Recommendations on screening were reviewed from major paediatric obesity guidelines and NAFLD guidelines. A literature overview is provided on open questions and controversies. Screening for NAFLD is advocated in all obesity and most NAFLD guidelines. Guidelines are not uniform in whom to screen, and most guidelines do not specify how screening should be performed in practice. Screening for NAFLD remains controversial, due to lack of a highly accurate screening tool, limited knowledge to predict the natural course of NAFLD and limited data on its cost effectiveness. Guidelines provide little guidance on how screening should be performed. Screening for NAFLD remains controversial because not all conditions for screening are fully met. Consensus is needed on the optimal use of currently available screening tools. Research should focus on new accurate screening tool, the natural history of NAFLD and the cost effectiveness of different screening strategies in children. © 2017 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

Autonomous Microstructure EM-APEX Floats

DTIC Science & Technology

2016-01-01

Autonomous Microstructure_EM-APEX_Float 4/8/16 at 3:21 PM 1 Title: Autonomous Microstructure EM-APEX Floats Authors: Ren-Chieh Lien1,2...Street Seattle, WA 98105 rcl@uw.edu Abstract: Fast responding FP-07 thermistors have been incorporated on profiling EM-APEX floats to measure...storage board. The raw and processed temperature observations are stored on a microSD card. Results from eight microstructure EM-APEX floats

Association Between Insulin Resistance and Oxidative Stress Parameters in Obese Adolescents with Non-Alcoholic Fatty Liver Disease

PubMed Central

Pirgon, Özgür; Bilgin, Hüseyin; Çekmez, Ferhat; Kurku, Hüseyin; Dündar, Bumin Nuri

2013-01-01

Objective: Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in children. The aim of this study was to investigate the associations of oxidative stress with insulin resistance and metabolic risk factors in obese adolescents with NAFLD. Methods: Forty-six obese adolescents (23 girls and 23 boys, mean age: 12.8±2.2 years) and 29 control subjects (15 girls and 14 boys, mean age: 12.7±2.7 years) were enrolled in the study. The obese subjects were divided into two groups (NAFLD group and non-NAFLD group) based on the elevated alanine aminotransferase levels (>30 IU/L) and the presence or absence of liver steatosis detected by ultrasonography. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. Plasma total antioxidant status (TAS) and total oxidant status (TOS) level measurements (REL Assay Diagnostics) were done in all participants. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of OS. Results: Fasting insulin levels and HOMA-IR values in the NAFLD group were significantly higher than in the non-NAFLD and control groups. TAS measurements were decreased in both obese groups (NAFLD and non-NAFLD) in comparison with the control group. TOS and OSI measurements were higher in the NAFLD group than in the non-NAFLD and control groups. OSI was positively correlated with fasting insulin (r=0.67, p=0.01) and HOMA-IR (r=0.71, p=0.02) in the NAFLD obese group. Conclusions: In this cross-sectional study, elevated OS markers in obese adolescents with NAFLD were associated with insulin resistance. This data suggest that an antioxidant therapy might have a potential for treating NAFLD associated with insulin resistance. Conflict of interest:None declared. PMID:23367495

Association between insulin resistance and oxidative stress parameters in obese adolescents with non-alcoholic fatty liver disease.

PubMed

Pirgon, Özgür; Bilgin, Hüseyin; Çekmez, Ferhat; Kurku, Hüseyin; Dündar, Bumin Nuri

2013-01-01

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in children. The aim of this study was to investigate the associations of oxidative stress with insulin resistance and metabolic risk factors in obese adolescents with NAFLD. Forty-six obese adolescents (23 girls and 23 boys, mean age: 12.8 ± 2.2 years) and 29 control subjects (15 girls and 14 boys, mean age: 12.7 ± 2.7 years) were enrolled in the study. The obese subjects were divided into two groups (NAFLD group and non-NAFLD group) based on the elevated alanine aminotransferase levels (>30 IU/L) and the presence or absence of liver steatosis detected by ultrasonography. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. Plasma total antioxidant status (TAS) and total oxidant status (TOS) level measurements (REL Assay Diagnostics) were done in all participants. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of OS. Fasting insulin levels and HOMA-IR values in the NAFLD group were significantly higher than in the non-NAFLD and control groups. TAS measurements were decreased in both obese groups (NAFLD and non-NAFLD) in comparison with the control group. TOS and OSI measurements were higher in the NAFLD group than in the non-NAFLD and control groups. OSI was positively correlated with fasting insulin (r=0.67, p=0.01) and HOMA-IR (r=0.71, p=0.02) in the NAFLD obese group. In this cross-sectional study, elevated OS markers in obese adolescents with NAFLD were associated with insulin resistance. This data suggest that an antioxidant therapy might have a potential for treating NAFLD associated with insulin resistance.

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.

Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration.

PubMed

Patel, Y A; Gifford, E J; Glass, L M; McNeil, R; Turner, M J; Han, B; Provenzale, D; Choi, S S; Moylan, C A; Hunt, C M

2018-01-01

With its increasing incidence, nonalcoholic fatty liver disease (NAFLD) is of particular concern in the Veterans Health Administration (VHA). To evaluate risk factors for advanced fibrosis in biopsy-proven NAFLD in the VHA, to identify patients at risk for adverse outcomes. In randomly selected cases from VHA databases (2005-2015), we performed a retrospective case-control study in adults with biopsy-defined NAFLD or normal liver. Of 2091 patients reviewed, 399 met inclusion criteria. Normal controls (n = 65) had normal liver function. The four NAFLD cohorts included: NAFL steatosis (n = 76), nonalcoholic steatohepatitis (NASH) without fibrosis (n = 68), NAFLD/NASH stage 1-3 fibrosis (n = 82), and NAFLD/NASH cirrhosis (n = 70). NAFLD with hepatocellular carcinoma (HCC) was separately identified (n = 38). Most patients were older White men. NAFLD patients with any fibrosis were on average severely obese (BMI>35 kg/m 2 ). Diabetes (54.4%-79.6%) and hypertension (85.8%-100%) were more common in NAFLD with fibrosis or HCC. Across NAFLD, 12.3%-19.5% were enrolled in diet/exercise programs and 0%-2.6% had bariatric surgery. Hispanics exhibited higher rates of NASH (20.6%), while Blacks had low NAFLD rates (1.4%-11.8%), particularly NAFLD cirrhosis and HCC (1.4%-2.6%). Diabetes (OR 11.8, P < .001) and BMI (OR 1.4, P < .001) were the most significant predictors of advanced fibrosis. In the VHA, diabetes and severe obesity increased risk for advanced fibrosis in NAFLD. Of these patients, only a small proportion (~20%) had enrolled in diet/exercise programs or had bariatric surgery (~2%). These results suggest that providers should focus/tailor interventions to improve outcomes, particularly in those with diabetes and severe obesity. © 2017 John Wiley & Sons Ltd.

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

[The Development of Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease].

PubMed

Kwon, Oh Sang; Kim, Joon Hwan; Kim, Ju Hyun

2017-06-25

Non-alcoholic fatty liver disease (NAFLD) may be one of the important causes of cryptogenic hepatocellular carcinoma (HCC). NAFLD-related HCCs (NAFLD-HCCs) have the following clinical features: high body mass index, deranged lipid profiles, diabetes mellitus, hypertension, and metabolic syndrome. Among them, obesity, diabetes mellitus, and high Fe contents in the liver are risk factors of developing HCC in patients with NAFLD. Inflammatory cytokines, adipokines, insulin like growth factor-I, and lipotoxicity are intermingled and may cross react with each other to develop HCC. Because there is no guideline for early detection of HCC in patients with NAFLD, NAFLD-HCCs tend to be greater in size and in advanced stages when detected compared with hepatitis virus-related HCCs. Therefore, there is an urgent need of a surveillance program for the early detection of HCC. Treatment of NAFLD-HCCs is not different from other causes-related HCCs. However, patients with NAFLD-HCCs have cardiovascular disease and other metabolic problems, which may complicate treatment.

Endocrine causes of nonalcoholic fatty liver disease

PubMed Central

Marino, Laura; Jornayvaz, François R

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed. PMID:26494962

Influence of non-alcoholic fatty liver disease on the development of diabetes mellitus.

PubMed

Kasturiratne, Anuradhani; Weerasinghe, Sanjaya; Dassanayake, Anuradha S; Rajindrajith, Shaman; de Silva, Arjuna P; Kato, Norihiro; Wickremasinghe, A Rajitha; de Silva, H Janaka

2013-01-01

Non-alcoholic fatty liver disease (NAFLD) is linked to metabolic syndrome, and is known to be associated with impaired fasting glycemia and diabetes mellitus. This prospective community-based study was conducted to determine the association between NAFLD and incidence of diabetes mellitus in an urban adult population in Sri Lanka. Participants of the Ragama Health Study cohort were assessed for NAFLD using established ultrasound criteria in 2007. Those who were free of diabetes at baseline were followed up for 3 years. Incidence rates of diabetes mellitus were compared between subjects with and without NAFLD at baseline. Out of 2984 subjects, 926 had NAFLD and 676 had diabetes in 2007. Of the 2276 subjects who were free of diabetes in 2007, 1914 were re-assessed in 2010. After 3 years, 104 out of 528 subjects with NAFLD and 138 out of 1314 subjects without NAFLD had developed diabetes mellitus de novo. Incidence rates of diabetes were respectively 64.2 and 34 per 1000 person-years of follow up for those with and without NAFLD. NAFLD was an independent predictor of developing diabetes mellitus. Other independent predictors were impaired fasting glycemia and dyslipidemia. Subjects with ultrasonically diagnosed NAFLD have an increased risk of developing diabetes mellitus. Intervention for NAFLD through lifestyle modification may prevent progression of the current diabetes epidemic. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Professionals and interfamily violence against children and adolescents: in between legal and conceptual precepts.

PubMed

Schek, Gabriele; Silva, Mara Regina Santos da; Lacharité, Carl; Bueno, Maria Emilia Nunes

2016-01-01

To identify the conceptions of professionals regarding interfamily violence against children and adolescents. A qualitative study conducted with 15 professionals who had taken children and adolescents under their care as a result of interfamily violence. Data were collected between November, 2013, and March, 2015, through semi-structured interviews. Data were organized and analyzed using the Textual Discourse Analysis technique. The professional discourse highlighted that some legal aspects regarding the handling of interfamily violence against children and adolescents are neglected; an omission supported by the justification of professionals to preserve the family. We highlight the confrontation between the concept of family as a caregiver and the family that commits violence against children, in addition to the positioning of professionals, which does not include the family or the aggressor in the intervention process in facing situations of interfamily violence attended to by the services. Acting against interfamily violence requires professionals to do away with some pre-established concepts in ordee to put the actual needs of victims and families into evidence. Identificar, com base no discurso dos profissionais, suas concepções a respeito da violência intrafamiliar contra crianças e adolescentes. Estudo qualitativo, realizado com 15 profissionais, que tiveram sob seus cuidados crianças e adolescentes atendidas em decorrência da violência intrafamiliar. Os dados foram coletados entre novembro de 2013 e março de 2015, por meio de entrevistas semiestruturadas. Os dados foram organizados e analisados utilizando a técnica de Análise Textual Discursiva. O discurso dos profissionais colocou em evidência que alguns aspectos legais em relação ao manejo da violência intrafamiliar contra crianças e adolescentes são negligenciados, omissão respaldada pela justificativa dos profissionais de preservar a família. Destaca-se o confronto entre a concep

Variables Associated With Inpatient and Outpatient Resource Utilization Among Medicare Beneficiaries With Nonalcoholic Fatty Liver Disease With or Without Cirrhosis.

PubMed

Sayiner, Mehmet; Otgonsuren, Munkhzul; Cable, Rebecca; Younossi, Issah; Afendy, Mariam; Golabi, Pegah; Henry, Linda; Younossi, Zobair M

2017-03-01

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide with tremendous clinical burden. The economic burden of NAFLD is not well studied. To assess the economic burden of NAFLD. Medicare beneficiaries (January 1, 2010 to December 31, 2010) with NAFLD diagnosis by International Classification of Diseases, Ninth Revision codes in the absence of other liver diseases were selected. Inpatient and outpatient resource utilization parameters were total charges and total provider payments. NAFLD patients with compensated cirrhosis (CC) were compared with decompensated cirrhosis (DC). A total of 976 inpatients and 4742 outpatients with NAFLD were included-87% were white, 36% male, 30% had cardiovascular disease (CVD) or metabolic syndrome conditions, and 12% had cirrhosis. For inpatients, median total hospital charge was $36,289. NAFLD patients with cirrhosis had higher charges and payments than noncirrhotic NAFLD patients ($61,151 vs. $33,863 and $18,804 vs. $10,146, P<0.001). Compared with CC, NAFLD patients with DC had higher charges and payments (P<0.02). For outpatients, median total charge was $9,011. NAFLD patients with cirrhosis had higher charges and payments than noncirrhotic NAFLD patients ($12,049 vs. $8,830 and $2,586 vs. $1,734, P<0.001). Compared with CC, DC patients had higher total charges ($15,187 vs. $10,379, P=0.04). In multivariate analysis, variables associated with increased inpatient resource utilization were inpatient mortality, DC, and CVD; for outpatients, having CVD, obesity, and hypertension (all P<0.001). NAFLD is associated with significant economic burden to Medicare. Presence of cirrhosis and CVD are associated with increased resource utilization.

Variables Associated With Inpatient and Outpatient Resource Utilization Among Medicare Beneficiaries With Nonalcoholic Fatty Liver Disease With or Without Cirrhosis

PubMed Central

Sayiner, Mehmet; Otgonsuren, Munkhzul; Cable, Rebecca; Younossi, Issah; Afendy, Mariam; Golabi, Pegah; Henry, Linda

2017-01-01

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide with tremendous clinical burden. The economic burden of NAFLD is not well studied. Goal: To assess the economic burden of NAFLD. Study: Medicare beneficiaries (January 1, 2010 to December 31, 2010) with NAFLD diagnosis by International Classification of Diseases, Ninth Revision codes in the absence of other liver diseases were selected. Inpatient and outpatient resource utilization parameters were total charges and total provider payments. NAFLD patients with compensated cirrhosis (CC) were compared with decompensated cirrhosis (DC). Results: A total of 976 inpatients and 4742 outpatients with NAFLD were included—87% were white, 36% male, 30% had cardiovascular disease (CVD) or metabolic syndrome conditions, and 12% had cirrhosis. For inpatients, median total hospital charge was $36,289. NAFLD patients with cirrhosis had higher charges and payments than noncirrhotic NAFLD patients ($61,151 vs. $33,863 and $18,804 vs. $10,146, P<0.001). Compared with CC, NAFLD patients with DC had higher charges and payments (P<0.02). For outpatients, median total charge was $9,011. NAFLD patients with cirrhosis had higher charges and payments than noncirrhotic NAFLD patients ($12,049 vs. $8,830 and $2,586 vs. $1,734, P<0.001). Compared with CC, DC patients had higher total charges ($15,187 vs. $10,379, P=0.04). In multivariate analysis, variables associated with increased inpatient resource utilization were inpatient mortality, DC, and CVD; for outpatients, having CVD, obesity, and hypertension (all P<0.001). Conclusions: NAFLD is associated with significant economic burden to Medicare. Presence of cirrhosis and CVD are associated with increased resource utilization. PMID:27332747

Prevalence of Suspected Nonalcoholic Fatty Liver Disease In Lean Adolescents In The United States.

PubMed

Selvakumar, Praveen Kumar Conjeevaram; Kabbany, Mohammad Nasser; Lopez, Rocio; Rayas, Maria S; Lynch, Jane L; Alkhouri, Naim

2018-03-21

Nonalcoholic fatty liver disease (NAFLD) can develop in lean subjects referred to as lean NAFLD. We aim to evaluate the prevalence and risk factors of NAFLD in lean adolescents in the United States (US). Cross sectional data from 1482 lean subjects (body mass index < 85 percentile) aged between 12 and 18 years, who were enrolled in the National Health and Examination Survey during the 2005-2014 cycles were included. We defined suspected NAFLD as alanine aminotransferase > 25.8 U/L for boys and > 22.1 U/L for girls; hypertriglyceridemia as triglycerides ≥ 150 mg/dL; low HDL as HDL < 40 mg/dL and insulin resistance (IR) as homeostatic model assessment of IR ≥ 3. The mean weighted prevalence of suspected NAFLD among lean adolescents during 2005-2014 cycles was 8% (95% CI: 6.2, 9.9). Lean subjects with suspected NAFLD were significantly older compared to lean non-NAFLD subjects (15.5 vs. 15 years, p-value < 0.05). Low HDL (15.5% vs. 6.8%; p-value 0.016) and hypertriglyceridemia (10% vs. 3.9%; p-value 0.028) were also found to be more common among lean NAFLD subjects compared to their non-NAFLD counterparts. Presence of IR increased the risk of having suspected NAFLD by 4-fold among lean adolescents. Non-Hispanic black lean adolescents were less likely to have suspected NAFLD compared to non-Hispanic white lean adolescents. The estimated prevalence of suspected NAFLD among lean adolescents in the US was found to be 8% with evidence of metabolic derangements such as low HDL, hypertriglyceridemia and IR.

Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis?

PubMed

Mantovani, Alessandro; Gisondi, Paolo; Lonardo, Amedeo; Targher, Giovanni

2016-02-05

Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis.

Nonalcoholic fatty liver disease in Asia: emerging perspectives.

PubMed

Seto, Wai-Kay; Yuen, Man-Fung

2017-02-01

As in the West, nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease in Asia, with a prevalence higher than 40 % in some countries. The risk factors for NAFLD development are similar to those in Western countries, including increased body mass index, diabetes, insulin resistance, and metabolic syndrome. NAFLD in Asians is associated with different extrahepatic manifestations involving the cardiovascular, gastrointestinal, and renal systems. A considerable proportion of Asians with NAFLD are described as having "lean" NAFLD. Present in approximately 20 % of the Asian population, lean NAFLD is closely linked with insulin resistance, diabetes, and other metabolic complications, but its association with disease progression to nonalcoholic steatohepatitis and cirrhosis remains to be defined. There is emerging evidence of the interactions of NAFLD with hepatitis B virus and hepatitis C virus infection in Asia. Unlike in Western countries, NAFLD constitutes only a minority of cirrhosis and hepatocellular carcinoma cases in Asia. Possible explanations are the lower prevalence of obesity and the overwhelming problem of viral hepatitis in Asia. With aging of the obesity cohort in Asia, NAFLD-related liver complications are expected to increase.

Association of Blood Fatty Acid Composition and Dietary Pattern with the Risk of Non-Alcoholic Fatty Liver Disease in Patients Who Underwent Cholecystectomy.

PubMed

Shim, Poyoung; Choi, Dongho; Park, Yongsoon

2017-01-01

The relationship between diet and non-alcoholic fatty liver disease (NAFLD) in patients with gallstone disease and in those who have a high risk for NAFLD has not been investigated. This study was conducted to investigate the association between the risk of NAFLD and dietary pattern in patients who underwent cholecystectomy. Additionally, we assessed the association between erythrocyte fatty acid composition, a marker for diet, and the risk of NAFLD. Patients (n = 139) underwent liver ultrasonography to determine the presence of NAFLD before laparoscopic cholecystectomy, reported dietary intake using food frequency questionnaire, and were assessed for blood fatty acid composition. Fifty-eight patients were diagnosed with NAFLD. The risk of NAFLD was negatively associated with 2 dietary patterns: consuming whole grain and legumes and consuming fish, vegetables, and fruit. NAFLD was positively associated with the consumption of refined grain, meat, processed meat, and fried foods. Additionally, the risk of NAFLD was positively associated with erythrocyte levels of 16:0 and 18:2t, while it was negatively associated with 20:5n3, 22:5n3, and Omega-3 Index. The risk of NAFLD was negatively associated with a healthy dietary pattern of consuming whole grains, legumes, vegetables, fish, and fruit and with an erythrocyte level of n-3 polyunsaturated fatty acids rich in fish. © 2017 S. Karger AG, Basel.

Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease.

PubMed

Kumagai, Erina; Mano, Yohei; Yoshio, Sachiyo; Shoji, Hirotaka; Sugiyama, Masaya; Korenaga, Masaaki; Ishida, Tsuyoshi; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Kawaguchi, Takumi; Torimura, Takuji; Nozaki, Yuichi; Watanabe, Sumio; Mizokami, Masashi; Kanto, Tatsuya

2016-10-14

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. YKL-40, chitinase-like protein expressed in multiple tissues including liver, is involved in cell proliferation, inflammation and remodeling of the extracellular matrix. The aim of this study was to assess whether serum YKL-40 levels are associated with liver fibrosis in NAFLD patients. Serum YKL-40 levels were quantified in 111 NAFLD patients and 23 HCC patients with NAFLD. To identify the source of YKL-40, immunofluorescence staining of liver specimens from NAFLD patients was performed. Serum YKL-40 levels in NAFLD patients increased in accordance with the progression of liver fibrosis. Multivariate analysis revealed that YKL-40 was one of the independent factors significantly associated with severe fibrosis (F3-4). We established a new predictive model for fibrosis of NAFLD, using logistic regression analysis: YKL-40 based fibrosis score = -0.0545 + type IV collagen 7s * 0.3456 + YKL-40 * 0.0024. Serum YKL-40 levels of HCC patients with non-cirrhotic NAFLD were significantly higher than those without HCC. Immunofluorescence staining showed that YKL-40 was expressed by macrophages in liver tissue of NAFLD patients. In conclusion, macrophage-derived YKL-40 is a feasible biomarker of liver fibrosis in NAFLD patients.

Nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and its association with cardiovascular disease.

PubMed

Vanjiappan, Sivabal; Hamide, Abdoul; Ananthakrishnan, Ramesh; Periyasamy, Senthilkumar Gandhipuram; Mehalingam, Vadivelan

2018-01-31

Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver disease that ranges from hepatic steatosis to non-alcoholic steatohepatitis. Obesity and diabetes mellitus are the prime risk factors for NAFLD. The aim of this study was to find out the prevalence of NAFLD among patients with type 2 diabetes mellitus and to detect the association of NAFLD with cardiovascular disease in them. Prospective observational study. The study was conducted on 300 patients with type 2 diabetes mellitus attending the outpatient department of a tertiary care teaching hospital. All patients underwent hepatic ultrasonography to look for hepatic steatosis. Among the 300 patients, 124 were divided into NAFLD and non-NAFLD groups based on the ultrasound findings. These patients were subjected to electrocardiogram, 2D echocardiogram, carotid intima media thickness (CIMT) measurement and ankle brachial pressure index measurement along with measurement of markers of oxidative stress. Hepatic steatosis was present in 61% of diabetic patients in this study. Cardiovascular disease was not found to be significantly associated in diabetic patients with NAFLD. However, cardiovascular risk factors like CIMT, high sensitivity c-reactive protein (hs-CRP) and malondialdehyde (MDA) were elevated in these patients. hs-CRP and MDA levels were found to be significantly associated with the severity of NAFLD. There is a high prevalence of NAFLD in type 2 diabetic patients. No correlation was detected between the presence of NAFLD and cardiovascular disease in them; although there was an association between cardiovascular risk factors and NAFLD. Copyright © 2018. Published by Elsevier Ltd.

Knowledge, attitude and practice of the smear test and its relation with female age.

PubMed

Silveira, Nara Sibério Pinho; Vasconcelos, Camila Teixeira Moreira; Nicolau, Ana Izabel Oliveira; Oriá, Mônica Oliveira Batista; Pinheiro, Patricia Neyva da Costa; Pinheiro, Ana Karina Bezerra

2016-06-14

to verify the association among the knowledge attitude and practice of women in relation to the smear test and the age range. a cross-sectional research was undertaken, associated with the knowledge, attitude and practice survey at a Primary Health Care service. The sample consisted of 775 women, distributed in three age ranges: adolescent, young and elderly. although high rates of inappropriate knowledge were found in all age ranges, it was significantly higher among the adolescents (p=0.000). A similar trend was found in the attitude component, with percentages of inappropriateness in adolescence that drop as age advances (p=0.000). Nevertheless, no statistical difference among the groups was found in terms of practice (p=0.852). the study demonstrated a relation between the age range and knowledge, attitude and practice of the smear test. verificar a associação entre o conhecimento, atitude e prática de mulheres em relação ao exame colpocitológico e a faixa etária. trata-se de pesquisa de corte transversal associada ao inquérito conhecimento, atitude e prática, em uma Unidade de Atenção Primária à Saúde. A amostra foi composta por 775 mulheres, distribuídas em três faixas etárias: adolescentes, jovens e idosas. embora o conhecimento inadequado tenha tido altas taxas em todas as faixas etárias, foi significativamente superior entre as adolescentes (p=0,000). Tendência semelhante no componente atitude por apresentar percentuais de inadequabilidade na adolescência e decair com o avançar da idade (p=0,000). Todavia, não houve diferença estatística entre os grupos quanto à prática (p=0,852). o estudo demonstrou relação entre a faixa etária e o conhecimento, a atitude e a prática do exame colpocitológico. verificar la asociación entre el conocimiento, la actitud y práctica de mujeres con relación a la prueba colpocitológica y el rango de edad. se trata de investigación trasversal asociada a la encuesta conocimiento, actitud y pr

EMS Provider Perceptions on Termination of Resuscitation in a Large, Urban EMS System.

PubMed

Tataris, Katie L; Richards, Christopher T; Stein-Spencer, Leslee; Ryan, Stephanie; Lazzara, Pete; Weber, Joseph M

2017-01-01

Despite the value of out-of-hospital Termination of Resuscitation (TOR) and the scientific evidence in favor of this practice, TOR has not been uniformly adopted or consistently practiced in EMS systems. Previous focus group studies have identified multiple barriers to implementation of out of hospital TOR but existing literature on EMS provider perceptions is limited. We sought to identify EMS providers' perceived barriers to performing out-of-hospital TOR in a large urban EMS system. The Chicago EMS System is a regional collaborative of EMS physicians, nurses and provider agencies, including the Chicago Fire Department (CFD), which provides exclusive emergency response for 9-1-1 calls in Chicago. CFD is an urban, fire-based EMS agency with a tiered response, with fire-fighter EMTs and paramedics providing initial care, and single role paramedics providing supplemental care and transport. A 2-page written survey was distributed to understand providers' experiences with managing OHCA and perceived barriers to TOR to inform subsequent improvements in protocol development and education. Of 3500 EMS providers that received the survey, 2309 were completed (66%). Survey respondent demographics were fire-fighter/EMTB (69%), fire-fighter/paramedic (14%), and single role paramedic (17%). The most frequent barrier to field TOR was scene safety (86%). The most common safety issue identified was family reaction to TOR (68%) and many providers felt threatened by family when trying to perform TOR (38%). Providers with a higher career numbers of OHCA were more likely to have felt threatened by the family (OR 6.70, 95% CI 2.99-15.00) and single role paramedics were more likely than FF/EMTBs to have felt threatened (OR 3.34, 95% CI 2.65-4.22). Barriers to delivering a death notification after TOR, include being uncomfortable or threatened with possible family reaction (52%) and family asking to continue the resuscitation (45%). There was lack of formal prior death notification

Liver enzyme levels and hepatic iron content in Fatty liver: a noninvasive assessment in general population by T2* mapping.

PubMed

Radmard, Amir Reza; Poustchi, Hossein; Dadgostar, Mehrdad; Yoonessi, Ali; Kooraki, Soheil; Jafari, Elham; Hashemi Taheri, Amir Pejman; Malekzadeh, Reza; Merat, Shahin

2015-06-01

Existing evidence suggests potential contribution of iron in pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to investigate whether hepatic iron content correlates with liver enzyme levels in NAFLD using a noninvasive magnetic resonance imaging (MRI) technique. Subjects from Golestan Cohort Study were randomly selected. Diagnosis of NAFLD was made by combination of ultrasound and MRI. Subjects with NAFLD were divided into two groups with high (H-NAFLD) and low (L-NAFLD) enzyme level according to 95th percentile of alanine aminotransferase (ALT) value in normal population. Quantitative T2* maps of entire cross-sectional area of liver were calculated on pixel-by-pixel basis using a semiautomated software. A total of 207 subjects were enrolled. Mean T2* values were significantly lower in NAFLD group than controls (P < .001) indicating higher iron content. Male subjects with H-NAFLD had statistically lower T2* values than those with L-NAFLD in multivariate analysis (odds ratio, 0.74; 95% confidence interval [CI], 0.58-0.95), whereas this was not observed in women. Unlike women, there was significant negative correlation between ALT levels and T2* values in men with H-NAFLD (r = -0.66, P = .01). Every 1-millisecond decrement in T2* value was associated with 6.37 IU/L increase in ALT level (95% CI, 1.8-10.9, P = .01) in men with H-NAFLD. Higher hepatic iron in men with H-NAFLD, estimated by T2* mapping, may support the role of iron in possible progression of simple steatosis to nonalcoholic steatohepatitis. Lack of such correlation in women could be attributed to relatively lower iron storage or other mechanisms rather than iron. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

Is HOMA-IR a potential screening test for non-alcoholic fatty liver disease in adults with type 2 diabetes?

PubMed

Gutierrez-Buey, Gala; Núñez-Córdoba, Jorge M; Llavero-Valero, María; Gargallo, Javier; Salvador, Javier; Escalada, Javier

2017-06-01

Non-alcoholic fatty liver disease (NAFLD) is the commonest hepatic disease in many parts of the World, with particularly high prevalence in patients with type 2 diabetes (T2DM). However, a good screening test for NAFLD in T2DM has not been established. Insulin resistance (IR) has been associated with NAFLD, and homeostatic model assessment of insulin resistance (HOMA-IR), a good proxy for IR, may represent an affordable predictive test which could be easily applied in routine clinical practice. We aimed to evaluate the diagnostic accuracy of HOMA-IR for NAFLD in T2DM and sought to estimate an optimal cut-off value for discriminating NAFLD from non-NAFLD cases. We conducted a retrospective analysis of 56 well-controlled patients with T2DM (HbAc1<7%, on oral anti-diabetic and/or glucagon-like peptide-1 agonist treatment), who had at least one glucose and insulin level determined, and at least one hepatic imaging test (ultrasonography or computed tomography scanning). The prevalence of NAFLD was 73.2% (95% CI: 59.7-84.2) in our population. An association between HOMA-IR and NAFLD was found (OR 1.5; 95% CI: 1.03-2.1; p=0.033), independently of transaminases, fat percentage, BMI and triglyceride levels. The AUROC curve of HOMA-IR for identifying NAFLD was 80.7% (95% CI: 68.9-92.5). A value of HOMA-IR of 4.5 was estimated to be an optimal threshold for discriminating NAFLD from non-NAFLD cases. HOMA-IR is independently associated with the presence of NAFLD in adults with T2DM, and might potentially be applied in clinical practice as a screen for this condition. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome.

PubMed

Aguilar-Olivos, Nancy E; Almeda-Valdes, Paloma; Aguilar-Salinas, Carlos A; Uribe, Misael; Méndez-Sánchez, Nahum

2016-08-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD is strongly associated with obesity and metabolic syndrome (MetS). Current treatment of NAFLD is based on weight reduction. Bariatric surgery is the most effective treatment for morbid obesity and its associated metabolic comorbidities. There is evidence indicating that bariatric surgery improves histological and biochemical parameters of NAFLD, but currently is not considered a treatment option for NAFLD. The aim of this work is to review the evidence for the effects of bariatric surgery on NAFLD and the MetS. We found that insulin resistance, alterations in glucose metabolism, hypertension, plasma lipids, transaminases, liver steatosis, steatohepatitis and fibrosis improve after bariatric surgery. Weight loss and improvement of NAFLD are greater after RYGB than after other interventions. These findings were obtained from retrospective or cohort studies. There are no studies designed to evaluate liver-specific mortality, liver transplantation, or quality of life. Patients with indications for bariatric surgery will benefit from the improvements in the MetS and NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.

Nursing interventions in monitoring the adolescent with Cystic Fibrosis: a literature review.

PubMed

Reisinho, Maria da Conceição Marinho Sousa Ribeiro Oliveira; Gomes, Bárbara Pereira

2016-12-08

to search for nursing interventions focused on the improvement of quality of life and promotion of self-care of adolescents suffering from the Cystic Fibrosis. literature review. The inclusion criteria were: primary studies and studies with interventions developed by nurses in the adolescent population with Cystic Fibrosis, using Portuguese, Spanish, French and English with no time limit, and supported by the databases Scopus, Web of Science and CINAHL. The search expressions were: nursing AND care AND adolescent AND "Cystic Fibrosis" AND ("quality of life" OR "self-care"). a total of 59 articles was retrieved; 8 matched the criteria chosen. Nursing interventions targeted at adolescents with Cystic Fibrosis and their family members were identified. These interventions were organized according to the nurses' role, namely caregiver, coordinator, counsellor, researcher, trainer and care partner. nursing interventions targeted at following up the adolescent during the entire therapeutic process, involving the presence of parents/significant others, since both the adolescent and family have to be responsible for self-care. Healthcare professionals should be capable of identifying the specific needs of patients with chronic disease and their family, permitting a better understanding and adaptation to the health-disease transition process. buscar intervenções de enfermagem que enfoquem a melhoria da qualidade de vida e a promoção do autocuidado em adolescentes que sofrem de fibrose cística. revisão de literatura. Os critérios de inclusão foram: estudos primários e estudos com intervenções desenvolvidas por enfermeiros na população adolescente com fibrose cística, em português, espanhol, francês e inglês, sem delimitação temporal, nas bases de dados Scopus, Web of Science e CINAHL. Os termos utilizados na busca foram: enfermagem AND cuidado AND adolescente AND "Fibrose Cística" AND ("qualidade de vida" OR "autocuidado"). ao total, 59 artigos foram

Coffee consumption is not associated with prevalent subclinical cardiovascular disease (CVD) or the risk of CVD events, in nonalcoholic fatty liver disease: results from the multi-ethnic study of atherosclerosis.

PubMed

Simon, Tracey G; Trejo, Maria Esther Perez; Zeb, Irfan; Frazier-Wood, Alexis C; McClelland, Robyn L; Chung, Raymond T; Budoff, Matthew J

2017-10-01

Atherosclerosis and its clinical sequelae represent the leading cause of mortality among patients with nonalcoholic fatty liver disease (NAFLD). While epidemiologic data support the hepatoprotective benefits of coffee in NAFLD, whether coffee improves NAFLD-associated CVD risk is unknown. We examined 3710 ethnically-diverse participants from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, without history of known liver disease, and with available coffee data from a validated 120-item food frequency questionnaire. All participants underwent baseline non-contrast cardiac CT from which NAFLD was defined by liver:spleen ratio (L:S<1.0), and subclinical CVD was defined by coronary artery calcium (CAC)>0. Major CVD events were defined by the first occurrence of myocardial infarction, cardiac arrest, angina, stroke, or CVD death. We used log-binomial regression to calculate the adjusted prevalence ratio (PR) for CAC>0 by coffee intake and NAFLD status, and events were compared between groups using frequency of events within adjusted Cox proportional hazard regression models. Seventeen percent (N=637) of participants met criteria for NAFLD. NAFLD participants were more likely to have elevated BMI (mean 31.1±5.5kg/m 2 vs. 28.0±5.2kg/m 2 , p<0.0001), and diabetes (22% vs. 11%, p<0.0001), but did not differ in daily coffee consumption (p=0.97). Among NAFLD participants, coffee consumption was not associated with prevalent, baseline CAC>0 (PR=1.02 [0.98-1.07]). Over 12.8years of follow-up, 93 NAFLD and 415 non-NAFLD participants experienced a CV event. However, coffee intake was not associated with incident CVD events, in either NAFLD (HR=1.05 [0.91-1.21]) or non-NAFLD participants (HR=1.03 [0.97-1.11]). In a large, population-based cohort, coffee consumption was not associated with the prevalence of subclinical CVD, nor did coffee impact the future risk of major CVD events, regardless of underlying NAFLD status. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus.

PubMed

Targher, Giovanni; Lonardo, Amedeo; Byrne, Christopher D

2018-02-01

Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 70-80% of patients with type 2 diabetes mellitus and up to 30-40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases.

Biochemical Profile of Nonalcoholic Fatty Liver Disease Patients in Eastern India with Histopathological Correlation.

PubMed

Swain, Manorama; Nath, Preetam; Parida, Prasant Kumar; Narayan, Jimmy; Padhi, Pradeep Kumar; Pati, Girish Kumar; Singh, Ayaskanta; Misra, Bijay; Misra, Debasis; Kar, Sanjib Kumar; Panigrahi, Manas Kumar; Meher, Chudamani; Agrawal, Omprakash; Rout, Niranjan; Pattnaik, Kaumudee; Bhuyan, Pallavi; Mishra, Pramila Kumari; Singh, Shivaram Prasad

2017-07-01

Aminotransferase assay is often used as a screening test as well as an endpoint for resolution of disease in nonalcoholic fatty liver disease (NAFLD). Aim of the study was to evaluate the relationship of transaminase level with metabolic variables and histology in NAFLD. Single center observational study was conducted in a gastroenterology clinic at Cuttack in coastal Odisha. Subjects were consecutive patients presenting with functional bowel disease and undergoing abdominal sonography. All participants were evaluated for the presence of metabolic syndrome (MS), insulin resistance, liver function test and lipid profile. Various parameters were compared between NAFLD subjects and controls. 53.5 % of NAFLD had normal serum transaminases, whereas 20.8 % of healthy controls had transaminitis. NAFLD patients had significantly higher BMI, fasting plasma glucose, serum transaminases, serum triglycerides, serum insulin and homeostatic model assessment (HOMA) IR than controls. NAFLD patients who had transaminitis had significantly higher incidence of MS and higher mean HOMA IR than those without. There was no significant difference in histopathological features between NAFLD with and without transaminitis. To conclude, over half of NAFLD subjects do not have transaminitis while transaminitis is present in a fifth of healthy people without fatty liver. Hence serum transaminase should not be used as screening test for NAFLD. NAFLD patients with transaminitis had a higher incidence of MS and insulin resistance than those without. However, there was no significant difference in histopathological features between these two groups.

Non-alcoholic fatty liver disease and diabetes: From physiopathological interplay to diagnosis and treatment

PubMed Central

Leite, Nathalie C; Villela-Nogueira, Cristiane A; Cardoso, Claudia R L; Salles, Gil F

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2 diabetes are at a particularly high risk for developing the progressive forms of NAFLD, non-alcoholic steatohepatitis and associated advanced liver fibrosis. Moreover, diabetes is an independent risk factor for NAFLD progression, and for hepatocellular carcinoma development and liver-related mortality in prospective studies. Notwithstanding, patients with NAFLD have an elevated prevalence of prediabetes. Recent studies have shown that NAFLD presence predicts the development of type 2 diabetes. Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients. The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods, although histopathological evaluation is still considered the gold standard diagnostic method. An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking. We sought to outline the published data including epidemiology, pathogenesis, diagnosis and treatment of NAFLD in diabetic patients, in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus. PMID:25024596

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.

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.

Non-alcoholic Fatty Liver Disease and Metabolic Syndrome-Position Paper of the Indian National Association for the Study of the Liver, Endocrine Society of India, Indian College of Cardiology and Indian Society of Gastroenterology.

PubMed

Duseja, Ajay; Singh, Shivaram P; Saraswat, Vivek A; Acharya, Subrat K; Chawla, Yogesh K; Chowdhury, Subhankar; Dhiman, Radha K; Jayakumar, Rohinivilasam V; Madan, Kaushal; Misra, Sri P; Mishra, Hrudananda; Modi, Sunil K; Muruganathan, Arumugam; Saboo, Banshi; Sahay, Rakesh; Upadhyay, Rajesh

2015-03-01

Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome. Prevalence of metabolic risk factors including diabetes mellitus, obesity, etc. is rapidly increasing in India putting this population at risk for NAFLD. Patients with NAFLD are at increased risk for liver-related morbidity and mortality and also cardiovascular disease risk and increased incidence of diabetes mellitus on long-term follow-up. Management of patients with NAFLD may require a multi-disciplinary approach involving not only the hepatologists but also the internists, cardiologists, and endocrinologists. This position paper which is a combined effort of the Indian National Association for Study of the Liver (INASL), Endocrine Society of India (ESI), Indian College of Cardiology (ICC) and the Indian Society of Gastroenterology (ISG) defines the spectrum of NAFLD and the association of NAFLD with insulin resistance and metabolic syndrome besides suggesting preferred approaches for the diagnosis and management of patients with NAFLD in the Indian context.

Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: An update

PubMed Central

Athyros, Vasilios G; Tziomalos, Konstantinos; Katsiki, Niki; Doumas, Michael; Karagiannis, Asterios; Mikhailidis, Dimitri P

2015-01-01

Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above. PMID:26078558

Non-alcoholic Fatty Liver Disease and Metabolic Syndrome—Position Paper of the Indian National Association for the Study of the Liver, Endocrine Society of India, Indian College of Cardiology and Indian Society of Gastroenterology

PubMed Central

Duseja, Ajay; Singh, Shivaram P.; Saraswat, Vivek A.; Acharya, Subrat K.; Chawla, Yogesh K.; Chowdhury, Subhankar; Dhiman, Radha K.; Jayakumar, Rohinivilasam V.; Madan, Kaushal; Misra, Sri P.; Mishra, Hrudananda; Modi, Sunil K.; Muruganathan, Arumugam; Saboo, Banshi; Sahay, Rakesh; Upadhyay, Rajesh

2015-01-01

Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome. Prevalence of metabolic risk factors including diabetes mellitus, obesity, etc. is rapidly increasing in India putting this population at risk for NAFLD. Patients with NAFLD are at increased risk for liver-related morbidity and mortality and also cardiovascular disease risk and increased incidence of diabetes mellitus on long-term follow-up. Management of patients with NAFLD may require a multi-disciplinary approach involving not only the hepatologists but also the internists, cardiologists, and endocrinologists. This position paper which is a combined effort of the Indian National Association for Study of the Liver (INASL), Endocrine Society of India (ESI), Indian College of Cardiology (ICC) and the Indian Society of Gastroenterology (ISG) defines the spectrum of NAFLD and the association of NAFLD with insulin resistance and metabolic syndrome besides suggesting preferred approaches for the diagnosis and management of patients with NAFLD in the Indian context. PMID:25941433

Comparison of the Phenotype and Approach to Pediatric Versus Adult Patients with Nonalcoholic Fatty Liver Disease

PubMed Central

Nobili, V; Alisi, A; Newton, Kimberly P.; Schwimmer, Jeffrey B.

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is one of the main chronic non-communicable diseases in westernized societies; its worldwide prevalence has doubled during the last 20 years. NAFLD has serious health implications not only for adults, but also for children. However, pediatric NAFLD is not only an important global problem in itself, but it is likely to be associated with increases in comorbidities such as metabolic syndrome and cardiovascular diseases. There are several differences between NAFLD in children and adults and it is not clear whether the disease observed in children is the initial phase of a process that progresses with age. The increasing prevalence of pediatric NAFLD has serious implications for the future adult population requiring appropriate action. Studies of NAFLD progression, pathogenesis, and management should evaluate disease phenotypes in children and follow these over patient lifetimes. We review the similarities and differences of NAFLD between children and adults. PMID:27003600

Hypogonadism and non-alcoholic fatty liver disease.

PubMed

Mintziori, Gesthimani; Poulakos, Pavlos; Tsametis, Christos; Goulis, Dimitrios G

2017-06-01

Non-alcoholic fatty liver disease (NAFLD) is more common in men than in women. Thus, it has been suggested that sex steroids do have a role in the development of NAFLD. The aim of the current paper is to illustrate the association between NAFLD and hypogonadism, by reviewing data derived from both human and animal studies. The prevalence of NAFLD is high in men with hypogonadism, including those with idiopathic hypogonadotropic hypogonadism (IHH), as well as in women in post-menopause, those under estrogen receptor antagonist treatment or women with Turner syndrome. Estrogens seem to play a pivotal role in hepatic lipid homeostasis, as demonstrated in animal models with diminished ovarian estrogens (i.e., ovariectomized mice) and low serum testosterone (T) concentration is independently associated with NAFLD. The elucidation of the exact role of sex steroids in NAFLD pathogenesis would create a unique opportunity to develop novel therapies to tackle NAFLD disease.

NASH in Nondiabetic Endocrine Disorders.

PubMed

Wang, Timothy; Yang, Wei; Karakas, Sidika; Sarkar, Souvik

2018-06-06

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease, including hepatic steatosis, inflammation, and fibrosis. NAFLD carries the risk of progression to cirrhosis with its associated complications and hepatocellular carcinoma. It is now the most common liver disease in the Western world and its prevalence is increasing. While the association between NAFLD and type 2 diabetes has been well documented, there is significantly less understanding of the pathophysiology and progression of NAFLD in patients with other endocrine disorders affecting metabolism in various ways. Some of the more common endocrine disorders such as polycystic ovarian syndrome, growth hormone deficiency, hypothyroidism, and hypogonadism are known in clinical practice to be associated with NAFLD. Medications that alter the endocrine system such as tamoxifen and adrenal steroids have also been attributed to significant NAFLD. The key to management of NAFLD at this time are dietary changes and exercise to achieve weight loss. Unfortunately, a large proportion of the patients with these endocrine disorders are unable to achieve either. This review aims to examine and summarize the current published literature that have evaluated the association between NAFLD and the above endocrine disorders and potential therapeutic interventions in each case.

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.

Nonalcoholic fatty liver disease severity is associated with the ratios of total cholesterol and triglycerides to high-density lipoprotein cholesterol.

PubMed

Wu, Kuan-Ta; Kuo, Po-Lin; Su, Shih-Bin; Chen, Yi-Yu; Yeh, Ming-Lum; Huang, Ching-I; Yang, Jeng-Fu; Lin, Chia-I; Hsieh, Meng-Hsuan; Hsieh, Ming-Yen; Huang, Chung-Feng; Lin, Wen-Yi; Yu, Ming-Lung; Dai, Chia-Yen; Wang, Hsien-Yi

2016-01-01

Limited data support the notion that lipid ratios are risk factors for nonalcoholic fatty liver disease (NAFLD). We evaluated the association between lipid ratios and NAFLD. This was a large population, cross-sectional, retrospective study. Data on NAFLD severity, blood pressure, fasting glucose, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels were obtained from 44,767 examinees at single health checkup center. The enrollees were stratified into four subgroups based on their TC/HDL-C and TG/HDL-C ratios. We used multivariate analyses to evaluate the odds between lipid ratios and NAFLD. The prevalence rate of fatty liver in this study was 53.76%. In the baseline subgroup with the lowest TC/HDL-C and TG/HDL-C ratios, the prevalence of NAFLD, hypertension, and diabetes was lower than that of the other three subgroups. Patients with higher lipid ratios had a significantly greater risk for advanced NAFLD. Adults with high TC/HDL-C or TG/HDL-C ratios, or both, have a greater risk for NAFLD, especially advanced NAFLD. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

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.

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

Association between bilirubin and risk of Non-Alcoholic Fatty Liver Disease based on a prospective cohort study.

PubMed

Tian, Jianbo; Zhong, Rong; Liu, Cheng; Tang, Yuhan; Gong, Jing; Chang, Jiang; Lou, Jiao; Ke, Juntao; Li, Jiaoyuan; Zhang, Yi; Yang, Yang; Zhu, Ying; Gong, Yajie; Xu, Yanyan; Liu, Peiyi; Yu, Xiao; Xiao, Lin; Du, Min; Yang, Ling; Yuan, Jing; Wang, Youjie; Chen, Weihong; Wei, Sheng; Liang, Yuan; Zhang, Xiaomin; He, Meian; Wu, Tangchun; Yao, Ping; Miao, Xiaoping

2016-08-03

The study aimed to assess the association between total, direct, and indirect bilirubin and nonalcoholic fatty live disease (NAFLD) risk given its high prevalence and serious clinical prognosis. Among 27,009 subjects who participated in a healthy screening program from the Dongfeng-Tongji cohort study in 2008, 8189 eligible subjects (aged 35-86 years; males, 43.95%) were ultimately enrolled. The incidence rates of NAFLD in 2013 were compared with respect to baseline bilirubin levels among subjects free of NAFLD, and the effect sizes were estimated by logistic regression analysis. During 5 years follow-up, we observed 1956 cases of newly developed NAFLD with the overall incidence of 23.88%. Direct bilirubin was presented to inversely associate with NAFLD risk. Compared with quartile 1 of direct bilirubin, the multivariable-adjusted ORs (95% CIs) for NAFLD of quartile 2 to 4 were 1.104 (0.867-1.187), 0.843 (0.719-0.989), and 0.768 (0.652-0.905), respectively, P for trend 0.002). Similarly, inverse effects of direct bilirubin on NAFLD incidence were also observed when stratified by sex and BMI. However, no significant associations were found between total, and indirect bilirubin and NAFLD risk. Direct bilirubin reduced NAFLD risk independent of possible confounders among middle-aged and elderly Chinese population, probably based on the endogenous antioxidation of bilirubin.

Nonalcoholic fatty liver disease is associated with atherosclerosis in middle-aged and elderly Chinese.

PubMed

Huang, Yun; Bi, Yufang; Xu, Min; Ma, Zhimin; Xu, Yu; Wang, Tiange; Li, Mian; Liu, Yu; Lu, Jieli; Chen, Yuhong; Huang, Fei; Xu, Baihui; Zhang, Jie; Wang, Weiqing; Li, Xiaoying; Ning, Guang

2012-09-01

To evaluate the associations between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis. A total of 8632 participants aged ≥ 40 years from Jiading district, Shanghai, were included in the present study. The presence of NAFLD was evaluated by ultrasonography. Carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) were measured in each participant. The prevalence of NAFLD was 30.0% in the total population, with 30.3% in men and 29.9% in women, respectively. Subjects with NAFLD had remarkably higher CIMT and ba-PWV compared with those without NAFLD (0.594 ± 0.105 mm versus 0.578±0.109 mm, P<0.0001; 1665 ± 424 cm/s versus 1558 ± 430 cm/s, P<0.0001). Subjects with both NAFLD and metabolic syndrome had significantly higher CIMT and ba-PWV compared with those with neither or either of these 2 diseases after adjustment for age and sex (all P<0.05). Logistic regressions also revealed that NAFLD conferred 35% and 30% increased odds ratios of elevated CIMT and ba-PWV, independent of conventional risk factors and the presence of metabolic syndrome. NAFLD was associated with elevated CIMT and ba-PWV, independent of conventional cardiovascular disease risk factors and metabolic syndrome. The effects of NAFLD and metabolic syndrome on atherosclerosis might not fully overlap.

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

Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease.

PubMed

Wieland, A; Frank, D N; Harnke, B; Bambha, K

2015-11-01

The human intestinal microbiota is a key regulator of host metabolic and immune functions and alterations in the microbiome ('dysbiosis') have been implicated in several human diseases. Because of the anatomical links between the intestines and the liver, dysbiosis may also disrupt hepatic function and thereby contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). To perform a comprehensive review of the medical literature investigating associations between intestinal dysbiosis and NAFLD, with a particular emphasis on studies that characterise the microbiome in NAFLD. We conducted a search of PubMed, Embase, and Web of Science using multiple search terms including: 'NAFLD, NASH, fatty liver, steatohepatitis' combined with 'metagenome, microbiom*, microbiota*, fecal flora, intestinal flora, gut bacteria'. Results were manually reviewed and studies selected based on relevance to intestinal microbiota and NAFLD. We also included studies that addressed potential mechanistic models of pathways linking the dysbiosis to NAFLD. Nine studies (five human and four animal models) were identified in our search that assessed associations between specific intestinal microbiota composition and NAFLD. We reviewed and summarised the results of additional investigations that more broadly addressed the mechanisms by which the microbiome may impact NAFLD pathogenesis. Investigations in humans and animals demonstrate associations between intestinal dysbiosis and NAFLD; however, causality has not been proven and mechanistic links require further delineation. As the field of microbiome research matures in techniques and study design, more detailed insights into NAFLD pathogenesis and its associations with the intestinal microbiota will be elucidated. © 2015 John Wiley & Sons Ltd.

Possible association between Helicobacter pylori infection and nonalcoholic fatty liver disease.

PubMed

Chen, Chang-Xi; Mao, Yu-Shan; Foster, Parker; Zhu, Zhong-Wei; Du, Juan; Guo, Chuan-Yong

2017-03-01

Possible association between Helicobacter pylori infection (HPI) and nonalcoholic fatty liver disease (NAFLD) has been proposed by several studies with inconsistent conclusions. Here, we studied the association between HPI and NAFLD at 3 levels: (i) genetic level; (ii) small molecular level; and (iii) clinical level. Relation data between diseases, genes, and small molecules were acquired from Pathway Studio ResNet Mammalian database. Clinical data were acquired from 2263 elderly South Chinese subjects, including 603 NAFLD patients and 1660 subjects without NAFLD. Results showed that HPI and NAFLD present significantly shared genetic bases (95 genes, p value = 2.5E-72), demonstrating multiple common genetic pathways (enrichment p value ≤ 4.38E-20 for the top 10 pathways). Genetic network analysis suggested that mutual regulation may exist between HPI and NAFLD through 21 out of 95 genes. Furthermore, 85 out of the 95 genes manifested strong interaction with 12 small molecules/drugs that demonstrate effectiveness in treating both diseases. Clinical results showed that HPI rate in the NAFLD group was significantly higher than that in the group without NAFLD (51.9% vs. 43.6%; p value = 4.9E-4). Multivariate logistic regression results supported the observations and suggested that HPI served as a risk factor for NAFLD in the experiment data studied (odds ratio: 1.387, p value = 0.018). Results from this study support the hypothesis that complex biological association may exist between HPI and NAFLD, which partially explains the significant clinical co-incidence in the elderly population of south China.

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

PubMed Central

Perumpail, Brandon J; Khan, Muhammad Ali; Yoo, Eric R; Cholankeril, George; Kim, Donghee; Ahmed, Aijaz

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis. PMID:29307986

Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension.

PubMed

Fallo, F; Dalla Pozza, A; Sonino, N; Lupia, M; Tona, F; Federspil, G; Ermani, M; Catena, C; Soardo, G; Di Piazza, L; Bernardi, S; Bertolotto, M; Pinamonti, B; Fabris, B; Sechi, L A

2009-11-01

Insulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography. The two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P < 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis. Non-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.

Serum phospholipid omega-3 polyunsaturated fatty acids and insulin resistance in type 2 diabetes mellitus and non-alcoholic fatty liver disease.

PubMed

Lou, Da-Jun; Zhu, Qi-Qian; Si, Xu-Wei; Guan, Li-Li; You, Qiao-Ying; Yu, Zhong-Ming; Zhang, Ai-Zhen

2014-01-01

To investigate the relationship between serum phospholipid omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). 51 patients with T2DM and NAFLD (T2DM+NAFLD group), 50 with T2DM alone (T2DM group), 45 with NAFLD alone (NAFLD group), and 42 healthy control subjects (NC group) were studied. Serum ω-3 PUFA profiles were analyzed by gas chromatography, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and serum lipid concentrations were measured. Insulin resistance was assessed by the homeostasis model assessment method (HOMA-IR). HOMA-IR levels were higher in the T2DM+NAFLD group than in the T2DM, NAFLD and NC groups (p<0.05), as were ALT, AST, GGT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) concentrations (p<0.05). Conversely, serum ω-3 PUFA levels were significantly lower in the T2DM+NAFLD group than in the other groups (p<0.05). The ω-3 PUFA level was negatively correlated with HOMA-IR, TC, LDL-C and TG. Serum phospholipid ω-3 PUFA levels were significantly decreased in patients with T2DM and NAFLD, and were negatively related with insulin resistance. Thus, reduced ω-3 PUFAs may play an important role in the development of T2DM and NAFLD. Copyright © 2014 Elsevier Inc. All rights reserved.

Obstructive sleep apnea is an important predictor of hepatic fibrosis in patients with nonalcoholic fatty liver disease in a tertiary care center.

PubMed

Agrawal, Swastik; Duseja, Ajay; Aggarwal, Ashutosh; Das, Ashim; Mehta, Manu; Dhiman, Radha K; Chawla, Yogesh

2015-04-01

The association of obstructive sleep apnea (OSA) with nonalcoholic fatty liver disease (NAFLD) has only been studied in selected subgroups such as the morbidly obese. We aimed to determine the prevalence and effect of OSA on NAFLD and vice versa in unselected patients attending the outpatient department. OSA was diagnosed by polysomnography, done in patients having symptoms of OSA, in patients with NAFLD attending the liver clinic. Polysomnography-proven patients with OSA attending the chest clinic were evaluated for NAFLD by ultrasonography. Anthropometry, liver function tests, metabolic syndrome evaluation and transient elastography were performed in all patients. Three (3%; 95% CI 1.03-8.45%) out of 100 patients with NAFLD (mean age 41 ± 11 years) had symptomatic OSA. Of 23 patients with OSA (mean age 46 ± 12 years,), 3 (13%) had mild, 5 (22%) moderate and 15 (65%) severe OSA. Twenty-one (91.3%; 95% CI 73.2-97.6%) patients with OSA had NAFLD, while raised hepatic transaminase levels were seen in seven (30.4%; 95% CI 15.6-50.9%). Body mass index (OR 1.21, 95% CI 1.02-1.44) and male gender (OR 4.79, 95% CI 1.12-20.48) were significant independent predictors of OSA in NAFLD. The apnea-hypopnea index (OR 1.084, 95% CI 1.002-1.172), a marker of OSA severity, was the only significant independent predictor of significant fibrosis in patients with NAFLD. Prevalence of symptomatic OSA in patients with NAFLD is low and is predicted by male gender and obesity. Prevalence of NAFLD in patients with OSA is very high. Significant hepatic fibrosis in patients with NAFLD is predicted by OSA independent of obesity and metabolic syndrome.

Racial and Ethnic Disparities in Nonalcoholic Fatty Liver Disease Prevalence, Severity, and Outcomes in the United States: A Systematic Review and Meta-analysis.

PubMed

Rich, Nicole E; Oji, Stefany; Mufti, Arjmand R; Browning, Jeffrey D; Parikh, Neehar D; Odewole, Mobolaji; Mayo, Helen; Singal, Amit G

2018-02-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting 75-100 million Americans. However, the disease burden may not be equally distributed among races or ethnicities. We conducted a systematic review and meta-analysis to characterize racial and ethnic disparities in NAFLD prevalence, severity, and prognosis. We searched MEDLINE, EMBASE, and Cochrane databases through August 2016 for studies that reported NAFLD prevalence in population-based or high-risk cohorts, NAFLD severity including presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis, and NAFLD prognosis including development of cirrhosis complications and mortality. Pooled relative risks, according to race and ethnicity, were calculated for each outcome using the DerSimonian and Laird method for a random-effects model. We identified 34 studies comprising 368,569 unique patients that characterized disparities in NAFLD prevalence, severity, or prognosis. NAFLD prevalence was highest in Hispanics, intermediate in Whites, and lowest in Blacks, although differences between groups were smaller in high-risk cohorts (range 47.6%-55.5%) than population-based cohorts (range, 13.0%-22.9%). Among patients with NAFLD, risk of NASH was higher in Hispanics (relative risk, 1.09; 95% CI, 0.98-1.21) and lower in Blacks (relative risk, 0.72; 95% CI, 0.60-0.87) than Whites. However, the proportion of patients with significant fibrosis did not significantly differ among racial or ethnic groups. Data were limited and discordant on racial or ethnic disparities in outcomes of patients with NAFLD. In a systematic review and meta-analysis, we found significant racial and ethnic disparities in NAFLD prevalence and severity in the United States, with the highest burden in Hispanics and lowest burden in Blacks. However, data are discordant on racial or ethnic differences in outcomes of patients with NAFLD. Copyright © 2018 AGA Institute. Published by

Relationship between Hypothyroidism and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

PubMed

He, Weiwei; An, Xiaofei; Li, Ling; Shao, Xiaoqing; Li, Qian; Yao, Qiuming; Zhang, Jin-An

2017-01-01

Previous studies propose that hypothyroidism might play a crucial role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), but findings from published studies on the relationship between hypothyroidism and NAFLD are still controversial. Our study aimed to make a comprehensive evaluation of the relationship between hypothyroidism and NAFLD through a meta-analysis. PubMed, China Dissertation Database, and EMBASE databases were searched to find observational studies assessing the relationship between hypothyroidism and NAFLD. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to evaluate the strength of the relationship between hypothyroidism and NAFLD through meta-analysis. Thirteen articles were ultimately included in our meta-analysis. Meta-analysis of the 13 studies found a high correlation between hypothyroidism and NAFLD (OR = 1.52, 95% CI 1.24-1.87, P  < 0.001). Meta-analysis of 9 studies providing adjusted ORs found that hypothyroidism was independently correlated with NAFLD (OR = 1.72, 95% CI 1.32-2.23, P  < 0.001). Subgroup analysis found that both overt hypothyroidism and subclinical hypothyroidism were significantly correlated with NAFLD, and the pooled ORs were 1.70 (95% CI 1.23-2.36, P  = 0.002) and 1.40 (95% CI 1.10-1.77, P  = 0.006), respectively. Besides, meta-analysis of studies providing adjusted ORs also found that both overt hypothyroidism and subclinical hypothyroidism were independently correlated with NAFLD, and the pooled ORs were 1.81 (95% CI 1.30-2.52, P  < 0.001) and 1.63 (95% CI 1.19-2.24, P  = 0.002), respectively. The meta-analysis provides strong epidemiological evidence for the relationship between hypothyroidism and NAFLD. Both individuals with subclinical and overt hypothyroidism are at higher risk for NAFLD than euthyroid subjects.

Short-term aerobic exercise training improves gut peptide regulation in nonalcoholic fatty liver disease.

PubMed

Kullman, Emily L; Kelly, Karen R; Haus, Jacob M; Fealy, Ciaran E; Scelsi, Amanda R; Pagadala, Mangesh R; Flask, Chris A; McCullough, Arthur J; Kirwan, John P

2016-05-15

Obesity-related nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease. Exercise and diet are uniformly prescribed treatments for NAFLD; however, there are limited empirical data on the effects of exercise training on metabolic function in these patients. The purpose of this study was to investigate the fasting and glucose-stimulated adaptation of gut peptides to short-term aerobic exercise training in patients with NAFLD. Twenty-two obese subjects, 16 with NAFLD [body mass index (BMI), 33.2 ± 1.1 (SE) kg/m(2)] and 6 obese controls (BMI, 31.3 ± 1.2 kg/m(2)), were enrolled in a supervised aerobic exercise program (60 min/day, 85% of their heart rate maximum, for 7 days). Fasting and glucose-stimulated glucagon-like peptide-1 (GLP-17-36) and peptide tyrosine tyrosine (PYYTotal) concentrations in plasma were assessed before and after the exercise program. Initially, the NAFLD group had higher fasting PYY (NAFLD = 117 ± 18.6, control = 47.2 ± 6.4 pg/ml, P < 0.05) and GLP-1 (NAFLD = 12.4 ± 2.2, control = 6.2 ± 0.2 pg/ml, P < 0.05) and did not significantly increase GLP-1 or PYY in response to glucose ingestion. After the exercise program, fasting GLP-1 was reduced in the NAFLD group (10.7 ± 2.0 pg/ml, P < 0.05). Furthermore, exercise training led to significant increase in the acute (0-30 min) PYY and GLP-1 responses to glucose in the NAFLD group, while the total area under the glucose-stimulated GLP-1 response curve was reduced in both NAFLD and controls (P < 0.05). In summary, 7 days of vigorous aerobic exercise normalized the dynamic PYY and GLP-1 responses to nutrient stimulation and reduced the GLP-1 response in NAFLD, suggesting that exercise positively modulates gut hormone regulation in obese adults with NAFLD. Copyright © 2016 the American Physiological Society.

Free triiodothyronine levels are positively associated with non-alcoholic fatty liver disease in euthyroid middle-aged subjects.

PubMed

Liu, Guoli; Zheng, Xiao; Guan, Liying; Jiang, Zhi; Lin, Haiyan; Jiang, Qiang; Zhang, Nan; Zhang, Yikun; Zhang, Xu; Yu, Chunxiao; Guan, Qingbo

2015-01-01

Studies on the relationship between thyroid function and non-alcoholic fatty liver disease (NAFLD) among euthyroid subjects have produced conflicting results. The aim of this study was to investigate the association between thyroid function and the presence of NAFLD in a large-sample middle-aged euthyroid subjects. A total of 2576 euthyroid subjects who underwent health check-up were included. NAFLD was diagnosed by hepatic ultrasonography. Conventional risk factors for NAFLD were assessed as well as serum levels of TSH, FT3 and FT4. Levels of FT3 were significantly higher in NAFLD group (5.12 ± 0.58 versus 4.84 ± 0.58 pmol/L, adjusted p = 0.000) than non-NAFLD group, while levels of TSH and FT4 were comparable between NAFLD and non-NAFLD groups (TSH: 2.13 ± 0.90 versus 2.20 ± 0.93 mIU/L, adjusted p = 0.190; FT4: 16.41 ± 2.04 versus 16.18 ± 2.06 pmol/L, adjusted p = 0.146, respectively). Levels of FT3 were positively correlated with components of metabolic syndrome. Multivariate logistic regression analysis revealed that high level of FT3 was an independent predictor for NAFLD (odds ratio: 1.253, p = 0.040). The relationship between FT4 and NAFLD in women was different according to menopausal status, with negative association in pre-menopausal women (OR: 0.777, 95% CI: 0.617-0.979, p = 0.032) and null association in post-menopausal women (OR: 1.037, 95% CI: 0.841-1.277, p = 0.736). Our findings suggested that high levels of FT3 were significantly associated with NAFLD among middle-aged euthyroid subjects independently of known metabolic risk factors. A negative correlation of serum FT4 level with NAFLD was only observed in pre-menopausal women.

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

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

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

Cosmic muon induced EM showers in NO$$\

DOE PAGES

Yadav, Nitin; Duyang, Hongyue; Shanahan, Peter; ...

2016-11-15

Here, the NuMI Off-Axis v e Appearance (NOvA) experiment is a ne appearance neutrino oscillation experiment at Fermilab. It identifies the ne signal from the electromagnetic (EM) showers induced by the electrons in the final state of neutrino interactions. Cosmic muon induced EM showers, dominated by bremsstrahlung, are abundant in NOvA far detector. We use the Cosmic Muon- Removal technique to get pure EM shower sample from bremsstrahlung muons in data. We also use Cosmic muon decay in flight EM showers which are highly pure EM showers.The large Cosmic-EM sample can be used, as data driven method, to characterize themore » EM shower signature and provides valuable checks of the simulation, reconstruction, particle identification algorithm, and calibration across the NOvA detector.« less

Cosmic muon induced EM showers in NO$$\

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadav, Nitin; Duyang, Hongyue; Shanahan, Peter

Here, the NuMI Off-Axis v e Appearance (NOvA) experiment is a ne appearance neutrino oscillation experiment at Fermilab. It identifies the ne signal from the electromagnetic (EM) showers induced by the electrons in the final state of neutrino interactions. Cosmic muon induced EM showers, dominated by bremsstrahlung, are abundant in NOvA far detector. We use the Cosmic Muon- Removal technique to get pure EM shower sample from bremsstrahlung muons in data. We also use Cosmic muon decay in flight EM showers which are highly pure EM showers.The large Cosmic-EM sample can be used, as data driven method, to characterize themore » EM shower signature and provides valuable checks of the simulation, reconstruction, particle identification algorithm, and calibration across the NOvA detector.« less

Chemical shift magnetic resonance imaging is helpful in detecting hepatic steatosis but not fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).

PubMed

Kalra, Naveen; Duseja, Ajay; Das, Ashim; Dhiman, Radha Krishan; Virmani, Vivek; Chawla, Yogesh; Singh, Paramjee; Khandelwal, Niranjan

2009-01-01

Imaging modalities have a role in the diagnosis of patients with nonalcoholic fatty liver disease. Aim of the present study was to evaluate the role of chemical shift magnetic resonance imaging in assessing hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease. Chemical shift magnetic resonance imaging was done in 10 biopsy proven patients (7 females, mean age 41 +/- 9.2 years) with nonalcoholic fatty liver disease. Objective measurements of signal intensity (SI) were done and a ratio was calculated (SI out-of- phase liver/ SI out-of- phase kidney)/ (SI in- phase liver/ SI in-phase kidney). A lower ratio indicated a higher signal drop and hence higher fat content. The ratio was correlated with hepatic steatosis on histology (< 33% and > 33%). Patients were classified as having histological NASH or no NASH and MRI was assessed in diagnosing hepatic fibrosis as seen on liver histology. Six patients had > 33% hepatic steatosis on histology. Five patients (50%) had evidence of histological NASH. MRI was not helpful in differentiating patients with and without histological NASH. One patient amongst NASH patients did not have fibrosis, one had stage 1, 2 had stage 2 and one had stage 4 fibrosis. SI ratio ranged between 0.35-0.69 in 6 patients with steatosis > 33% and was in the range of 0.69-1.20 in four patients with steatosis < 33% on histology. Fibrotic changes seen in 4 patients on biopsy were not detected on MRI. Chemical shift MRI provides objective data on fat infiltration in patients with NAFLD without giving information about hepatic fibrosis.

Higher body fat percentage is associated with enhanced temperature perception in NAFLD: results from the randomised Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy trial (WELCOME) trial.

PubMed

Clough, Geraldine F; McCormick, Keith G; Scorletti, Eleonora; Bhatia, Lokpal; Calder, Philip C; Griffin, Michael J; Byrne, Christopher D

2016-07-01

The effect of n-3 fatty acid treatment on temperature perception as a sensory nerve function modality is uncertain. In patients with non-alcoholic fatty liver disease (NAFLD) both with and without type 2 diabetes, we: (1) tested whether 15-18 months' treatment with 4 g/day of docosahexaenoic plus eicosapentaenoic acid (DHA+EPA) improved hot (HPT) and cold (CPT) temperature perception thresholds and (2) explored factors associated with HPT and CPT, in a randomised, double-blind, placebo-controlled trial. The effect of treatment (n = 44) on HPT, CPT and temperature perception index (TPI: difference between HPT and CPT) was measured at the big toe in 90 individuals without neuropathy (type 2 diabetes; n = 30). Participants were randomised 1:1, using sequential numbering, by personnel independent from the trial team. All participants and all members of the research team were blinded to group assignment. Data were collected in the Southampton National Institute for Health Research Biomedical Research Centre. Treatment effects and the independence of associations were testing by regression modelling. Mean ± SD age was 50.9 ± 10.6 years. In men (n = 53) and women (n = 37), HPTs (°C) were 46.1 ± 5.1 and 43.1 ± 6.4 (p = 0.02), CPTs (°C) were 22.7 ± 3.4 and 24.5 ± 3.6 (p = 0.07) and TPIs (°C) were 23.4 ± 7.4 and 18.7 ± 9.5 (p = 0.008), respectively. In univariate analyses, total body fat percentage (measured by dual-energy x-ray absorptiometry [DXA]) was associated with HPT (r = -0.36 p = 0.001), CPT (r = 0.35 p = 0.001) and TPI (r = 0.39 p = 0.0001). In multivariable-adjusted regression models, adjusting for age, sex and other potential confounders, only body fat percentage was independently associated with HPT, CPT or TPI (p = 0.006, p = 0.006 and p = 0.002, respectively). DHA+EPA treatment did not modify HPT, CPT or TPI (p = 0.93, p = 0.44 and p = 0

Nonalcoholic fatty liver disease and polycystic ovary syndrome.

PubMed

Vassilatou, Evangeline

2014-07-14

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD.

Nonalcoholic fatty liver disease: Evolving paradigms

PubMed Central

Lonardo, Amedeo; Nascimbeni, Fabio; Maurantonio, Mauro; Marrazzo, Alessandra; Rinaldi, Luca; Adinolfi, Luigi Elio

2017-01-01

In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including ”lean NAFLD” has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible. PMID:29085206

Clinical and Metabolic Characterization of Lean Caucasian Subjects With Non-alcoholic Fatty Liver.

PubMed

Feldman, Alexandra; Eder, Sebastian K; Felder, Thomas K; Kedenko, Lyudmyla; Paulweber, Bernhard; Stadlmayr, Andreas; Huber-Schönauer, Ursula; Niederseer, David; Stickel, Felix; Auer, Simon; Haschke-Becher, Elisabeth; Patsch, Wolfgang; Datz, Christian; Aigner, Elmar

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity; however, 5-8% of lean subjects also have evidence of NAFLD. We aimed to investigate clinical, genetic, metabolic and lifestyle characteristics in lean Caucasian subjects with NAFLD. Data from 187 subjects allocated to one of the three groups according to body mass index (BMI) and hepatic steatosis on ultrasound were obtained: lean healthy (BMI≤25 kg/m 2 , no steatosis, N=71), lean NAFLD (BMI≤25 kg/m 2 , steatosis, N=55), obese NAFLD (BMI≥30 kg/m 2 , steatosis; N=61). All subjects received a detailed clinical and laboratory examination including oral glucose tolerance test. The serum metabolome was assessed using the Metabolomics AbsoluteIDQ p180 kit (BIOCRATES Life Sciences). Genotyping for single-nucleotide polymorphisms (SNPs) associated with NAFLD was performed. Lean NAFLD subjects had fasting insulin concentrations similar to lean healthy subjects but had markedly impaired glucose tolerance. Lean NAFLD subjects had a higher rate of the mutant PNPLA3 CG/GG variant compared to lean controls (P=0.007). Serum adiponectin concentrations were decreased in both NAFLD groups compared to controls (P<0.001 for both groups) The metabolomics study revealed a potential role for various lysophosphatidylcholines (lyso-PC C18:0, lyso-PC C17:0) and phosphatidylcholines (PCaa C36:3; false discovery rate (FDR)-corrected P-value<0.001) as well as lysine, tyrosine, and valine (FDR<0.001). Lean subjects with evidence of NAFLD have clinically relevant impaired glucose tolerance, low adiponectin concentrations and a distinct metabolite profile with an increased rate of PNPLA3 risk allele carriage.

Nonalcoholic fatty liver disease and polycystic ovary syndrome

PubMed Central

Vassilatou, Evangeline

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD. PMID:25024594

Absence of non-alcoholic fatty liver disease in the presence of insulin resistance is a strong predictor for colorectal carcinoma

PubMed Central

Basyigit, Sebahat; Uzman, Metin; Kefeli, Ayse; Sapmaz, Ferdane Pirincci; Yeniova, Abdullah Ozgür; Nazligul, Yasar; Asiltürk, Zeliha

2015-01-01

Background: Colorectal carcinoma (CRC) and non-alcoholic fatty liver disease (NAFLD) share common risk factors. Insulin resistance (IR) has an important role in both diseases. It has been speculated that the prevalence of colorectal neoplasms might be increased in patients with NAFLD. However, It is unclear whether NAFLD is an actual risk factor or any association is incidental coexistance due to the role of IR in both disease. We aimed to assess the risk for CRC in patients with NAFLD in relation to IR. Method: This study was designed prospectively and cross-sectionally. We determined NAFLD by ultrasonography and measured IR by the homeostatic model of assessment-insulin resistance model. Results: The prevalences of CRC and adenoma were shown to be significantly higher in patients with IR (respectively; P: 0.005, P: 0.008). But prevalence of CRC was found to be significantly lower in subjects with NAFLD (P: 0.001). On multivariate logistic regression analysis, the risks of colorectal adenoma and carcinoma were significantly associated with the presence of IR (respectively; OR: 2.338, 95% CI: 1.080-4.993, P: 0.003 and : 5.023, 95% CI: 1.789-9.789, P: 0.001). The risk for CRC was significantly associated with the absence of NAFLD (OR: 7.380, 95% CI: 3.069-7.961, P: 0.010). The absence of NAFLD in the presence of IR was associated with significantly high risk for CRC (OR: 5.218, 95% CI: 1.538-7.448, P: 0.017). Conclusion: The risk of CRC can increased in subjects with IR but without NAFLD. The absence of NAFLD in the presence of IR may predict the CRC. PMID:26770473

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

Changes in drug transport and metabolism and their clinical implications in non-alcoholic fatty liver disease.

PubMed

Dietrich, Christoph G; Rau, Monika; Jahn, Daniel; Geier, Andreas

2017-06-01

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising, especially in Western countries. Drug treatment in patients with NAFLD is common since it is linked to other conditions like diabetes, obesity, and cardiovascular disease. Consequently, changes in drug metabolism may have serious clinical implications. Areas covered: A literature search for studies in animal models or patients with obesity, fatty liver, non-alcoholic steatohepatitis (NASH) or NASH cirrhosis published before November 2016 was performed. After discussing epidemiology and animal models for NAFLD, we summarized both basic as well as clinical studies investigating changes in drug transport and metabolism in NAFLD. Important drug groups were assessed separately with emphasis on clinical implications for drug treatment in patients with NAFLD. Expert opinion: Given the frequency of NAFLD even today, a high degree of drug treatment in NAFLD patients appears safe and well-tolerated despite considerable changes in hepatic uptake, distribution, metabolism and transport of drugs in these patients. NASH causes changes in biliary excretion, systemic concentrations, and renal handling of drugs leading to alterations in drug efficacy or toxicity under specific circumstances. Future clinical drug studies should focus on this special patient population in order to avoid serious adverse events in NAFLD patients.

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.

Gender and racial differences in nonalcoholic fatty liver disease.

PubMed

Pan, Jen-Jung; Fallon, Michael B

2014-05-27

Due to the worldwide epidemic of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of elevated liver enzymes. NAFLD represents a spectrum of liver injury ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which may progress to advanced fibrosis and cirrhosis. Individuals with NAFLD, especially those with metabolic syndrome, have higher overall mortality, cardiovascular mortality, and liver-related mortality compared with the general population. According to the population-based studies, NAFLD and NASH are more prevalent in males and in Hispanics. Both the gender and racial ethnic differences in NAFLD and NASH are likely attributed to interaction between environmental, behavioral, and genetic factors. Using genome-wide association studies, several genetic variants have been identified to be associated with NAFLD/NASH. However, these variants account for only a small amount of variation in hepatic steatosis among ethnic groups and may serve as modifiers of the natural history of NAFLD. Alternatively, these variants may not be the causative variants but simply markers representing a larger body of genetic variations. In this article, we provide a concise review of the gender and racial differences in the prevalence of NAFLD and NASH in adults. We also discuss the possible mechanisms for these disparities.

Updates on Dietary Models of Nonalcoholic Fatty Liver Disease: Current Studies and Insights

PubMed Central

Stephenson, Kristen; Kennedy, Lindsey; Hargrove, Laura; Demieville, Jennifer; Thomson, Joanne; Alpini, Gianfranco; Francis, Heather

2018-01-01

Nonalcoholic fatty liver disease (NAFLD) is a disease of increasing interest, as its prevalence is on the rise. NAFLD has been linked to metabolic syndrome, which is becoming more common due to the Western diet. Because NAFLD can lead to cirrhosis and related complications including hepatocellular carcinoma, the increasing prevalence is concerning, and medical therapy aimed at treating NAFLD is of great interest. Researchers studying the effects of medical therapy on NAFLD use dietary mouse models. The two main types of mouse model diets are the methionine- and choline-deficient (MCD) diet and the Western-like diet (WD). Although both induce NAFLD, the mechanisms are very different. We reviewed several studies conducted within the last 5 years that used MCD diet or WD mouse models in order to mimic this disease in a way most similar to humans. The MCD diet inconsistently induces NAFLD and fibrosis and does not completely induce metabolic syndrome. Thus, the clinical significance of the MCD diet is questionable. In contrast, WD mouse models consisting of high fat, cholesterol, and a combination of high-fructose corn syrup, sucrose, fructose, or glucose not only lead to metabolic syndrome but also induce NAFLD with fibrosis, making these choices most suitable for research. PMID:29096730

The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children.

PubMed

Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia Del Giudice, Emanuele

2017-07-07

The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD) the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD) even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood.

Coffee consumption is not associated with prevalent subclinical cardiovascular disease (CVD) or the risk of CVD events, in nonalcoholic fatty liver disease: Results from the multi-ethnic study of atherosclerosis

USDA-ARS?s Scientific Manuscript database

Atherosclerosis and its clinical sequelae represent the leading cause of mortality among patients with nonalcoholic fatty liver disease (NAFLD). While epidemiologic data support the hepatoprotective benefits of coffee in NAFLD, whether coffee improves NAFLD-associated Cardiovascular Disease (CVD) ri...

The intersection of nonalcoholic fatty liver disease and obesity.

PubMed

Woo Baidal, Jennifer A; Lavine, Joel E

2016-01-27

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and recently emerged as the most rapidly increasing indication for liver transplant. Although obesity is a risk factor for NAFLD, overlap between these two entities is incompletely understood. We highlight recent insights into the pathogenesis of human NAFLD in relation to obesity and discuss advances in the diagnosis and treatment of NAFLD. Copyright © 2016, American Association for the Advancement of Science.

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

Lean nonalcoholic fatty liver disease (NAFLD) is defined as NAFLD that develops in patients with a body mass index (BMI) less than 25 kg/m 2 . We investigated the differences between lean NAFLD and NAFLD in overweight and obese persons, factors associated with the severity of liver and cardiovascular disease, and the effects of visceral obesity. We performed a retrospective cohort study of 669 consecutive patients with biopsy-proven NAFLD seen at 3 liver centers in Italy. We collected anthropometric, clinical, and biochemical data, as well as information on carotid atherosclerosis (artery intima-media thickness and plaque), liver histology (nonalcoholic steatohepatitis [NASH] and fibrosis), insulin resistance, and diabetes. Overweight was defined as a BMI of 25 to 29.9 kg/m 2 , and obese was defined as a BMI of 30 kg/m 2 or greater. Patients were assigned to groups based on waist circumference, a marker of visceral obesity (low: men, <94 cm, women <80 cm; medium: men, 94-102 cm, women 80-88 cm; or high: men >102 cm, women >88 cm). DNA samples were analyzed for the rs738409 C>G (I148M in PNPLA3), the rs58542926 C>T (E167K in TM6SF2), and single-nucleotide polymorphisms. Variables in men and women were analyzed using chi-squared analysis and the Mann-Whitney or Kruskal-Wallis tests. Multiple linear or logistic regression analyses were adjusted for all the variables of clinical relevance or statistically significant at univariate analyses. The primary outcome was the difference in liver and cardiovascular disease between lean NAFLD and NAFLD in overweight and obese persons. Secondary outcomes were effects of visceral obesity, based on waist circumference, on hepatic, vascular, and metabolic features. Significantly lower proportions of patients with lean NAFLD (143 patients; 43 women; mean age, 46 ± 13 y) had hypertension (P = .001), diabetes (P = .0001), and metabolic syndrome (P = .0001) than overweight or obese patients with NAFLD (526 patients; 149 women; mean

Association of Adiponectin Gene Polymorphisms With the Risk of Coronary Artery Disease in Patients With Nonalcoholic Fatty Liver Disease in a Chinese Han Population

PubMed Central

Du, Shui-Xian; Lu, Lin-Lin; Liu, Yang; Dong, Quan-Jiang; Xuan, Shi-Ying; Xin, Yong-Ning

2016-01-01

Background Cardiovascular events are an independent risk factor for nonalcoholic fatty liver disease (NAFLD), which is the leading cause of mortality in NAFLD patients. Several recent studies demonstrated that adiponectin (Ad) polymorphisms were involved in the progression of NAFLD and coronary artery disease (CAD). However, reports on the association between Ad polymorphisms and the risk of developing CAD in NAFLD patients are lacking in a Northern Han Chinese population. Objectives The present study was designed to evaluate the association between Ad gene polymorphisms (rs266729 and rs2241766) and the risk of developing CAD in Northern Han Chinese patients with NAFLD. Materials and Methods In this case-control study, using the polymerase chain reaction (PCR), Adrs266729 and rs2241766 gene polymorphisms were genotyped in B-type ultrasonography-proven NAFLD patients, with (n = 246) or without (n = 247) CAD and in healthy controls (n = 304). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS 17.0 statistical software. Results There were significant differences in the Adrs266729 G allele between the NAFLD patients with and without CAD (P < 0.05). In addition, there was a significant difference in the Adrs2241766 G allele of the NAFLD patients compared with that of the controls (P < 0.05). In the NAFLD CAD population, carriers of the G allele of Adrs266729 had higher serum triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG), and low-density lipoprotein (LDL) levels and a lower Ad level than their noncarrier counterparts (P = 0.031, P = 0.034, P = 0.007, P < 0.001, and P < 0.001, respectively). NAFLD patients without CAD had higher TG and serum FPG values and a lower Ad level than their noncarrier counterparts (P = 0.014, P = 0.038, and P < 0.001, respectively). In the NAFLD patients with/without CAD, the carriers of the G allele of Adrs2241766 had higher TG levels (P = 0.039 and P = 0

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

A emissão em 8mm e as bandas de Merrill-Sanford em estrelas carbonadas

NASA Astrophysics Data System (ADS)

de Mello, A. B.; Lorenz-Martins, S.

2003-08-01

Estrelas carbonadas possuem bandas moleculares em absorção no visível e, no infravermelho (IR) as principais características espectrais se devem a emissão de grãos. Recentemente foi detectada a presença de bandas de SiC2 (Merrill-Sanford, MS) em emissão sendo atribuída à presença de um disco rico em poeira. Neste trabalho analisamos uma amostra de 14 estrelas carbonadas, observadas no telescópio de 1.52 m do ESO em 4 regiões espectrais diferentes, a fim de detectar as bandas de MS em emissão. Nossa amostra é composta de estrelas que apresentam além da emissão em 11.3 mm, outra em 8 mm. Esta última emissão, não usual nestes objetos, tem sido atribuída ou a moléculas de C2H2, ou a um composto sólido ainda indefinido. A detecção de emissões de MS e aquelas no IR, simultaneamente, revelaria um cenário mais complexo que o habitualmente esperado para os ventos destes objetos. No entanto como primeiro resultado, verificamos que as bandas de Merrill-Sanford encontram-se em absorção, não revelando nenhuma conexão com a emissão a 8 mm. Assim, temos duas hipóteses: (a) a emissão a 8 mm se deve à molécula C2H2 ou (b) essa emissão é resultado da emissão térmica de grãos. Testamos a segunda hipótese modelando a amostra com grãos não-homogêneos de SiC e quartzo, o qual emite em aproximadamente 8mm. Este grão seria produzido em uma fase evolutiva anterior a das carbonadas (estrelas S) e por terem uma estrutura cristalina são destruídos apenas na presença de campos de radiação ultravioleta muito intensos. Os modelos para os envoltórios utilizam o método de Monte Carlo para descrever o problema do transporte da radiação. As conclusões deste trabalho são: (1) as bandas de Merrill-Sanford se encontram em absorção, sugerindo um cenário usual para os ventos das estrelas da amostra; (2) neste cenário, a emissão em 8 mm seria resultado de grãos de quartzo com mantos de SiC, indicando que o quartzo poderia sobreviver a fase

The Orthogonally Partitioned EM Algorithm: Extending the EM Algorithm for Algorithmic Stability and Bias Correction Due to Imperfect Data.

PubMed

Regier, Michael D; Moodie, Erica E M

2016-05-01

We propose an extension of the EM algorithm that exploits the common assumption of unique parameterization, corrects for biases due to missing data and measurement error, converges for the specified model when standard implementation of the EM algorithm has a low probability of convergence, and reduces a potentially complex algorithm into a sequence of smaller, simpler, self-contained EM algorithms. We use the theory surrounding the EM algorithm to derive the theoretical results of our proposal, showing that an optimal solution over the parameter space is obtained. A simulation study is used to explore the finite sample properties of the proposed extension when there is missing data and measurement error. We observe that partitioning the EM algorithm into simpler steps may provide better bias reduction in the estimation of model parameters. The ability to breakdown a complicated problem in to a series of simpler, more accessible problems will permit a broader implementation of the EM algorithm, permit the use of software packages that now implement and/or automate the EM algorithm, and make the EM algorithm more accessible to a wider and more general audience.

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

Glycosyltransferases and non-alcoholic fatty liver disease

PubMed Central

Zhan, Yu-Tao; Su, Hai-Ying; An, Wei

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized. PMID:26937136

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.

Non-alcoholic fatty liver disease predicts type 2 diabetes mellitus, but not prediabetes, in Xi'an, China: a five-year cohort study.

PubMed

Ming, Jie; Xu, Shaoyong; Gao, Bin; Liu, Guocai; Ji, Yufei; Yang, Fan; Jia, Yunan; Fang, Yujie; Ji, Qiuhe

2015-11-01

Emerging studies have focused the association between non-alcoholic fatty liver disease (NAFLD) and the risk of type 2 diabetes mellitus (T2DM) but the results were inconsistent. In addition, few studies have put focus on the association between NAFLD and the risk of prediabetes. We aimed to investigate whether NAFLD diagnosed by ultrasonography could predict the risk of future T2DM and prediabetes in Chinese population. The population-based cohort study held in Xi'an, Northwestern China, was based on China National Diabetes and Metabolic Disorders Survey. During a follow-up of 5 years, 508 healthy subjects were included as study sample. NAFLD was determined by abdominal ultrasonography. T2DM and prediabetes were diagnosed based on oral glucose tolerance test. Of 508 subjects, 97 (19.1%) were diagnosed as NAFLD and 411 (80.9%) were as non-NAFLD; 20 (3.9%) developed diabetes and 85 (16.7%) developed prediabetes during follow-up. The incidence of diabetes and prediabetes in the NAFLD group was 20.6 and 51.6 per 1000 person-years, respectively, whereas that in non-NAFLD group was 4.9 and 29.2 per 1000 person-years respectively. Cox proportional hazard regression showed that the multivariable-adjusted relative risk (RR) of T2DM and prediabetes in the NAFLD group was 4.462 [95% confidence interval (CI): 1.855-10.734, P < 0.001] and 1.642 (95% CI: 0.965-2.793, P = 0.067), respectively, compared with non-NAFLD group. Non-alcoholic fatty liver disease was a significant predictor for future diabetes, but not for prediabetes, in Xi'an, China. More cohort studies are needed to confirm our findings. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels.

PubMed

Portillo-Sanchez, Paola; Bril, Fernando; Maximos, Maryann; Lomonaco, Romina; Biernacki, Diane; Orsak, Beverly; Subbarayan, Sreevidya; Webb, Amy; Hecht, Joan; Cusi, Kenneth

2015-06-01

Nonalcoholic fatty liver disease (NAFLD) and its more severe form with steatohepatitis (NASH) are common in patients with type 2 diabetes mellitus (T2DM). However, they are usually believed to largely affect those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD by the gold standard, liver magnetic resonance spectroscopy ((1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. We recruited 103 patients with T2DM and normal plasma aminotransferases (age, 60 ± 8 y; body mass index [BMI], 33 ± 5 kg/m(2); glycated hemoglobin [A1c], 7.6 ± 1.3%). We measured the following: 1) liver triglyceride content by (1)H-MRS; 2) systemic insulin sensitivity (homeostasis model assessment-insulin resistance); and 3) adipose tissue insulin resistance, both fasting (as the adipose tissue insulin resistance index: fasting plasma free fatty acids [FFA] × insulin) and during an oral glucose tolerance test (as the suppression of FFA). The prevalence of NAFLD and NASH were much higher than expected (50% and 56% of NAFLD patients, respectively). The prevalence of NAFLD was higher in obese compared with nonobese patients as well as with increasing BMI (P = .001 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (P = .01). Compared with nonobese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle) and, particularly, adipose tissue (fasting/postprandial) insulin resistance (all P < .01). The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of NASH. Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH.

Type 2 diabetes mellitus and non-alcoholic fatty liver disease: a systematic review and meta-analysis.

PubMed

Amiri Dash Atan, Nasrin; Koushki, Mehdi; Motedayen, Morteza; Dousti, Majid; Sayehmiri, Fatemeh; Vafaee, Reza; Norouzinia, Mohsen; Gholami, Reza

2017-01-01

The aim of this study was the evaluation of the prevalence of NAFLD in patients with type 2 diabetes mellitus. Non-alcoholic fatty liver disease (NAFLD) is an emerging disease with high prevalence in patients with type 2 diabetes mellitus (T2DM). Many studies have reported the prevalence of NAFLD in type 2 diabetes mellitus patients. However, these results are inconsistent. A Literature search was conducted in PubMed, Scopus, web of science and Science Direct from 2005 to August 2017. The necessary information was extracted. Heterogeneity was evaluated using I 2 statistic. Meta-regression analyses were performed to the estimation of the relationship between the year of study and sample size with the prevalence of NAFLD. Publication bias was assessed by both Begg rank correlation and Egger tests. Subgroup analysis was performed for identification of sources heterogeneity. Seventeen studies involving 10897 type 2 diabetes mellitus patients with NAFLD were included in this meta-analysis. The overall prevalence of NAFLD in type 2 diabetes mellitus patients by random effects models was 54% (95% CI, 45%- 64%). There is a significant heterogeneity across studies with (I 2 = 99%, p> 0.01). The funnel plot as graphically and Begg and Egger as statistically showed no publication bias among studies. Subgroup analysis indicated that the prevalence of NAFLD in type 2 diabetes mellitus patients differed in predictive factors such as lipid profile, BMI, HbA1c, AST, and ALT. This finding in spite of heterogeneity of documents is corresponding to the positive correlation between NAFLD and type 2 diabetes mellitus. The findings indicated that the overall prevalence of NAFLD among type 2 diabetes mellitus patients is significantly higher. It can be concluded that type 2 diabetes mellitus patients should be managed to prevent NAFLD.

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.

Associations between longer habitual day napping and non-alcoholic fatty liver disease in an elderly Chinese population.

PubMed

Qu, Hua; Wang, Hang; Deng, Min; Wei, Huili; Deng, Huacong

2014-01-01

Both longer habitual day napping and Non-Alcoholic Fatty Liver Disease (NAFLD) are associated with diabetes and inflammation, but the association between day napping and NAFLD remains unexplored. To investigate the association between the duration of habitual day napping and NAFLD in an elderly Chinese population and to gain insight into the role of inflammatory cytokines in this association. We conducted a series of cross-sectional studies of the community population in Chongqing, China, from 2011 to 2012. Among 6998 participants aged 40 to 75 years, 6438 eligible participants were included in the first study and analyzed to observe the association between day napping duration and NAFLD. In a separate study, 80 non-nappers and 90 nappers were selected to identify the role of inflammatory cytokines in this association. Logistic regression models were used to examine the odds ratios (ORs) of day nap duration with NAFLD. Day nappers had a significantly higher prevalence of NAFLD (P<0.001). Longer day napping duration was associated in a dose-dependent manner with NAFLD (P trend <0.001). After adjustment for potential confounders, the ORs were 1.67 (95% CI 1.13-2.46) for those reporting 0.5-1 h and 1.49 (95% CI 1.01-2.19) for those reporting >1 h of day napping compared with individuals who did not take day naps (all P<0.05). Longer-duration day nappers had higher levels of IL-6 and progranulin (PGRN) but lower levels of Secreted frizzled-related protein-5 (SFRP5, all P trend <0.001). After adjusting for IL-6, PGRN, and SFRP5, the association between day napping duration and NAFLD disappeared (all P>0.05). Longer day napping duration is associated with a higher prevalence of NAFLD, and inflammatory cytokines may be an essential link between day napping and NAFLD.

Screening for non-alcoholic fatty liver disease in children and adolescents with type 1 diabetes mellitus: a cross-sectional analysis.

PubMed

Kummer, Sebastian; Klee, Dirk; Kircheis, Gerald; Friedt, Michael; Schaper, Joerg; Häussinger, Dieter; Mayatepek, Ertan; Meissner, Thomas

2017-04-01

The liver is intensely involved in glucose metabolism and is thereby closely related to diabetes pathophysiology. Adult patients with type 1 diabetes mellitus (DM) are at an increased risk for non-alcoholic fatty liver disease (NAFLD). Here, we studied the prevalence of NAFLD in a cohort of children and adolescents with type 1 DM in a tertiary care paediatric diabetes centre in Germany. We screened 93 children and adolescents with type 1 DM using ultrasound, laboratory investigations, and liver stiffness measurements (Fibroscan® [FS] and acoustic radiation force imaging [ARFI]). Of these, 82 (88.1%) had completely normal results in all examined aspects. Only one patient (1.1%) fulfilled the criteria as potential NAFLD with ALT > twice the upper limit of normal. Ten of the 93 patients (10.8%) showed any mild abnormality in at least one examined category including ALT, conventional ultrasounds and liver stiffness measurements. However, none of these ten fulfilled the NAFLD case definition criteria. Therefore, these slightly abnormal results were judged to be unspecific or at least of unknown significance in terms of NAFLD indication. Compared to data from the general population, our results do not indicate a significantly increased prevalence of NAFLD in this cohort, and advocate against the systematic screening for NAFLD in paediatric type 1 DM. What is Known: • Non-alcoholic fatty liver disease (NAFLD) is common in adults with type 1 DM, and paediatric patients with type 1 DM in Egypt and Saudi Arabia. What is New: • Our results do not indicate a significantly increased prevalence of NAFLD in a cohort of children and adolescents with type 1 DM from Germany compared to prevalence data from the general population. • This finding advocates against the systematic screening for NAFLD in paediatric type 1 DM in western countries.

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.

Short sleep duration and longer daytime napping are associated with non-alcoholic fatty liver disease in Chinese adults.

PubMed

Peng, Kui; Lin, Lin; Wang, Zhengyi; Ding, Lin; Huang, Ya; Wang, Po; Xu, Yu; Lu, Jieli; Xu, Min; Bi, Yufang; Wang, Weiqing; Chen, Yuhong; Ning, Guang

2017-09-01

Epidemiologic studies have reported conflicting results on the relationship between short sleep duration and non-alcoholic fatty liver disease (NAFLD). There are no previous studies investigating the effect of daytime napping on NAFLD. In the present study we examined the associations between NAFLD and both nightly sleep duration and daytime napping in a middle-aged and elderly Chinese population. This cross-sectional community-based population study was performed on 8559 individuals aged ≥40 years. Sleep duration and the duration of daytime napping were self-reported using a standardized questionnaire; NAFLD was diagnosed by ultrasonography. In this study sample, the overall prevalence of NAFLD was 30.4%. There was an inverse association between sleep duration and the risk of prevalent NAFLD. In multivariate analysis, the odds ratios (ORs) and 95% confidence intervals (CIs) of prevalent NAFLD for decreasing sleep duration categories (≥9, 8.1-9, 7.1-8, 6.1-7, and ≤6.1 h) were 1.00 (reference), 1.38 (1.13-1.70), 1.32 (1.08-1.61), 1.29 (1.04-1.60), and 1.66 (1.28-2.15), respectively (P trend  = 0.0073). Compared with participants without a daytime napping habit, nap takers with a longer nap duration (>0.5 h) had an increased risk of prevalent NAFLD (OR 1.22; 95% CI 1.06-1.41). The associations of sleep duration and daytime napping duration with NAFLD were generally consistent across different categories of age and obesity, metabolic syndrome, and insulin resistance status. Short sleep duration and longer daytime napping were associated with an increased risk of prevalent NAFLD in a middle-aged and elderly Chinese population. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Cannabis use is associated with reduced prevalence of non-alcoholic fatty liver disease: A cross-sectional study.

PubMed

Adejumo, Adeyinka Charles; Alliu, Samson; Ajayi, Tokunbo Opeyemi; Adejumo, Kelechi Lauretta; Adegbala, Oluwole Muyiwa; Onyeakusi, Nnaemeka Egbuna; Akinjero, Akintunde Micheal; Durojaiye, Modupeoluwa; Bukong, Terence Ndonyi

2017-01-01

Cannabis use is associated with reduced prevalence of obesity and diabetes mellitus (DM) in humans and mouse disease models. Obesity and DM are a well-established independent risk factor for non-alcoholic fatty liver disease (NAFLD), the most prevalent liver disease globally. The effects of cannabis use on NAFLD prevalence in humans remains ill-defined. Our objective is to determine the relationship between cannabis use and the prevalence of NAFLD in humans. We conducted a population-based case-control study of 5,950,391 patients using the 2014 Healthcare Cost and Utilization Project (HCUP), Nationwide Inpatient Survey (NIS) discharge records of patients 18 years and older. After identifying patients with NAFLD (1% of all patients), we next identified three exposure groups: non-cannabis users (98.04%), non-dependent cannabis users (1.74%), and dependent cannabis users (0.22%). We adjusted for potential demographics and patient related confounders and used multivariate logistic regression (SAS 9.4) to determine the odds of developing NAFLD with respects to cannabis use. Our findings revealed that cannabis users (dependent and non-dependent) showed significantly lower NAFLD prevalence compared to non-users (AOR: 0.82[0.76-0.88]; p<0.0001). The prevalence of NAFLD was 15% lower in non-dependent users (AOR: 0.85[0.79-0.92]; p<0.0001) and 52% lower in dependent users (AOR: 0.49[0.36-0.65]; p<0.0001). Among cannabis users, dependent patients had 43% significantly lower prevalence of NAFLD compared to non-dependent patients (AOR: 0.57[0.42-0.77]; p<0.0001). Our observations suggest that cannabis use is associated with lower prevalence of NAFLD in patients. These novel findings suggest additional molecular mechanistic studies to explore the potential role of cannabis use in NAFLD development.

Assessment of Lean Patients with Non-alcoholic Fatty Liver Disease in a Middle Income Country; Prevalence and Its Association with Metabolic Disorders: A Cross-sectional Study.

PubMed

Naderian, Mohammadreza; Kolahdoozan, Shadi; Sharifi, Amir Sina; Garmaroudi, Gholamreza; Yaseri, Mehdi; Poustchi, Hossein; Sohrabpour, Amir Ali

2017-04-01

Recent data has proven that the WHO (world health organization) cut-off for obesity is not applicable to the Asian population. This study aims to estimate the prevalence of lean NAFLD (non-alcoholic fatty liver disease) in the capital of Iran and extract probable predictors for this growing health issue in this population. This is a population-based cross-sectional study on apparently healthy subjects over 18 years of age. The participants were interviewed for baseline demographic and clinical information. They were subsequently referred for physical examination and blood sampling. NAFLD was diagnosed using abdominal ultrasonography by a single expert radiologist. Of 927 eligible participants who entered the study, 314 were lean; BMI (body mass index) <25 kg/m2. The prevalence of NAFLD was 17.52% (95% Exact CI: 13.48%-22.18%). BMI, SBP (systolic blood pressure), DBP (diastolic blood pressure), total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein) and triglyceride were significantly different in patients with NAFLD. In the final multiple analysis, higher levels of triglyceride, upper SBP and higher BMI even in the range of less than 25 kg/m2 were independent predictors of NAFLD in lean participants. In lean participants with more components of metabolic syndrome, the prevalence of NAFLD increased significantly (all P < 0.01). BMI cut-offs in men and women along with waist circumference cut-off in men could significantly predict the presence of NAFLD in lean patients. After comparing these values, McNemar test showed that BMI cut-offs are more robust than waist circumference cut-offs for predicting the presence of NAFLD in lean subjects (P < 0.01). The prevalence of NAFLD in lean subjects in a sample of Iranian population is 17.52%. Hypertriglyceridemia, higher SBP, and higher BMI especially over 23.2 are independent factors associated with the presence of NAFLD in lean subjects.

Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease: A long-term follow-up study.

PubMed

Hagström, Hannes; Nasr, Patrik; Ekstedt, Mattias; Hammar, Ulf; Stål, Per; Hultcrantz, Rolf; Kechagias, Stergios

2018-01-01

Most patients with nonalcoholic fatty liver disease (NAFLD) are overweight or obese. However, a significant proportion of patients have a normal body mass index (BMI), denoted as lean NAFLD. The long-term prognosis of lean NAFLD is unclear. We conducted a cohort study of 646 patients with biopsy-proven NAFLD. Patients were defined as lean (BMI < 25.0), overweight (BMI 25.0-29.9), or obese (BMI ≥ 30.0) at the time of biopsy. Each case was matched for age, sex, and municipality to 10 controls. Overall mortality and development of severe liver disease were evaluated using population-based registers. Cox regression models adjusted for age, sex, type 2 diabetes, and fibrosis stage were used to examine the long-term risk of mortality and liver-related events in lean and nonlean NAFLD. Lean NAFLD was seen in 19% of patients, while 52% were overweight and 29% were obese. Patients with lean NAFLD were older, had lower transaminases, lower stages of fibrosis, and lower prevalence of nonalcoholic steatohepatitis at baseline compared to patients with a higher BMI. During a mean follow-up of 19.9 years (range 0.4-40 years) representing 12,631 person years and compared to patients who were overweight, patients with lean NAFLD had no increased risk for overall mortality (hazard ratio 1.06; P =  0.73) while an increased risk for development of severe liver disease was found (hazard ratio 2.69; P =  0.007). Conclusion : Although patients with lean NAFLD have lower stages of fibrosis, they are at higher risk for development of severe liver disease compared to patients with NAFLD and a higher BMI, independent of available confounders. ( Hepatology Communications 2018;2:48-57).

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.

[Risk factors analysis of nonalcoholic fatty liver disease in Chinese men].

PubMed

Zheng, Rui-Dan; Zhuang, Qun-Ying; Chen, Jian-Neng; Chen, Jie; Lu, Yan-Hui

2013-01-01

To explore risk factors of nonalcoholic fatty liver disease (NAFLD) in men in order to provide a theoretical basis for developing more effective NAFLD prevention and control strategies. One-hundred-and-two male patients (37.3+/-11.4 years old) hospitalized with NAFLD at the Dongnan Affiliated Hospital of Xiamen University between January 2009 and December 2010 were enrolled in the study, along with 23 age-matched healthy men (34.4+/-16.7 years old) to serve as the control group. The correlation(s) of body mass index (BMI; overweight defined as more than or equal to 22.717 kg/m2), waist circumference (WC), waist-to-hip ratio (WHR; central obesity defined as more than or equal to 0.866), fasting plasma glucose (FPG), triglyceride (TG), and total cholesterol (TC) with NAFLD was analyzed by univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to select proper thresholds for classification. BMI, WC, WHR, FPG, TG, and TC were significantly different between the cases and controls (P less than 0.01). BMI, WC, WHR, TG and TC were identified as risk factors of NAFLD in these male cases (P less than 0.01). Relative to WC, TG and TC, both BMI and WHR had significant predictive value for NAFLD (odds ratio (OR) = 10.819 and 10.588, respectively). In addition, BMI had the highest diagnostic value for the prediction of NAFLD (area under the curve (AUC) = 0.931) followed by WHR (AUC = 0.879). BMI, WC, WHR, TG, and TC are risk factors of NAFLD in Chinese men. BMI and WHR are effective anthroposomatology indices of NAFLD and may be useful factors on which to base future prevention and early diagnosis strategies for NAFLD in males.

Pain from the life cycle perspective: Evaluation and Measurement through psychophysical methods of category estimation and magnitude estimation.

PubMed

Sousa, Fátima Aparecida Emm Faleiros; Silva, Talita de Cássia Raminelli da; Siqueira, Hilze Benigno de Oliveira Moura; Saltareli, Simone; Gomez, Rodrigo Ramon Falconi; Hortense, Priscilla

2016-08-18

to describe acute and chronic pain from the perspective of the life cycle. participants: 861 people in pain. The Multidimensional Pain Evaluation Scale (MPES) was used. in the category estimation method the highest descriptors of chronic pain for children/ adolescents were "Annoying" and for adults "Uncomfortable". The highest descriptors of acute pain for children/adolescents was "Complicated"; and for adults was "Unbearable". In magnitude estimation method, the highest descriptors of chronic pain was "Desperate" and for descriptors of acute pain was "Terrible". the MPES is a reliable scale it can be applied during different stages of development. descrever a dor aguda e a crônica na perspectiva do ciclo vital. Métodos: participaram 861 pessoas com dor. Foi utilizada a Escala Multidimensional de Avaliação da Dor (EMADOR). Resultados: no método da estimação de categoria o descritor da dor crônica de maior atribuição para crianças e adolescentes foi "Chata" e para adultos foi "Desconfortável". Os descritores de maior atribuição para dor aguda em crianças e adolescentes foram "Complicada" e em adultos "Insuportável". No método de estimação de magnitude, o descritor de maior atribuição na dor crônica foi "Atormentadora" e na dor aguda foi "Terrível". a EMADOR é uma escala confiável e pode ser utilizada nas diferentes etapas do desenvolvimento humano. la descripción del dolor agudo y crónico desde las perspectiva del ciclo de vida. participaron 861 personas con dolor. Se utilizó la Escala Multidimensional de Evaluación del Dolor (EMEDOR). en el método de estimación de categoría el descriptor de dolor crónico más alto para niños y adolescentes fue de Molesto y para adultos fue Incómodo. Los descriptores mayores de dolor agudo para niños y adolescentes fueron Complejo y para adultos Insoportable. En el método de estimación de magnitud, el mayor descriptor de dolor crónico fueron Atormentador y el mayor de dolor agudo fue Terrible

Non-alcoholic fatty liver and the gut microbiota.

PubMed

Bashiardes, Stavros; Shapiro, Hagit; Rozin, Shachar; Shibolet, Oren; Elinav, Eran

2016-09-01

Non-alcoholic fatty liver (NAFLD) is a common, multi-factorial, and poorly understood liver disease whose incidence is globally rising. NAFLD is generally asymptomatic and associated with other manifestations of the metabolic syndrome. Yet, up to 25% of NAFLD patients develop a progressive inflammatory liver disease termed non-alcoholic steatohepatitis (NASH) that may progress towards cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. In recent years, several lines of evidence suggest that the gut microbiome represents a significant environmental factor contributing to NAFLD development and its progression into NASH. Suggested microbiome-associated mechanisms contributing to NAFLD and NASH include dysbiosis-induced deregulation of the gut endothelial barrier function, which facilitates systemic bacterial translocation, and intestinal and hepatic inflammation. Furthermore, increased microbiome-modulated metabolites such as lipopolysaccharides, short chain fatty acids (SCFAs), bile acids, and ethanol, may affect liver pathology through multiple direct and indirect mechanisms. Herein, we discuss the associations, mechanisms, and clinical implications of the microbiome's contribution to NAFLD and NASH. Understanding these contributions to the development of fatty liver pathogenesis and its clinical course may serve as a basis for development of therapeutic microbiome-targeting approaches for treatment and prevention of NAFLD and NASH. Intestinal host-microbiome interactions play diverse roles in the pathogenesis and progression of NAFLD and NASH. Elucidation of the mechanisms driving these microbial effects on the pathogenesis of NAFLD and NASH may enable to identify new diagnostic and therapeutic targets of these common metabolic liver diseases. This article is part of a special issue on microbiota.

Coffee consumption and risk of nonalcoholic fatty liver disease: a systematic review and meta-analysis.

PubMed

Wijarnpreecha, Karn; Thongprayoon, Charat; Ungprasert, Patompong

2017-02-01

Nonalcoholic fatty liver disease (NAFLD) is a worldwide public health concern. Coffee might have a protective effect against NAFLD. However, the results of previous reports are conflicting. Therefore, we carried out this meta-analysis to summarize all available data. This study consisted of two meta-analyses. The first meta-analysis included observational studies comparing the risk of NAFLD in patients who did and did not drink coffee. The second analysis included studies comparing the risk of liver fibrosis between NAFLD patients who did and did not drink coffee. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated. Out of 355 articles, five studies fulfilled our eligibility criteria and were included in the analysis. The risk of NAFLD in patients who drank coffee was significantly lower than that in patients who did not pooled RR 0.71 (95% CI, 0.60-0.85). We also found a significantly decreased risk of liver fibrosis among NAFLD patients who drank coffee compared with those who did not, with a pooled RR of 0.70 (95% CI, 0.60-0.82). However, it should be noted that the definition of regular coffee consumption varied between studies, which is the main limitation of this meta-analysis. Our study found a significantly decreased risk of NAFLD among coffee drinkers and significantly decreased risk of liver fibrosis among patients with NAFLD who drank coffee on a regular basis. Whether consumption of coffee could be considered a preventative measure against NAFLD needs further investigations.

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.

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.

Relationship between Resting Heart Rate, Blood Pressure and Pulse Pressure in Adolescents.

PubMed

Christofaro, Diego Giulliano Destro; Casonatto, Juliano; Vanderlei, Luiz Carlos Marques; Cucato, Gabriel Grizzo; Dias, Raphael Mendes Ritti

2017-05-01

High resting heart rate is considered an important factor for increasing mortality chance in adults. However, it remains unclear whether the observed associations would remain after adjustment for confounders in adolescents. To analyze the relationship between resting heart rate, blood pressure and pulse pressure in adolescents of both sexes. A cross-sectional study with 1231 adolescents (716 girls and 515 boys) aged 14-17 years. Heart rate, blood pressure and pulse pressure were evaluated using an oscillometric blood pressure device, validated for this population. Weight and height were measured with an electronic scale and a stadiometer, respectively, and waist circumference with a non-elastic tape. Multivariate analysis using linear regression investigated the relationship between resting heart rate and blood pressure and pulse pressure in boys and girls, controlling for general and abdominal obesity. Higher resting heart rate values were observed in girls (80.1 ± 11.0 beats/min) compared to boys (75.9 ± 12.7 beats/min) (p ≤ 0.001). Resting heart rate was associated with systolic blood pressure in boys (Beta = 0.15 [0.04; 0.26]) and girls (Beta = 0.24 [0.16; 0.33]), with diastolic blood pressure in boys (Beta = 0.50 [0.37; 0.64]) and girls (Beta = 0.41 [0.30; 0.53]), and with pulse pressure in boys (Beta = -0.16 [-0.27; -0.04]). This study demonstrated a relationship between elevated resting heart rate and increased systolic and diastolic blood pressure in both sexes and pulse pressure in boys even after controlling for potential confounders, such as general and abdominal obesity. A frequência cardíaca de repouso é considerada um importante fator de aumento de mortalidade em adultos. Entretanto, ainda é incerto se as associações observadas permanecem após ajuste para fatores de confusão em adolescentes. Analisar a relação entre frequência cardíaca de repouso, pressão arterial e pressão de pulso em adolescentes dos dois sexos. Estudo transversal

EMS Agenda for the Future

DOT National Transportation Integrated Search

1996-09-01

The National Highway Traffic Safety Administration (NHTSA) and the Health Resources and Services Administration, Maternal and Child Health Bureau sponsored The EMS Agenda for the Future. This document focuses on aspects of EMS related to emergency ca...

Prediction of Supersonic Store Separation Characteristics Including Fuselage and Stores of Noncircular Cross Section. Volume II. Users Manual for the Computer Program.

DTIC Science & Technology

1980-11-01

CMACH $ FMACH) 132 TRJTRY STOP normal termination (test: TIME > TIMEF-0.00001 or NDIFEQ = 1) BDCOEF message warning - NAFLD exceeds blank common...BDCOEF**, NTAP7- , IUB= , NAFLD = . (Test: NAFLD > NADIM) CRFWBD STOP 001 (Test: NER > 1; equation solution singular) INVER2 STOP **Matrix is singular

Waist-to-height ratio is a useful index for nonalcoholic fatty liver disease in children and adolescents: a secondary data analysis.

PubMed

Lin, Ming-Shyan; Lin, Tsai-Hui; Guo, Su-Er; Tsai, Ming-Horng; Chiang, Ming-Shin; Huang, Tung-Jung; Chen, Mei-Yen

2017-10-30

Nonalcoholic fatty liver disease (NAFLD) is a global problem and pediatric obesity has risen dramatically. Early NAFLD might progress to nonalcoholic steatohepatitis (NASH) or liver cirrhosis and significantly increase liver disease-related mortality. We looked for NAFLD predictors in children and adolescents. This community-based, cross-sectional study ran from December 2012 to September 2013 in southwestern Taiwan. Children <10 and >19 years old, with detected hepatic diseases, or who drank alcohol were excluded. The diagnosis of NAFLD was based on ultrasound: age, sex, anthropometric measurements, and laboratory data were evaluated for associated risks by using logistic regression analysis. Receiver operating characteristic (ROC) curves were used to determine cutoff values. We enrolled one thousand, two hundred and ten children (594 males; 616 females; mean age: 15.5 ± 2.8 years). Age, anthropometric measurements, and laboratory data were significantly higher in children with NAFLD. The association between NAFLD and the waist-to-height ratio (WHtR) was significant (adjusted odds ratio: 2.6; 95% confidence interval: 1.909-3.549; P < 0.001). It indicated highly suspicion of NAFLD (sensitivity: 70.1%; specificity 76.9%) when the WHtR for children and adolescents is above the cutoff value of 0.469. The WHtR might be a powerful index of the severity of pediatric NAFLD.

Similarities and differences between pediatric and adult nonalcoholic fatty liver disease.

PubMed

Crespo, Maricruz; Lappe, Sara; Feldstein, Ariel E; Alkhouri, Naim

2016-08-01

Nonalcoholic fatty liver disease (NAFLD) is highly common and potentially serious in children and adolescents. The term NAFLD refers to a spectrum of diseases ranging from accumulation of fat in the liver (simple steatosis or nonalcoholic fatty liver "NAFL") to the potentially progressive form of nonalcoholic steatohepatitis (NASH) characterized by hepatocyte ballooning, inflammation, and often associated with fibrosis. While large prospective longitudinal studies in pediatric NAFLD are still lacking, growing evidence suggests that children with NAFL are at increased risk for cardiometabolic complications, while those with NASH and advance fibrosis are also at risk for significant liver-related morbidity including cirrhosis and its complications. Pediatric NAFLD shares features of adult NAFLD but also shows many different characteristics in terms of prevalence, histology, diagnosis and management. Translational studies suggest that NAFLD is a highly heritable disease in which genetic variations and environment closely interact to determine the disease phenotype and the progression to the more advanced forms of the disease. Changes in lifestyle, targeting gradual weight reduction, and physical exercise continue to be the mainstay of treatment for NAFLD in children. Recent advances in development of noninvasive diagnostic modalities and the potential for identifying effective pharmacological interventions may result in significant progress in the management of NAFLD in the pediatric population. Copyright © 2016 Elsevier Inc. All rights reserved.

Retinol Binding Protein-4 Levels and Non-alcoholic Fatty Liver Disease: A community-based cross-sectional study.

PubMed

Chen, Xuechen; Shen, Tianran; Li, Qing; Chen, Xu; Li, Yanping; Li, Dan; Chen, Gengdong; Ling, Wenhua; Chen, Yu-Ming

2017-03-23

Previous reports on the association between retinol binding protein 4 (RBP4) and nonalcoholic fatty liver disease (NAFLD) were controversial. This study aimed to investigate the association between the serum RBP4 levels and occurrence of NAFLD in Chinese population. In total, 2938 participants aged 40-75 years were involved in this community-based cross-sectional study. General information, lifestyle factors, serum levels of RBP4 and the presence of NAFLD were determined. Patients with NAFLD had significantly higher concentrations of RBP4 (37.9 ± 6.8 μg/ml) than did non-NAFLD controls (35.0 ± 6.7 μg/ml) (P < 0.001). The odds ratios (ORs) of NAFLD for the highest (vs. lowest) quartile of RBP4 were 1.884 (95% CI: 1.391, 2.551) for females (P < 0.001), and 2.107 (95% CI: 1.357, 3.273) for male participants (P < 0.01) after adjusting for related factors. The serum RBP4 levels were positively associated with the prevalence of NAFLD in middle-aged and elderly Chinese people, and Homeostatic model assessment-insulin resistance (HOMA-IR), trunk fat, the waist-to-hip ratio (WHR), systolic blood pressure (SBP), fasting insulin, high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) might be implicated in the pathogenesis of RBP4 in NAFLD.

Serum bile acid level and fatty acid composition in Chinese children with non-alcoholic fatty liver disease.

PubMed

Lu, Li Ping; Wan, Yan Ping; Xun, Peng Cheng; Zhou, Ke Jun; Chen, Cheng; Cheng, Si Yang; Zhang, Min Zhong; Wu, Chun Hua; Lin, Wei Wei; Jiang, Ying; Feng, Hai Xia; Wang, Jia Lu; He, Ka; Cai, Wei

2017-08-01

To determine serum bile acid (BA) and fatty acid (FA) profiles in Chinese children with non-alcoholic fatty liver disease (NAFLD). A total 76 children aged 4-17 years were categorized into three groups according to the presence and absence of as well as the severity of NAFLD, that is, non-NAFLD (control), mild and moderate to severe NAFLD groups, respectively, based on their liver ultrasonography findings. Serum BA and FA profiles were quantified separately by mass spectrometry and gas chromatography. General linear models were performed to assess the differences among the groups. After adjusted for potential confounders, children with NAFLD had higher levels of chenodeoxycholic acid (CDCA), unconjugated primary BAs (CDCA + cholic acid) but lower levels of deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), glycodeoxycholic acid (GDCA), total DCA (DCA + TDCA + GDCA), glycolithocholic acid (GLCA) and total lithocholic acid (GLCA + taurolithocholic acid) than children without NAFLD. As for FAs, children with mild and moderate to severe NAFLD had higher levels of n-7 monounsaturated FA. Circulating BA and FA profiles may change in children with NAFLD. Further studies are needed to determine their associations and to understand the underlying mechanism of action. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Non-alcoholic fatty liver disease: An expanded review

PubMed Central

Benedict, Mark; Zhang, Xuchen

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the “magic bullet” in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients. PMID:28652891

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

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.

Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

PubMed Central

Manti, Sara; Romano, Claudio; Chirico, Valeria; Filippelli, Martina; Cuppari, Caterina; Loddo, Italia; Salpietro, Carmelo; Arrigo, Teresa

2014-01-01

Context: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". Results: NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. Conclusions: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH. PMID:24829591

Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease.

PubMed

Haas, Joel T; Francque, Sven; Staels, Bart

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterized by abnormal hepatic fat accumulation, inflammation, and hepatocyte dysfunction. Importantly, it is also closely linked to obesity and the metabolic syndrome. NAFLD predisposes susceptible individuals to cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Although the precise signals remain poorly understood, NAFLD pathogenesis likely involves actions of the different hepatic cell types and multiple extrahepatic signals. The complexity of this disease has been a major impediment to the development of appropriate metrics of its progression and effective therapies. Recent clinical data place increasing importance on identifying fibrosis, as it is a strong indicator of hepatic disease-related mortality. Preclinical modeling of the fibrotic process remains challenging, particularly in the contexts of obesity and the metabolic syndrome. Future studies are needed to define the molecular pathways determining the natural progression of NAFLD, including key determinants of fibrosis and disease-related outcomes. This review covers the evolving concepts of NAFLD from both human and animal studies. We discuss recent clinical and diagnostic methods assessing NAFLD diagnosis, progression, and outcomes; compare the features of genetic and dietary animal models of NAFLD; and highlight pharmacological approaches for disease treatment.

An update on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Asia.

PubMed

Hsu, Ching-Sheng; Kao, Jia-Horng

2017-08-01

Non-alcoholic fatty liver disease (NAFLD) has become the most overwhelming liver disease in Asia. In consideration of its increasing medical and economic impact on Asian people, it is time for us to review the update data in Asian countries and formulate strategies to cope with this emerging health problem in Asia. Moreover, growing data indicates that NAFLD may be a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with several extra-hepatic manifestations, such as cardiovascular diseases, chronic renal diseases, and malignancy. As the co-occurrence of NAFLD and viral hepatitis is common in Asia, issues related to the impact of NAFLD on the clinical outcomes and management of viral hepatitis remain to be elucidated. Areas covered: In this article, a narrative review was conducted, searching for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database till August 2016. Studies relevant to the emerging data of NAFLD in Asia, including the diagnosis, risk factors, the assessment and management of Asian NAFLD patients were examined and discussed. Expert commentary: Collaboration in Asian countries to develop an effective and practical measurement to assess the severity of NAFLD is urgently required.

Effects of sulfate chitosan derivatives on nonalcoholic fatty liver disease

NASA Astrophysics Data System (ADS)

Yu, Mingming; Wang, Yuanhong; Jiang, Tingfu; Lv, Zhihua

2014-06-01

Sulfate chitosan derivatives have good solubility and therapeutic effect on the cell model of NAFLD. The aim of this study was to examine the therapeutic effect of sulfate chitosan derivatives on NAFLD. The male Wistar rats were orally fed high fat emulsion and received sulfate chitosan derivatives for 5 weeks to determine the pre-treatment effect of sulfate chitosan derivatives on NAFLD. To evaluate the therapeutic effect of sulfate chitosan derivatives on NAFLD, the rats were orally fed with high concentration emulsion for 5 weeks, followed by sulfate chitosan derivatives for 3 weeks. Histological analysis and biomedical assays showed that sulfate chitosan derivatives can dramatically prevent the development of hepatic steatosis in hepatocyte cells. In animal studies, pre-treatment and treatment with sulfate chitosan derivatives significantly protected against hepatic steatohepatitis induced by high fat diet according to histological analysis. Furthermore, increased TC, ALT, MDA, and LEP in NAFLD were significantly ameliorated by pre-treatment and treatment with sulfate chitosan derivatives. Furthermore, increased TG, AST, and TNF-α in NAFLD were significantly ameliorated by treatment with sulfate chitosan derivatives. Sulfate chitosan derivatives have good pre-treatment and therapeutic effect on NAFLD.

Gut-Liver Axis, Nutrition, and Non Alcoholic Fatty Liver Disease

PubMed Central

Kirpich, Irina A.; Marsano, Luis S.; McClain, Craig J.

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called ”gut-liver axis”, play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host’s metabolism contributing to NAFLD development. PMID:26151226

Valproic acid and nonalcoholic fatty liver disease: A possible association?

PubMed Central

Farinelli, Edoardo; Giampaoli, David; Cenciarini, Anja; Cercado, Ephraim; Verrotti, Alberto

2015-01-01

Valproic acid (VPA) is one of the most prescribed drugs in children with newly diagnosed epilepsy. Weight gain and obesity have been observed as side effects of VPA. These are often linked with other metabolic disturbances such as development of insulin resistance, dyslipidemia, metabolic syndrome (MetS) and non-alcoholic fatty liver disease or nonalcoholic fatty liver disease (NAFLD). NAFLD refers to a group of liver disorders with marked hepatic steatosis. It is associated with an increased incidence of cardiovascular diseases and overall reduced life expectancy. NAFLD occurs in 20%-25% of the general population and it is known to be the most common cause of chronic liver disease. NAFLD therefore represents a major public health issue worldwide. This study reviews and summarizes relevant literature that supports the existence of an association between VPA therapy and the development of NAFLD in children. Long-term VPA-therapy appears to be associated with an increased risk of developing NAFLD. Further studies are needed to clarify the pathogenic mechanisms that lie behind this association and to standardize the options for the use of this drug in overweight patients and in those with risks for developing MetS and NAFLD. PMID:26019740

Epigenetic Mechanisms Underlying the Link between Non-Alcoholic Fatty Liver Diseases and Nutrition

PubMed Central

Lee, Joo Ho; Friso, Simonetta; Choi, Sang-Woon

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is defined as a pathologic accumulation of fat in the form of triglycerides (TG) in the liver (steatosis) that is not caused by alcohol. A subgroup of NAFLD patients shows liver cell injury and inflammation coupled with the excessive fat accumulation (steatohepatitis), which is referred to as non-alcoholic steatohepatitis (NASH). Patients with NASH may develop cirrhosis and hepatocellular carcinoma (HCC). NAFLD shares the key features of metabolic syndrome including obesity, hyperlipidemia, hypertension, and insulin resistance. The pathogenesis of NAFLD is multi-factorial, however the oxidative stress seems to plays a major role in the development and progression of the disease. The emerging field of epigenetics provides a new perspective on the pathogenesis of NAFLD. Epigenetics is an inheritable but reversible phenomenon that affects gene expression without altering the DNA sequence and refers to DNA methylation, histone modifications and microRNAs. Epigenetic manipulation through metabolic pathways such as one-carbon metabolism has been proposed as a promising approach to retard the progression of NAFLD. Investigating the epigenetic modifiers in NAFLD may also lead to the development of preventive or therapeutic strategies for NASH-associated complications. PMID:25195642

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.

Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases.

PubMed

Han, Eugene; Lee, Yong Ho

2017-12-01

As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged. Copyright © 2017 Korean Diabetes Association.

Topical Treatment With an Agent Disruptive to <em>P. acnesem> Biofilm Provides Positive Therapeutic Response: Results of a Randomized Clinical Trial.

PubMed

Bernhardt, Michael J; Myntti, Matthew F

2016-06-01

The traditional disease model of acne has been one of follicular plugging due to 'sticky epithelial cells' associated with increased sebum production with deep follicular anaerobic conditions favoring <em>P. acnesem>- generated inflammation. <em>P. acnesem> biofilms have been found more frequently in patients with acne than controls. Biofilms are genetically coded to create adhesion to the pilosebaceous unit followed by production of a mucopolysaccharide coating capable of binding to lipid surfaces. Traditional therapies for acne have involved mixtures of oral and topical antibiotics admixed with topical keratolytics and retinoids, which are aimed at traditional bacterial reduction as well as downregulating the inflammatory cascade. These approaches are limited by side effect and compliance/tolerability issues. As the <em>P. acnesem> biofilm may, in fact, be the instigator of this process, we studied the use of a topical agent designed to reduce the <em>P. acnesem> biofilm to see if reducing the biofilm would be therapeutically efficacious. We present data of a proprietary topical non-prescription agent with a novel pharmaco mechanism designed to attack the biofilm produced by <em>P. acnesem>. Our data shows a decrease of inflammatory lesions by 44% and non-inflammatory lesions by 32% after 12 weeks and also provided for a meaningful improvement in the quality of life of the patients in the study. These improvements were achieved with a product that was not associated with burning, chafing, irritation, or erythema, which can be seen with topical treatments. It is apparent from this study that by addressing the biofilm which protects the <em>P. acnesem> bacteria through the use of the Acne Gel, the incidence of acne symptoms can be greatly reduced, while having no negative impacts on the patients' skin (ClinicalTrials.gov registry number NCT02404285).

<em>J Drugs Dermatol. em>2016;15(6):677-683.

Estudo em microondas do aprisionamento e precipitação de elétrons em explosões solares

NASA Astrophysics Data System (ADS)

Rosal, A. C.; Costa, J. E. R.

2003-08-01

Uma explosão solar é uma variação rápida e intensa do brilho que ocorre nas chamadas regiões ativas da atmosfera, constituídas por um plasma magnetizado com intensa indução magnética. Os modelos de explosões solares atuais, discutidos na literatura, apresentam características de aprisionamento e precipitação de elétrons em ambientes magnéticos simplificados. Neste trabalho, nos propusemos a separar a emissão dos elétrons aprisionados da emissão dos elétrons em precipitação apenas a partir da emissão em microondas, melhorando portanto o controle sobre o conjunto de parâmetros inferidos. A emissão em microondas da população em precipitação é bastante fraca e portanto da nossa base de dados de 130 explosões observadas pelo Rádio Polarímetro de Nobeyama, em sete freqüências, apenas para 32 foi possível separar as duas componentes de emissão com uma boa razão sinal/ruído. A partir de estudos das escalas de tempo das emissões devidas à variação gradual da emissão no aprisionamento e da variação rápida da emissão dos elétrons em precipitação foi possível obter a separação utilizando um filtro temporal nas emissões resultantes. Em nossa análise destas explosões estudamos os espectros girossincrotrônicos da emissão gradual, a qual associamos provir do topo dos arcos magnéticos e da emissão de variação rápida associada aos elétrons em precipitação. Estes espectros foram calculados e dos quais inferimos que a indução magnética efetiva do topo e dos pés foi em média, Btopo = 236 G e Bpés = 577 G, inferidas das freqüências de pico dos espectros em ntopo = 11,8 GHz e npés = 14,6 GHz com leve anisotropia (pequeno alargamento espectral). O índice espectral da distribuição não-térmica de elétrons d, inferido do índice espectral de fótons da emissão em regime opticamente fino, foi de dtopo = 3,3 e dpés = 3,9. Estes parâmetros são típicos da maioria das análises realizadas em ambiente único de

Obstructive sleep apnea syndrome and fatty liver: Association or causal link?

PubMed Central

Ahmed, Mohamed H; Byrne, Christopher D

2010-01-01

Obstructive sleep apnea (OSA) is a complex disorder that consists of upper airway obstruction, chronic intermittent hypoxia and sleep fragmentation. OSA is well known to be associated with hypoxia, insulin resistance and glucose intolerance, and these factors can occur in the presence or absence of obesity and metabolic syndrome. Although it is well established that insulin resistance, glucose intolerance and obesity occur frequently with non-alcoholic fatty liver disease (NAFLD), it is now becoming apparent that hypoxia might also be important in the development of NAFLD, and it is recognized that there is increased risk of NAFLD with OSA. This review discusses the association between OSA, NAFLD and cardiovascular disease, and describes the potential role of hypoxia in the development of NAFLD with OSA. PMID:20818807

Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: Consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology

PubMed Central

Gao, Xin; Fan, Jian-Gao

2013-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, affecting 20%–33% of the general population. Large population-based surveys in China indicate a prevalence of approximately 15%–30%. Worldwide, including in China, the prevalence of NAFLD has increased rapidly in parallel with regional trends of obesity, type2 diabetes and metabolic syndrome. In addition, NAFLD has contributed significantly to increased overall, as well as cardiovascular and liver-related, mortality in the general population. In view of rapid advances in research into NAFLD in recent years, this consensus statement provides a brief update on the progress in the field and suggests preferred approaches for the comprehensive management of NAFLD and its related metabolic diseases. PMID:23560695

Relationship between obstructive sleep apnea and nonalcoholic fatty liver disease in nonobese adults.

PubMed

Qi, Jia-Chao; Huang, Jian-Chai; Lin, Qi-Chang; Zhao, Jian-Ming; Lin, Xin; Chen, Li-Da; Huang, Jie-Feng; Chen, Xiao

2016-05-01

Obstructive sleep apnea (OSA) is closely related to nonalcoholic fatty liver disease (NAFLD), though the mechanism is not conclusive as obesity is a confounder. The objective of this observational study was to investigate the correlation between these disorders in nonobese subjects. We consecutively enrolled nonobese individuals undergoing polysomnography and abdominal ultrasonography and analyzed differences in NAFLD patients grouped by the apnea-hypopnea index (AHI) and in OSA patients according to the presence or absence of NAFLD. Multivariate regression analysis was used to evaluate the independent risks of NAFLD in OSA patients. A total of 175 participants were included. The 106 ultrasound-diagnosed NAFLD patients were classified into four groups by AHI. There were no significant differences in triglycerides (TG), serum aminotransferase levels of alanine aminotransferase and aspartate aminotransferase, high-sensitivity C-reactive protein, and homeostasis model assessment of insulin resistance (HOMA-IR) with worsening OSA. In both OSA patients with NAFLD and those without NAFLD, body mass index (BMI), the lowest oxygen saturation (LaSO2), HOMA-IR, and TG were significantly associated. Additionally, BMI, LaSO2, and TG independently predicted the development of NAFLD after adjustments (odds ratio [OR] = 1.562, p = 0.003; OR = 0.960, p = 0.03; OR = 3.410, p < 0.001, respectively). In nonobese subjects, OSA itself does not appear to induce significant changes in liver enzymes. With reference to lipid metabolism, weight control and OSA-related hypoxemia are key factors in reducing the risk of NAFLD in OSA patients. Additional large-scale, prospective studies are warranted to investigate the impact of OSA on liver injury in nonobese adults.

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.

Biochemical Predictors of Early Onset Non-Alcoholic Fatty Liver Disease in Young Children with Obesity.

PubMed

Kim, Ju Young; Cho, Jinmin; Yang, Hye Ran

2018-04-16

The prevalence of metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) and their associated risk factors are not well-established in young children with obesity. The purpose of this study was to evaluate the prevalence of early onset NAFLD and identify its biochemical predictors in obese children aged less than 10 years. Anthropometric measurements, blood pressure, laboratory tests, and abdominal ultrasonography (USG) were performed in all subjects. National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria for MS diagnosis and liver enzymes and USG for NAFLD diagnosis were assessed. A total of 356 children with obesity (233 boys, 123 girls) were included, with 172 children age ≤ 10 years and 184 adolescents. The prevalence of MS was 23.3% in young children and 35.3% in adolescents (P = 0.020); while the prevalence of NAFLD was 36.0% and 70.7%, respectively (P = 0.001). In obese children aged 10 years or less, there were significant differences in levels of serum γ-glutamyltranspeptidase (γGT) (P < 0.001), triglycerides (P = 0.042), and homeostatic model assessment of insulin resistance (P < 0.001) between the non-NAFLD and the NAFLD group. Multivariate logistic regression analysis revealed significant increase in serum γGT and uric acid levels in young children. Although MS and NAFLD were more prevalent in adolescents, young children also demonstrated MS and NAFLD as obesity-related complications. Elevated serum γGT and uric acid levels may serve as biochemical predictors in detecting NAFLD in young children with obesity before investigation with abdominal USG. © 2018 The Korean Academy of Medical Sciences.

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.

Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease

PubMed Central

Schwimmer, J B; Newton, K P; Awai, H I; Choi, L J; Garcia, M A; Ellis, L L; Vanderwall, K; Fontanesi, J

2013-01-01

Background Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. Aim To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. Methods Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. Results Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. Conclusions Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner. PMID:24117728

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.

Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease.

PubMed

Schwimmer, J B; Newton, K P; Awai, H I; Choi, L J; Garcia, M A; Ellis, L L; Vanderwall, K; Fontanesi, J

2013-11-01

Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner. © 2013 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Could inherited predisposition drive non-obese fatty liver disease? Results from German tertiary referral centers.

PubMed

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

2018-05-01

Non-alcoholic fatty liver disease (NAFLD) is frequent among obese individuals with metabolic syndrome. Variants PNPLA3 p.I148M, TM6SF2 p.E167K and MBOAT7 rs641738 are associated with higher liver fat contents. Here we analyzed 63 biopsied non-obese, non-diabetic patients with NAFLD (39 men, age: 20-72 years) recruited within the German NAFLD CSG program. The frequencies of the PNPLA3, TM6SF2 and MBOAT7 polymorphisms were compared with the remaining patients in the NAFLD CSG cohort and with a control population (n = 174). Serum CK18-M30 was measured by ELISA. In non-obese NAFLD patients, the frequency of the PNPLA3 p.I148M allele (74.6%), but not of the TM6SF2 or MBOAT7 polymorphisms, was significantly (P < 0.05) higher as compared to the other patients in the NAFLD CSG cohort (54.9%) or controls (40.2%). The presence of the minor PNPLA3 p.I148M risk allele increased the risk of developing NAFLD (OR = 3.29, P < 0.001) and was associated with higher steatosis, fibrosis, and serum CK18-M30 levels (all P < 0.05). According to the population attributable fraction (PAF), 49.8% of NAFLD cases could be eliminated if the PNPLA3 mutation was absent. The MBOAT7 polymorphism was more frequent (P = 0.019) in patients with severe hepatic steatosis. In conclusion, PNPLA3, and to a lesser extent, MBOAT7 variants are associated with NAFLD risk and modulate liver injury in non-obese patients without diabetes.

Temporal Trends of Non-alcoholic Fatty Liver Disease-related Hepatocellular Carcinoma in the Veteran Affairs Population

PubMed Central

Mittal, Sahil; Sada, Yvonne H.; El-Serag, Hashem B.; Kanwal, Fasiha; Duan, Zhigang; Temple, Sarah; May, Sarah B.; Kramer, Jennifer R.; Richardson, Peter A.; Davila, Jessica A.

2014-01-01

Background & Aims Non-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, no systemic studies from the United States have examined temporal trends, HCC surveillance practices, and outcomes of NAFLD-related HCC. Methods We identified a national cohort of 1500 patients who developed HCC from 2005 through 2010 from Veterans Administration (VA) hospitals. We reviewed patients’ full VA medical records; NAFLD was diagnosed based on histologic evidence for, or the presence of, metabolic syndrome in the absence of hepatitis C virus (HCV) infection, hepatitis B, or alcoholic liver disease. We compared annual prevalence values for the main risk factors (NAFLD, alcohol abuse, HCV), as well HCC surveillance and outcomes, among HCC patients. Results NAFLD was the underlying risk factor for HCC in 120 patients (8.0%); the annual proportion of NAFLD-related HCC remained relatively stable (7.5%–12.0%). In contrast, the proportion of HCC cases associated with HCV increased from 61.0% in 2005 (95% confidence interval, 53.1%–68.9%) to 74.9% in 2010 (95% confidence interval, 69.0%–80.7%). The proportion of HCC cases associated with only alcohol abuse decreased from 21.9% in 2005 to 15.7% in 2010, and the annual proportion of HCC cases associated with hepatitis B remained relatively stable (1.4%–3.5%). A significantly lower proportion of patients with NAFLD-related HCC had cirrhosis (58.3%) compared to patients with alcohol- or HCV-related HCC (72.4% and 85.6%, respectively; P<.05). A significantly higher percentage of patients with NAFLD-related HCC did not receive HCC surveillance in the 3 years before their HCC diagnosis, compared to patients with alcohol- or HCV-associated HCC. A lower proportion of patients with NAFLD-related HCC received HCC-specific treatment (61.5%) than of patients with HCV-related HCC (77.5%; P<.01). However, 1-year survival did not differ among patients with HCC related to different risk factors

Retrospectively exploring the importance of items in the decision to leave the emergency medical services (EMS) profession and their relationships to life satisfaction after leaving EMS and likelihood of returning to EMS.

PubMed

Blau, Gary; Chapman, Susan

2011-01-01

An exit survey was returned by a sample of 127 respondents in fully compensated positions who left the EMS profession, most within 12 months prior to filling out the exit survey. A very high percentage continued to work after leaving EMS. Respondents were asked to rate the importance of each of 17 items in affecting their decision to leave EMS. A higher than anticipated response to a "not applicable" response choice affected the usability of 8 of these items. Nine of the 17 items had at least 65 useable responses and were used for further analysis. Within these 9, stress/burnout and lack of job challenges had the highest importance in affecting the decision to leave EMS, while desire for better pay and benefits had the lowest importance. Desire for career change was positively related to life satisfaction after leaving EMS and negatively related to likelihood of returning to EMS. Stress/burnout was positively related to life satisfaction after leaving EMS. Study limitations and future research issues are briefly discussed.

Prevalence and risk factors of nonalcoholic fatty liver disease in breast cancer patients.

PubMed

Lee, Seokwon; Jung, Younglae; Bae, Youngtae; Yun, Sung Pil; Kim, Suk; Jo, Hongjae; Seo, Hyung-Il

2017-03-24

We aimed to evaluate the prevalence of nonalcoholic fatty liver disease (NAFLD) in breast cancer patients using liver magnetic resonance imaging (MRI), and to investigate factors associated with NAFLD. We evaluated 104 patients surgically treated for breast cancer at our hospital between September and November 2013. None of the patients had any other causes of secondary hepatic fat accumulation (such as significant alcohol consumption, use of steatogenic medication or inborn disorders). Hepatic fat accumulation was measured using liver MRI perfomed in all patients before surgical treatment. Based on the fat signal percentage from liver MRIs, 19 of 104 breast cancer patients were diagnosed with NAFLD, so the prevalence of NAFLD was 18.3%. In univariate analysis, factors associated with NAFLD were older age, high body mass index, type 2 diabetes mellitus (DM), hypertension, elevated aspartate aminotransferase, elevated alanine aminotransferase and elevated triglycerides (TG). In multivariate analysis, factors associated with NAFLD were high body mass index (BMI) (odds ratio [OR] 1.403; 95% confidence interval [CI] 1.111-1.771; p = 0.005), type 2 DM (OR 11.872; 95% CI 1.065-132.373; p = 0.044), and an elevated TG level (OR 50.267; 95% CI 4.409-573.030; p = 0.002). The prevalence of NAFLD in breast cancer patients was not different from that of the general population. High BMI, type 2 DM and an elevated serum TG level were factors associated with NAFLD.

Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease

PubMed Central

Dong, Shu; Zhan, Zong-Ying; Cao, Hong-Yan; Wu, Chao; Bian, Yan-Qin; Li, Jian-Yuan; Cheng, Gen-Hong; Liu, Ping; Sun, Ming-Yu

2017-01-01

AIM To identify a panel of biomarkers that can distinguish between non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and explore molecular mechanism involved in the process of developing NASH from NAFLD. METHODS Biomarkers may differ during stages of NAFLD. Urine and blood were obtained from non-diabetic subjects with NAFLD and steatosis, with normal liver function (n = 33), from patients with NASH, with abnormal liver function (n = 45), and from healthy age and sex-matched controls (n = 30). Samples were subjected to metabolomic analysis to identify potential non-invasive biomarkers. Differences in urinary metabolic profiles were analyzed using liquid chromatography tandem mass spectrometry with principal component analysis and partial least squares-discriminate analysis. RESULTS Compared with NAFLD patients, patients with NASH had abnormal liver function and high serum lipid concentrations. Urinary metabonomics found differences in 31 metabolites between these two groups, including differences in nucleic acids and amino acids. Pathway analysis based on overlapping metabolites showed that pathways of energy and amino acid metabolism, as well as the pentose phosphate pathway, were closely associated with pathological processes in NAFLD and NASH. CONCLUSION These findings suggested that a panel of biomarkers could distinguish between NAFLD and NASH, and could help to determine the molecular mechanism involved in the process of developing NASH from NAFLD. Urinary biomarkers may be diagnostic in these patients and could be used to assess responses to therapeutic interventions. PMID:28487615

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.

Elevated whole blood viscosity is associated with insulin resistance and non-alcoholic fatty liver.

PubMed

Zhao, Hong-yan; Li, Jing; Xu, Min; Wang, Tian-ge; Sun, Wan-wan; Chen, Ying; Bi, Yu-fang; Wang, Wei-qing; Ning, Guang

2015-12-01

Accumulating evidences demonstrate that abnormalities in whole blood viscosity (WBV) have been implicated in insulin resistance which may lead to non-alcoholic fatty liver disease (NAFLD). However, epidemiological studies exploring the association between WBV and NAFLD were not available. Our objective was to evaluate the association between WBV levels and risk of prevalent NAFLD. This was a cross-sectional population-based study performed in Shanghai, China. A total of 8673 participants aged 40 years or older were included. WBV was calculated from haematocrit and plasma protein concentration, at a shear rate of 208(-1) s, by a validated equation. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Insulin resistance (IR) was assessed by homeostasis model assessment (HOMA-IR). The overall prevalence of NAFLD was 30·2% in this population. With the increase of WBV level, participants have larger waist circumference (WC), more severe insulin resistance and the prevalence of NAFLD increased significantly with elevated WBV quartiles. Compared with those in the lowest quartiles, adults in the highest quartile of WBV levels have higher prevalence of NAFLD (adjusted odds ratio 1·77, 95% confidence interval [CI] 1·48-2·13) and IR (2·72, 95% CI 2·26-3·27). Elevated WBV is associated with prevalence of NAFLD and IR in middle-aged and elderly Chinese population. © 2015 John Wiley & Sons Ltd.

Non alcoholic fatty liver disease in a Nigerian population with type II diabetes mellitus.

PubMed

Olusanya, Titilola Osawaye; Lesi, Olufunmilayo Adenike; Adeyomoye, Adekunle Ayokunle; Fasanmade, Olufemi Adetola

2016-01-01

Worldwide, Non-alcoholic fatty liver disease (NAFLD) has become an important cause of chronic liver disease and cardiovascular morbidity, even more so in subjects with Type II Diabetes Mellitus (T2DM). The aim of this study was to determine the prevalence and risk factors of NAFLD in an African population with Type II Diabetes Mellitus. We performed a case control study and evaluated anthropometric and biochemical risk factors for NAFLD in 336 subjects (T2DM and non-diabetic controls). Parameters assessed included estimation of BMI (Body Mass Index), measurement of waist circumference (WC), serum cholesterol including HDL-C, LDL-C and triglyceride and serum transaminases (ALT and AST). Hepatitis B and C viral antibody screening was also performed. The diagnosis of NAFLD was confirmed by identification of hepatic steatosis on abdominal ultrasound scan evaluation and exclusion of significant alcohol consumption. NAFLD was identified in 16.7% (28 of 168) patients with T2DM compared with 1.2% (2 of 168) non-diabetic controls (Odds Ratio 16.6; p < 0.001). Central obesity (WC > 102cm) and dyslipidaemia (HDL-c < 40mg/dl) were independently associated with NAFLD in male subjects with T2DM (p = 0.03 and p = 0.04 respectively). NAFLD occurred more frequently in patients with T2DM than controls and was associated with central obesity and dyslipidaemia. The diabetic subjects with NAFLD will require more intensive therapy to decrease the risk of hepatic, cardiovascular and other adverse events.

Use of Mac‐2 binding protein as a biomarker for nonalcoholic fatty liver disease diagnosis

PubMed Central

Kamada, Yoshihiro; Ono, Masafumi; Hyogo, Hideyuki; Fujii, Hideki; Sumida, Yoshio; Yamada, Makoto; Mori, Kojiroh; Tanaka, Saiyu; Maekawa, Tomohiro; Ebisutani, Yusuke; Yamamoto, Akiko; Takamatsu, Shinji; Yoneda, Masashi; Kawada, Norifumi; Chayama, Kazuaki; Saibara, Toshiji; Takehara, Tetsuo

2017-01-01

In contrast to patients with viral hepatitis, patients with nonalcoholic fatty liver disease (NAFLD) can progress to hepatocellular carcinoma during the initial stages of liver fibrosis. Development and implementation of noninvasive methods for diagnosis and progression prediction are important for effective NAFLD surveillance. Mac‐2 binding protein (Mac‐2bp) is a useful nonalcoholic steatohepatitis (NASH) diagnosis biomarker and a powerful prediction biomarker for NAFLD fibrosis stage. Wisteria floribunda agglutinin (WFA)‐positive Mac‐2bp (WFA+‐M2BP) is a novel serum fibrosis biomarker for chronic hepatitis C that has clinical validity. Mac‐2bp and WFA+‐M2BP are also clinical NAFLD biomarker candidates. We examined the efficacy of Mac‐2bp and WFA+‐M2BP for NAFLD assessment using patients with biopsy‐proven NAFLD (n = 510; NAFLD cohort) and subjects who received a health check‐up (n = 2,122; check‐up cohort). In the NAFLD cohort, we set the fibrosis predicting cutoff values as 1.80 (F1), 2.21 (F2), and 2.24 μg/mL (F3). In the subjects with fatty liver from the check‐up cohort (n = 1,291), the serum Mac‐2bp levels were >1.80 μg/mL in 38.6% of the subjects (n = 498), and >2.24 μg/mL in 24.6% of the subjects (n = 318). The NAFLD cohort results indicated that Mac‐2bp and WFA+‐M2BP were equally useful for NASH diagnosis. During the early stages of fibrosis (F1, F2), the increase in Mac‐2bp was statistically significant but WFA+‐M2BP did not increase. Logistic regression analysis revealed that Mac‐2bp was an independent determinant for the prediction of advanced fibrosis stage (≥F2), even when adjusted for WFA+‐M2BP. Immunohistochemical staining of Mac‐2bp revealed that hepatocytes strongly expressed Mac‐2bp in patients with NAFLD. Conclusion: Our results indicated that hepatocyte‐derived Mac‐2bp would be a useful single biomarker for NASH diagnosis and fibrosis stage prediction in patients with NAFLD. (Hepatology

Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database

PubMed Central

Kumarendran, Balachandran; O’Reilly, Michael W.; Manolopoulos, Konstantinos N.; Toulis, Konstantinos A.; Gokhale, Krishna M.; Sitch, Alice J.; Wijeyaratne, Chandrika N.; Coomarasamy, Arri

2018-01-01

Background Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver. Methods and findings We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n = 71,061) and sex hormone-binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR = 2.23, 95% CI 1.86–2.66, p < 0.001), also after adjusting for BMI or dysglycemia. Serum testosterone >3.0 nmol/L was associated with an increase in NAFLD (HR = 2.30, 95% CI 1.16–4.53, p = 0.017 for 3–3.49 nmol/L and HR = 2.40, 95% CI 1.24–4.66, p = 0.009 for >3.5 nmol/L). Mirroring this finding, SHBG <30 nmol/L was associated with increased NAFLD hazard (HR = 4.75, 95% CI 2.44–9.25, p < 0.001 for 20–29.99 nmol/L and HR = 4.98, 95% CI 2.45–10.11, p < 0.001 for <20 nmol/L). Limitations of this study include its retrospective nature, absence of detailed information on criteria used to diagnosis PCOS and NAFLD, and absence of data on laboratory assays used to measure serum androgens. Conclusions We found that women with PCOS have an increased rate of NAFLD. In addition to increased BMI and dysglycemia, androgen excess contributes to the development of NAFLD in women with PCOS. In women with PCOS-related androgen excess, systematic

Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database.

PubMed

Kumarendran, Balachandran; O'Reilly, Michael W; Manolopoulos, Konstantinos N; Toulis, Konstantinos A; Gokhale, Krishna M; Sitch, Alice J; Wijeyaratne, Chandrika N; Coomarasamy, Arri; Arlt, Wiebke; Nirantharakumar, Krishnarajah

2018-03-01

Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver. We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n = 71,061) and sex hormone-binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR = 2.23, 95% CI 1.86-2.66, p < 0.001), also after adjusting for BMI or dysglycemia. Serum testosterone >3.0 nmol/L was associated with an increase in NAFLD (HR = 2.30, 95% CI 1.16-4.53, p = 0.017 for 3-3.49 nmol/L and HR = 2.40, 95% CI 1.24-4.66, p = 0.009 for >3.5 nmol/L). Mirroring this finding, SHBG <30 nmol/L was associated with increased NAFLD hazard (HR = 4.75, 95% CI 2.44-9.25, p < 0.001 for 20-29.99 nmol/L and HR = 4.98, 95% CI 2.45-10.11, p < 0.001 for <20 nmol/L). Limitations of this study include its retrospective nature, absence of detailed information on criteria used to diagnosis PCOS and NAFLD, and absence of data on laboratory assays used to measure serum androgens. We found that women with PCOS have an increased rate of NAFLD. In addition to increased BMI and dysglycemia, androgen excess contributes to the development of NAFLD in women with PCOS. In women with PCOS-related androgen excess, systematic NAFLD screening should be considered.

Analyses of risk factors for polycystic ovary syndrome complicated with non-alcoholic fatty liver disease.

PubMed

Zhang, Jianhai; Hu, Jian; Zhang, Chunxia; Jiao, Yanni; Kong, Xiang; Wang, Wei

2018-05-01

The risk factors related to polycystic ovary syndrome (PCOS) patients complicated with non-alcoholic fatty liver disease (NAFLD) were investigated. A total of 188 PCOS patients treated in Shengli Oilfield Central Hospital (Dongying, China) from February 2014 to February 2015 were retrospectively analyzed as PCOS group, and PCOS group was further divided into NAFLD group and non-NAFLD (N-NAFLD) group according to the liver B ultrasound. In the same time-period, 65 healthy people were selected as normal control group. The differences of clinical, biochemical and metabolic indexes were compared. The levels of luteinizing hormone (LH), LH/follicle stimulating hormone (FSH), testosterone (T), free androgen index (FAI), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) index in PCOS group were higher than those in normal control group, but the sex hormone binding globulin (SHBG) level was lower than that in normal control group (P<0.05); there were no statistically significant differences in comparisons of age, body mass index (BMI), waist-hip ratio (WHR), FSH, dehydroepiandrosterone sulfate (DHEAs) and fasting blood glucose (FBG) between the two groups (P>0.05). The prevalence rate of NAFLD in PCOS group (44.68%) was significantly higher than that in control group (24.62%) (P<0.05). The proportion of NAFLD in PCOS patients in obesity group (63.51%) was significantly higher than that in non-obesity group (15.79%) (P<0.05). In PCOS group, NAFLD patients had more obvious metabolic abnormalities [high BMI, WHR, FBG, FINS, HOMA-IR index, total cholesterol (TC) and triglyceride (TG), and low high-density lipoprotein HDL and SHBG] and androgen excess compared with those in N-NAFLD patients (P<0.05). The levels of LH, LH/FSH, FINS and HOMA-IR index in PCOS group complicated with NAFLD were higher than those in control group complicated with NAFLD (P<0.05), but the differences in age, BMI, WHR, FSH and FBG levels were not statistically

The Influence of Epicardial Fat and Nonalcoholic Fatty Liver Disease on Heart Rate Recovery in Metabolic Syndrome.

PubMed

Cho, Kyoung Im; Jo, Eun Ah; Cho, Sang Hoon; Kim, Bo Hyun

2017-06-01

Epicardial adipose tissues reflecting visceral fat accumulations of the heart are associated with metabolic syndrome (MetS) and can be a predictor of other cardiometabolic diseases. It can adversely influence autonomic nervous system (ANS) of heart. Heart rate recovery (HRR) is an easy method for measuring ANS dysfunction. The purpose of this study was to determine whether epicardial fat thickness (EFT) and nonalcoholic fatty liver disease (NAFLD) are related to HRR in patients with MetS. We enrolled 772 consecutive patients from a health-screening center who underwent abdominal ultrasonography, treadmill test, and cardiac echocardiography. EFT using echocardiography and HRR by symptom-limited exercise testing was assessed. According to the presence of MetS and NAFLD, patients were classified into the four groups. In NAFLD patients, EFT was higher and HRR was lower, especially in patients with MetS and NAFLD, compared to non-MetS participants without NAFLD (MetS with NAFLD, EFT 7.5 ± 4.4 mm, HRR 31.9 ± 12.7; MetS without NAFLD, EFT 4.9 ± 3.0 mm, HRR 39.5 ± 11.1; non-MetS with NAFLD, EFT 5.9 ± 3.6 mm, HRR 36.6 ± 12.7; and non-MetS without NAFLD, EFT 4.4 ± 3.5 mm, HRR 43.4 ± 14.5, p < 0.001). Patients with severe liver steatosis (LS) showed significantly higher EFT than those with moderate LS (14.2 ± 2.0 vs. 7.5 ± 3.1 mm, P < 0.001), and EFT was positively correlated with severity of LS (r = 0.431, P < 0.001). HRR was significantly correlated with EFT (r = -0.386, P < 0.001) and severity of LS (r = -0.324, P < 0.001). EFT and NAFLD were significantly correlated with HRR in patients with MetS and they may be highly related to increased cardiovascular risk. These results suggest a cross-link among EFT, NAFLD, and cardiac autonomic dysfunction in patients with MetS.

Omic studies reveal the pathogenic lipid droplet proteins in non-alcoholic fatty liver disease.

PubMed

Zhang, Xuelin; Wang, Yang; Liu, Pingsheng

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD), the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS), genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13) may promote the development of NAFLD.

Mediterranean diet and non-alcoholic fatty liver disease: New therapeutic option around the corner?

PubMed Central

Sofi, Francesco; Casini, Alessandro

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in Western countries, being considered as the hepatic manifestation of metabolic syndrome. NAFLD has a common pathogenic background to that of metabolic syndrome, and shares many risk factors such as obesity, hypertension, insulin resistance and dyslipidemia. Although there is no currently available evidence-based established treatment for NAFLD, all the recommendations from the medical associations indicate that the most effective treatment is to reduce weight through lifestyle modifications. Diet, indeed, plays a key role in the management of NAFLD patients, as both the quantity and quality of the diet have been reported to have a beneficial role in the onset and severity of the liver disease. Among all the diets that have been proposed, a Mediterranean diet was the most effective dietary option for inducing weight loss together with beneficial effects on all the risk factors associated with metabolic syndrome and NAFLD. Over the last few years, research has demonstrated a beneficial effect of a Mediterranean diet in NAFLD. In this review, we will examine all the available data on the association between diet, nutrients and the Mediterranean diet in association with onset and severity of NAFLD. PMID:24966604

The Natural Course of Non-Alcoholic Fatty Liver Disease

PubMed Central

Calzadilla Bertot, Luis; Adams, Leon Anton

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death. PMID:27213358

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease.

PubMed

Targher, Giovanni; Byrne, Christopher D

2017-05-01

Non-alcoholic fatty liver disease (NAFLD) is caused by an accumulation of fat in the liver; the condition can progress over time to increase the risk of developing cirrhosis, end-stage liver disease and hepatocellular carcinoma. The prevalence of NAFLD is increasing rapidly owing to the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and NAFLD has been predicted to become the most important indication for liver transplantation over the next decade. It is now increasingly clear that NAFLD not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including T2DM, cardiovascular disease and chronic kidney disease (CKD), which have a considerable impact on health-care resources. Accumulating evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and releases a variety of proinflammatory factors, prothrombotic factors and profibrogenic molecules that can promote vascular and renal damage. Furthermore, communication or 'crosstalk' between affected organs or tissues in these diseases has the potential to further harm function and worsen patient outcomes, and increasing amounts of evidence point to a strong association between NAFLD and CKD. Whether a causal relationship between NAFLD and CKD exists remains to be definitively established.

Association between Serum Uric Acid and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis.

PubMed

Darmawan, Guntur; Hamijoyo, Laniyati; Hasan, Irsan

2017-04-01

non-alcoholic fatty liver disease (NAFLD) is known to be associated with some metabolic disorders. Recent studies suggested the role of uric acid in NAFLD through oxidative stress and inflammatory process. This study is aimed to evaluate the association between serum uric acid and NAFLD. a systematic literature review was conducted using Pubmed and Cochrane library. The quality of all studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). All data were analyzed using REVIEW MANAGER 5.3. eleven studies from America and Asia involving 100,275 subjects were included. The pooled adjusted OR for NAFLD was 1.92 (95% CI: 1.66-2.23; p<0.00001). Subgroup analyses were done based on study design, gender, non-diabetic subjects, non-obese subjects. All subgroup analyses showed statistically significant adjusted OR and most of which having low to moderate heterogeneity. Two studies revealed relationship between increased serum uric acid levels and severity of NAFLD. No publication bias was observed. our study demonstrated association between serum uric acid level and NAFLD. This finding brings a new insight of uric acid in clinical practice. Increased in serum uric acid levels might serve as a trigger for physician to screen for NAFLD.

Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

PubMed

Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

2016-09-14

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease

PubMed Central

Jiang, Weiwei; Wu, Na; Wang, Xuemei; Chi, Yujing; Zhang, Yuanyuan; Qiu, Xinyun; Hu, Ying; Li, Jing; Liu, Yulan

2015-01-01

Non-alcoholic fatty liver disease (NAFLD) has recently been considered to be under the influence of the gut microbiota, which might exert toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. In this study, the composition of the gut microbiota in NAFLD patients and healthy subjects was determined via 16S ribosomal RNA Illumina next-generation sequencing. Among those taxa displaying greater than 0.1% average abundance in all samples, five genera, including Alistipes and Prevotella, were significantly more abundant in the gut microbiota of healthy subjects compared to NAFLD patients. Alternatively, Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in the gut microbiota of NAFLD patients compared to healthy subjects. In addition, decreased numbers of CD4+ and CD8+ T lymphocytes and increased levels of TNF-α, IL-6 and IFN-γ were detected in the NAFLD group compared to the healthy group. Furthermore, irregularly arranged microvilli and widened tight junctions were observed in the gut mucosa of the NAFLD patients via transmission electron microscopy. We postulate that aside from dysbiosis of the gut microbiota, gut microbiota-mediated inflammation of the intestinal mucosa and the related impairment in mucosal immune function play an important role in the pathogenesis of NAFLD. PMID:25644696

Insulin resistance, body composition, and fat distribution in obese children with nonalcoholic fatty liver disease.

PubMed

Yang, Hye Ran; Chang, Eun Jae

2016-01-01

The aim of this study was to evaluate the influence of body composition, especially distribution of body fat, and insulin resistance on nonalcoholic fatty liver disease (NAFLD) in obese children. One hundred obese children (66 boys, 34 girls) with (n=60) and without NAFLD (n=40) were assessed. Anthropometry, laboratory tests, abdominal ultrasonography, and dual energy x-ray absorption metry (DXA) were evaluated in all subjects. Subject age and measurements of liver enzymes, γ- glutamyl transpeptidase (γGT), uric acid, high-density lipoprotein cholesterol, and insulin resistance were significantly different between the non-NAFLD group and NAFLD group. Body fat and trunk fat percentage were significantly different between the two groups (p<0.001 and p=0.003), whereas extremity fat percentage was not (p=0.683). Insulin resistance correlated significantly with body fat and trunk fat percentages, age, liver enzymes, γGT, and uric acid in obese children. Multiple logistic regression analysis indicated that insulin resistance and trunk fat percentage significantly affected the development of NAFLD in obese children. Body fat, especially abdominal fat, influences the development of insulin resistance and subsequent NAFLD in obese children. Therefore, body composition measurement using DXA, in conjunction with biochemical tests, may be beneficial in evaluating obese children with NAFLD.

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

Nutritional Approaches to Achieve Weight Loss in Nonalcoholic Fatty Liver Disease123

PubMed Central

Hsu, Christine C; Ness, Erik; Kowdley, Kris V

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5–10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches to Stop Hypertension diet, a sodium-restricted diet, has been associated with less prevalence of NAFLD and has been shown to improve NAFLD. In addition, the Mediterranean diet has been promising in improving hepatic steatosis, and a larger randomized controlled trial is currently enrolling subjects. For those who are unable to pursue weight loss through dietary approaches, bariatric surgery has been shown to improve hepatic steatosis and steatohepatitis. This method has been variable in improving hepatic fibrosis. In conclusion, weight loss is crucial to the improvement of NAFLD and NASH, and patients should attempt various diets in an attempt to achieve weight loss. PMID:28298270

Capybara Oil Improves Hepatic Mitochondrial Dysfunction, Steatosis, and Inflammation in a Murine Model of Nonalcoholic Fatty Liver Disease.

PubMed

Marinho, Polyana C; Vieira, Aline B; Pereira, Priscila G; Rabelo, Kíssila; Ciambarella, Bianca T; Nascimento, Ana L R; Cortez, Erika; Moura, Aníbal S; Guimarães, Fernanda V; Martins, Marco A; Barquero, Gonzalo; Ferreira, Rodrigo N; de Carvalho, Jorge J

2018-01-01

Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of liver dysfunction worldwide and is commonly associated with obesity. Evidences suggest that NAFLD might be a mitochondrial disease, which contributes to the hepatic steatosis, oxidative stress, cytokine release, and cell death. Capybara oil (CO) is a rich source of polyunsaturated fatty acids (PUFA), which is known to improve inflammation and oxidative stress. In order to determine the effects of CO on NAFLD, C57Bl/6 mice were divided into 3 groups and fed a high-fat diet (HFD) (NAFLD group and NAFLD + CO group) or a control diet (CG group) during 16 weeks. The CO (1.5 g/kg/daily) was administered by gavage during the last 4 weeks of the diet protocol. We evaluated plasma liver enzymes, hepatic steatosis, and cytokine expression in liver as well as hepatocyte ultrastructural morphology and mitochondrial function. CO treatment suppressed hepatic steatosis, attenuated inflammatory response, and decreased plasma alanine aminotransferase (ALT) in mice with NAFLD. CO was also capable of restoring mitochondrial ultrastructure and function as well as balance superoxide dismutase and catalase levels. Our findings indicate that CO treatment has positive effects on NAFLD improving mitochondrial dysfunction, steatosis, acute inflammation, and oxidative stress.

Nutritional Approaches to Achieve Weight Loss in Nonalcoholic Fatty Liver Disease.

PubMed

Hsu, Christine C; Ness, Erik; Kowdley, Kris V

2017-03-01

Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches to Stop Hypertension diet, a sodium-restricted diet, has been associated with less prevalence of NAFLD and has been shown to improve NAFLD. In addition, the Mediterranean diet has been promising in improving hepatic steatosis, and a larger randomized controlled trial is currently enrolling subjects. For those who are unable to pursue weight loss through dietary approaches, bariatric surgery has been shown to improve hepatic steatosis and steatohepatitis. This method has been variable in improving hepatic fibrosis. In conclusion, weight loss is crucial to the improvement of NAFLD and NASH, and patients should attempt various diets in an attempt to achieve weight loss. © 2017 American Society for Nutrition.

Dietary habits and behaviors associated with nonalcoholic fatty liver disease

PubMed Central

Yasutake, Kenichiro; Kohjima, Motoyuki; Kotoh, Kazuhiro; Nakashima, Manabu; Nakamuta, Makoto; Enjoji, Munechika

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of health problems in Western (industrialized) countries. Moreover, the incidence of infantile NAFLD is increasing, with some of these patients progressing to nonalcoholic steatohepatitis. These trends depend on dietary habits and life-style. In particular, overeating and its associated obesity affect the development of NAFLD. Nutritional problems in patients with NAFLD include excess intake of energy, carbohydrates, and lipids, and shortages of polyunsaturated fatty acids, vitamins, and minerals. Although nutritional therapeutic approaches are required for prophylaxis and treatment of NAFLD, continuous nutrition therapy is difficult for many patients because of their dietary habits and lifestyle, and because the motivation for treatment differs among patients. Thus, it is necessary to assess the nutritional background and to identify nutritional problems in each patient with NAFLD. When assessing dietary habits, it is important to individually evaluate those that are consumed excessively or insufficiently, as well as inappropriate eating behaviors. Successful nutrition therapy requires patient education, based on assessments of individual nutrients, and continuing the treatment. In this article, we update knowledge about NAFLD, review the important aspects of nutritional assessment targeting treatment success, and present some concrete nutritional care plans which can be applied generally. PMID:24587653

Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance.

PubMed

Da Silva, Hannah E; Teterina, Anastasia; Comelli, Elena M; Taibi, Amel; Arendt, Bianca M; Fischer, Sandra E; Lou, Wendy; Allard, Johane P

2018-01-23

This study aimed to determine if there is an association between dysbiosis and nonalcoholic fatty liver disease (NAFLD) independent of obesity and insulin resistance (IR). This is a prospective cross-sectional study assessing the intestinal microbiome (IM) of 39 adults with biopsy-proven NAFLD (15 simple steatosis [SS]; 24 nonalcoholic steatohepatitis [NASH]) and 28 healthy controls (HC). IM composition (llumina MiSeq Platform) in NAFLD patients compared to HC were identified by two statistical methods (Metastats, Wilcoxon). Selected taxa was validated using quantitative PCR (qPCR). Metabolites in feces and serum were also analyzed. In NAFLD, 8 operational taxonomic units, 6 genera, 6 families and 2 phyla (Bacteroidetes, Firmicutes) were less abundant and; 1 genus (Lactobacillus) and 1 family (Lactobacillaceae) were more abundant compared to HC. Lower abundance in both NASH and SS patients compared to HC were confirmed by qPCR for Ruminococcus, Faecalibacterium prausnitzii and Coprococcus. No difference was found between NASH and SS. This lower abundance in NAFLD (NASH+SS) was independent of BMI and IR. NAFLD patients had higher concentrations of fecal propionate and isobutyric acid and serum 2-hydroxybutyrate and L-lactic acid. These findings suggest a potential role for a specific IM community and functional profile in the pathogenesis of NAFLD.

Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease

PubMed Central

Jiang, Changtao; Xie, Cen; Li, Fei; Zhang, Limin; Nichols, Robert G.; Krausz, Kristopher W.; Cai, Jingwei; Qi, Yunpeng; Fang, Zhong-Ze; Takahashi, Shogo; Tanaka, Naoki; Desai, Dhimant; Amin, Shantu G.; Albert, Istvan; Patterson, Andrew D.; Gonzalez, Frank J.

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is a major worldwide health problem. Recent studies suggest that the gut microbiota influences NAFLD pathogenesis. Here, a murine model of high-fat diet–induced (HFD-induced) NAFLD was used, and the effects of alterations in the gut microbiota on NAFLD were determined. Mice treated with antibiotics or tempol exhibited altered bile acid composition, with a notable increase in conjugated bile acid metabolites that inhibited intestinal farnesoid X receptor (FXR) signaling. Compared with control mice, animals with intestine-specific Fxr disruption had reduced hepatic triglyceride accumulation in response to a HFD. The decrease in hepatic triglyceride accumulation was mainly due to fewer circulating ceramides, which was in part the result of lower expression of ceramide synthesis genes. The reduction of ceramide levels in the ileum and serum in tempol- or antibiotic-treated mice fed a HFD resulted in downregulation of hepatic SREBP1C and decreased de novo lipogenesis. Administration of C16:0 ceramide to antibiotic-treated mice fed a HFD reversed hepatic steatosis. These studies demonstrate that inhibition of an intestinal FXR/ceramide axis mediates gut microbiota–associated NAFLD development, linking the microbiome, nuclear receptor signaling, and NAFLD. This work suggests that inhibition of intestinal FXR is a potential therapeutic target for NAFLD treatment. PMID:25500885

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

Associations between Longer Habitual Day Napping and Non-Alcoholic Fatty Liver Disease in an Elderly Chinese Population

PubMed Central

Qu, Hua; Wang, Hang; Deng, Min; Wei, Huili; Deng, Huacong

2014-01-01

Context Both longer habitual day napping and Non-Alcoholic Fatty Liver Disease (NAFLD) are associated with diabetes and inflammation, but the association between day napping and NAFLD remains unexplored. Objective To investigate the association between the duration of habitual day napping and NAFLD in an elderly Chinese population and to gain insight into the role of inflammatory cytokines in this association. Design and Setting We conducted a series of cross-sectional studies of the community population in Chongqing, China, from 2011 to 2012. Participants Among 6998 participants aged 40 to 75 years, 6438 eligible participants were included in the first study and analyzed to observe the association between day napping duration and NAFLD. In a separate study, 80 non-nappers and 90 nappers were selected to identify the role of inflammatory cytokines in this association. Logistic regression models were used to examine the odds ratios (ORs) of day nap duration with NAFLD. Results Day nappers had a significantly higher prevalence of NAFLD (P<0.001). Longer day napping duration was associated in a dose-dependent manner with NAFLD (P trend <0.001). After adjustment for potential confounders, the ORs were 1.67 (95% CI 1.13–2.46) for those reporting 0.5–1 h and 1.49 (95% CI 1.01–2.19) for those reporting >1 h of day napping compared with individuals who did not take day naps (all P<0.05). Longer-duration day nappers had higher levels of IL-6 and progranulin (PGRN) but lower levels of Secreted frizzled-related protein-5 (SFRP5, all P trend <0.001). After adjusting for IL-6, PGRN, and SFRP5, the association between day napping duration and NAFLD disappeared (all P>0.05). Conclusion Longer day napping duration is associated with a higher prevalence of NAFLD, and inflammatory cytokines may be an essential link between day napping and NAFLD. PMID:25140521

Higher Estimated Net Endogenous Acid Production May Be Associated with Increased Prevalence of Nonalcoholic Fatty Liver Disease in Chinese Adults in Hong Kong

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

Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto’s method and potential renal acid load (PRAL) was calculated using Remer’s method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to

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

Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Nonalcoholic Fatty Liver Disease.

PubMed

Poulsen, Marianne K; Nellemann, Birgitte; Stødkilde-Jørgensen, Hans; Pedersen, Steen B; Grønbæk, Henning; Nielsen, Søren

2016-04-01

Nonalcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of very low-density lipoprotein-triglyceride (VLDL-TG) kinetics is not fully understood. The objective of the study was to determine VLDL-TG, glucose, and palmitate kinetics during fasting and hyperinsulinemia in men with (NAFLD+) and without NAFLD (NAFLD−). Twenty-seven nondiabetic, upper-body obese (waist to hip ratio > 0.9, body mass index > 28 kg/m2) men, 18 NAFLD+, and nine NAFLD− determined by magnetic resonance spectroscopy were enrolled.14C-labeled VLDL-TG and 3H-labeled glucose and palmitate tracers were applied in combination with indirect calorimetry and breath samples to assess kinetics and substrate oxidations postabsorptively and during a hyperinsulinemic-euglycemic clamp. Dual-X-ray absorptiometry and magnetic resonance imaging assessed body composition. Liver fat content was greater in NAFLD+ than NAFLD− men (21.0% vs 3.7%), even though body composition, metabolites (except triglycerides), and insulin were similar in the groups. Insulin suppression of VLDL-TG secretion (P = .0001), oxidation (P = .0003), and concentration (P= .008) as well as percentage decreases were lower in NAFLD+ than NAFLD− men (secretion: 31.9% ± 17.2% vs 64.7% ± 19.9%; oxidation: −9.0% ± 24.7% vs 46.5% ± 36.6%; concentration: 11.9% ± 20.7% vs 56.2% ± 22.9%, all P < .001). Likewise, lower insulin suppression of very low-density lipoprotein particle size was present in NAFLD+ than NAFLD− men (P = .0002). Conversely, insulin suppression of endogenous glucose production was similar in the groups. Compared with endogenous glucose production, the inability of NAFLD+ men to suppress VLDL-TG kinetics to compensate for the increased liver fat content seems to be an early pathophysiological manifestation of male NAFLD+. These data suggest therapeutic targets reducing liver fat content may ameliorate metabolic abnormalities associated with

Injuries to emergency medicine residents on EMS rotations.

PubMed

Cone, D C; McNamara, R M

1998-01-01

To study the incidence and nature of injuries sustained by emergency medicine (EM) residents during EMS rotations, and steps taken at EM residency programs to increase resident safety during field activities. An eight-question survey form was mailed to all 114 U.S. EM residency directors, with a second mailing to nonresponders eight weeks after the initial mailing. A total of 105 surveys were returned (92%). Six surveys were from new programs whose residents have not yet rotated on EMS. These were excluded from further analysis, leaving 99 programs. Of these, 91 (92%) reported no injuries. One EM resident died in a helicopter crash in 1985. Seven other injury events were reported: 1) facial lacerations, rib fractures, and a shoulder injury in an ambulance accident; 2) an open finger fracture (crushed by a backboard); 3) contusions and a concussion when an ambulance was struck by a fire engine; 4) a groin pull sustained while entering a helicopter; 5) bilateral metatarsal fractures in a fall; 6) rib fractures, a pneumothorax, and a concussion in an ambulance accident; and 7) "minor injuries" sustained in a crash while responding to a scene in a program-owned response vehicle. Actions taken at residency programs to reduce the risk of injury include the use of ballistic vests (four programs), requiring helmets on flights (five programs), and changing flight experience from mandatory to optional (two programs). Ten programs (10%) reported using ground scene safety lectures, and nine programs (15% of those offering flights) reported various types of flight safety instruction. Sixty-nine programs (70%) reported no formal field safety training or other active steps to increase resident safety on EMS rotations. Injuries sustained by EM residents during EMS rotations are uncommon but nontrivial, with several serious injuries and one fatality reported. The majority of EM residency programs have no formal safety training programs for EMS rotations.

Navigating 3D electron microscopy maps with EM-SURFER.

PubMed

Esquivel-Rodríguez, Juan; Xiong, Yi; Han, Xusi; Guang, Shuomeng; Christoffer, Charles; Kihara, Daisuke

2015-05-30

The Electron Microscopy DataBank (EMDB) is growing rapidly, accumulating biological structural data obtained mainly by electron microscopy and tomography, which are emerging techniques for determining large biomolecular complex and subcellular structures. Together with the Protein Data Bank (PDB), EMDB is becoming a fundamental resource of the tertiary structures of biological macromolecules. To take full advantage of this indispensable resource, the ability to search the database by structural similarity is essential. However, unlike high-resolution structures stored in PDB, methods for comparing low-resolution electron microscopy (EM) density maps in EMDB are not well established. We developed a computational method for efficiently searching low-resolution EM maps. The method uses a compact fingerprint representation of EM maps based on the 3D Zernike descriptor, which is derived from a mathematical series expansion for EM maps that are considered as 3D functions. The method is implemented in a web server named EM-SURFER, which allows users to search against the entire EMDB in real-time. EM-SURFER compares the global shapes of EM maps. Examples of search results from different types of query structures are discussed. We developed EM-SURFER, which retrieves structurally relevant matches for query EM maps from EMDB within seconds. The unique capability of EM-SURFER to detect 3D shape similarity of low-resolution EM maps should prove invaluable in structural biology.

Non-alcoholic Fatty Liver Disease: East Versus West

PubMed Central

Agrawal, Swastik; Duseja, Ajay K

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West. PMID:25755421

Effect of enforced physical inactivity induced by 60-day of bed rest on hepatic markers of NAFLD in healthy normal-weight women.

PubMed

Rudwill, Floriane; Bergouignan, Audrey; Gastebois, Caroline; Gauquelin-Koch, Guillemette; Lefai, Etienne; Blanc, Stéphane; Simon, Chantal

2015-06-01

Physical inactivity leads to a cluster of metabolic disorders that have been associated with non-alcoholic fatty liver diseases. We tested whether physical inactivity increases hepatic biomarkers of NAFLDs. Sixteen normal-weight healthy women (body mass index = 21.2 ± 0.5 kg/m(2) ) were studied under controlled energy balance conditions during a previous 60-day bed rest with (n = 8) or without (n = 8) a combined aerobic/resistive exercise protocol. Stored samples were retrospectively used to measure plasma hepatic markers, i.e. steatosis-related alanine and aspartate transaminases, cytokeratin 18 and angiopoietin-like 3, at baseline, after 30 and 60 days of bed rest. Fasting insulin and triglycerides were measured at baseline and after 30 days of bed rest. Two indexes were calculated, one combining alanine and aspartate transaminase and cytokeratin 18 and another cytokeratin 18, homeostasis model assessment of insulin resistance and aspartate aminotransferase. Sixty days of bed rest increased all hepatic markers (P < 0.05 for all) and the two indexes (P < 0.01 for both). Exercise significantly reduced the elevation in aspartate transaminase, cytokeratin 18 and both indexes (P < 0.02 for all) but not the increase in alanine transaminase and angiopoietin-like 3. Changes between baseline and 30 days of bed rest in triglycerides were positively associated with changes in aspartate transaminase (R(2) = 0.28, P = 0.04) suggesting a role of hypertriglyceridaemia in the alteration of liver metabolism under inactive conditions. Physical inactivity increases, independent of fat mass, hepatic markers of steatosis and steatohepatitis. Regular exercise can limit these physical inactivity-induced metabolic alterations. Future studies need to elucidate the underlying mechanisms. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Association of keratin 8/18 variants with non-alcoholic fatty liver disease and insulin resistance in Chinese patients: A case-control study.

PubMed

Li, Rui; Liao, Xian-Hua; Ye, Jun-Zhao; Li, Min-Rui; Wu, Yan-Qin; Hu, Xuan; Zhong, Bi-Hui

2017-06-14

To test the hypothesis that K8/K18 variants predispose humans to non-alcoholic fatty liver disease (NAFLD) progression and its metabolic phenotypes. We selected a total of 373 unrelated adult subjects from our Physical Examination Department, including 200 unrelated NAFLD patients and 173 controls of both genders and different ages. Diagnoses of NAFLD were established according to ultrasonic signs of fatty liver. All subjects were tested for population characteristics, lipid profile, liver tests, as well as glucose tests. Genomic DNA was obtained from peripheral blood with a DNeasy Tissue Kit. K8/K18 coding regions were analyzed, including 15 exons and exon-intron boundaries. Among 200 NAFLD patients, 10 (5%) heterozygous carriers of keratin variants were identified. There were 5 amino-acid-altering heterozygous variants and 6 non-coding heterozygous variants. One novel amino-acid-altering heterozygous variant (K18 N193S) and three novel non-coding variants were observed (K8 IVS5-9A→G, K8 IVS6+19G→A, K18 T195T). A total of 9 patients had a single variant and 1 patient had compound variants (K18 N193S+K8 IVS3-15C→G). Only one R341H variant was found in the control group (1 of 173, 0.58%). The frequency of keratin variants in NAFLD patients was significantly higher than that in the control group (5% vs 0.58%, P = 0.015). Notably, the keratin variants were significantly associated with insulin resistance (IR) in NAFLD patients (8.86% in NAFLD patients with IR vs 2.5% in NAFLD patients without IR, P = 0.043). K8/K18 variants are overrepresented in Chinese NAFLD patients and might accelerate liver fat storage through IR.

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

Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis.

PubMed

Caussy, Cyrielle; Soni, Meera; Cui, Jeffrey; Bettencourt, Ricki; Schork, Nicholas; Chen, Chi-Hua; Ikhwan, Mahdi Al; Bassirian, Shirin; Cepin, Sandra; Gonzalez, Monica P; Mendler, Michel; Kono, Yuko; Vodkin, Irine; Mekeel, Kristin; Haldorson, Jeffrey; Hemming, Alan; Andrews, Barbara; Salotti, Joanie; Richards, Lisa; Brenner, David A; Sirlin, Claude B; Loomba, Rohit

2017-06-30

The risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis. This is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE). The prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438). Using a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients. 140084. National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.

Systematic review with meta-analysis: risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients.

PubMed

Sookoian, S; Pirola, C J

2017-07-01

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is closely associated with the co-occurrence of multiple pathological conditions characterising the metabolic syndrome (MetS), obesity in particular. However, NAFLD also develops in lean subjects, whose risk factors remain poorly defined. We performed a meta-analysis of 15 studies, along with the data pertaining to our own population (n=336 patients). Data from lean (n=1966) and obese (n=5938) patients with NAFLD were analysed; lean (n=9946) and obese (n=6027) subjects without NAFLD served as controls. Relative to the lean non-NAFLD controls, lean patients with NAFLD were older (3.79±0.72 years, P=1.36×10 -6 ) and exhibited the entire spectrum of the MetS risk factors. Specifically, they had a significant (P=10 -10 ) increase in plasma glucose levels (6.44±1.12 mg/dL) and HOMA-IR (0.52±0.094-unit increment), blood lipids (triglycerides: 48.37±3.6, P=10 -10 and total cholesterol: 7.04±3.8, mg/dL, P=4.2×10 -7 ), systolic (5.64±0.7) and diastolic (3.37±0.9) blood pressure (mm Hg), P=10 -10 , and waist circumference (5.88±0.4 cm, P=10 -10 ); values denote difference in means±SE. Nevertheless, the overall alterations in the obese group were much more severe when compared to lean subjects, regardless of the presence of NAFLD. Meta-regression suggested that NAFLD is a modifier of the level of blood lipids. Lean and obese patients with NAFLD share a common altered metabolic and cardiovascular profile. The former, while having normal body weight, showed excess of abdominal adipose tissue as well as other MetS features. © 2017 John Wiley & Sons Ltd.

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.

Prevalence of Hypothyroidism in Nonalcoholic Fatty Liver disease

PubMed Central

Pagadala, Mangesh R.; Zein, Claudia O.; Dasarathy, Srinivasan; Yerian, Lisa; Lopez, Rocio; McCullough, Arthur J.

2014-01-01

Background A possible association between nonalcoholic fatty liver disease (NAFLD) and hypothyroidism has been suggested. Possible explanations for this association are the recognized links between hypothyroidism and various elements of the metabolic syndrome which is often present in NAFLD. To further explore this association, we determined the prevalence of hypothyroidism in a cohort of patients with NAFLD and analyzed the potential factors associated with hypothyroidism in this patient population. Methods Two hundred and forty six patients with biopsy proven NAFLD attending hepatology clinics at the Cleveland Clinic between October 2006 to June 2009 and 430 age, gender, race and BMI matched control subjects seen in the general internal medicine clinic were included. Patients with a clinical diagnosis of hypothyroidism who were on thyroid replacement therapy were considered to be hypothyroid. Results Hypothyroidism was more frequent among patients with NAFLD (21%vs 9.5%.; P<0.01) compared to controls and was higher in NASH patients than NAFLD patients without NASH (25% vs 12.8%, P=0.03). Subjects with hypothyroidism were 2.1 (95% CI: 1.1, 3.9,P=0.02)) and 3.8 (95% CI:2,6.9, P<0.001) times more likely to have NAFLD and NASH respectively. By Multivariate analysis, female gender (P<0.001) and increased BMI (P=.03) were associated with hypothyroidism. NAFLD subjects who reported mild alcohol consumption were less likely to have hypothyroidism compared to those who reported complete abstinence (OR 0.37, P=0.008). Conclusions A higher prevalence of hypothyroidism was demonstrated in patients with NAFLD compared to controls. Patients with hypothyroidism were more likely to have NASH. Among subjects with NALFD, female gender, increased BMI and history of abstinence from alcohol were associated with hypothyroidism. Further studies are needed in order to confirm and better characterized these findings as well as the described associations and their pathogenesis. PMID

The triglyceride and glucose index (TyG) is an effective biomarker to identify nonalcoholic fatty liver disease.

PubMed

Zhang, Shujun; Du, Tingting; Zhang, Jianhua; Lu, Huiming; Lin, Xuan; Xie, Junhui; Yang, Yan; Yu, Xuefeng

2017-01-19

The triglyceride and glucose index (TyG) has been proposed as a marker of insulin resistance. We aimed to investigate the ability of TyG, through comparing with the predictive value of alanine aminotransferase (ALT), to identify individuals at risk for nonalcoholic fatty liver disease (NAFLD). A cross-sectional study was conducted in a Chinese health examination cohort of 10 761 people aged above 20 years. NAFLD was diagnosed by ultrasonography. Compared with the participants in the lowest quartile of TyG, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were 1.8 (1.5-2.1), 3.0 (2.5-3.5), and 6.3 (5.3-7.5) for those in the second, the third, and the fourth quartile of TyG, whereas the corresponding ORs (95% CI) for NAFLD were 1.5 (1.3-1.7), 1.9 (1.6-2.2), and 3.1 (2.6-3.7) for the upper three quartiles of ALT. These results suggested that TyG was superior to ALT in association with NAFLD risk. According to the ROC analysis, the optimal cut-off point of TyG for NAFLD was 8.5 and the area under the ROC curve (AUC) was 0.782 (95% CI 0.773-0.790), with 72.2 and 70.5% sensitivity and specificity, respectively. The AUC of TyG was larger than that of ALT (0.715 (95% CI 0.705-0.725), P for difference <0.0001), whereas the largest AUC was obtained when adding TyG to ALT (0.804 (95% CI 0.795-0.812), P for difference <0.0001). TyG is effective to identify individuals at risk for NAFLD. A TyG threshold of 8.5 was highly sensitive for detecting NAFLD subjects and may be suitable as a diagnostic criterion for NAFLD in Chinese adults.

Deoxyribonucleic acid telomere length shortening can predict the incidence of non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus.

PubMed

Ping, Fan; Li, Zeng-Yi; Lv, Ke; Zhou, Mei-Cen; Dong, Ya-Xiu; Sun, Qi; Li, Yu-Xiu

2017-03-01

To investigate the effect of telomere shortening and other predictive factors of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus patients in a 6-year prospective cohort study. A total of 70 type 2 diabetes mellitus (mean age 57.8 ± 6.7 years) patients without NAFLD were included in the study, and 64 of them were successfully followed up 6 years later, excluding four cases with significant alcohol consumption. NAFLD was diagnosed by the hepatorenal ratio obtained by a quantitative ultrasound method using NIH image analysis software. The 39 individuals that developed NAFLD were allocated to group A, and the 21 individuals that did not develop NAFLD were allocated to group B. Fluorescent real-time quantitative polymerase chain reaction was used to measure telomere length. There was no significant difference between the two groups in baseline telomere length; however, at the end of the 6th year, telomere length had become shorter in group A compared with group B. There were significant differences between these two groups in baseline body mass index, waistline, systolic blood pressure, glycated hemoglobin and fasting C-peptide level. In addition, the estimated indices of baseline insulin resistance increased in group A. Fasting insulin level, body mass index, systolic blood pressure at baseline and the shortening of telomere length were independent risk factors of NAFLD in type 2 diabetes mellitus patients. Telomere length became shorter in type 2 diabetes mellitus patients who developed NAFLD over the course of 6 years. Type 2 diabetes mellitus patients who developed NAFLD had more serious insulin resistance compared with those who did not develop NAFLD a long time ago. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Diabetes mellitus and non-alcoholic fatty liver disease: the thread of Ariadne.

PubMed

Kosmidou, Maria; Milionis, Haralampos

2017-06-01

Non alcoholic fatty liver disease (NAFLD, the hepatic fat accumulation) and non alcoholic steatohepatitis (NASH, the aggressive form of liver steatosis plus inflammation and hepatocyte necrosis) are reaching epidemic dimensions in subjects with diabetes mellitus (DM). Taking into account that the incidence of DM increases worldwide, these entities represent major health problems. There is accumulating evidence that diabetic subjects with NASH are at increased risk not only for cardiovascular disease compications but also for cirrhosis and hepatocellular cancer. On the other hand, the presence of NAFLD correlates with an increased risk for the development of DM. The most-widely accepted pathophysiological mechanisms relating DM and NAFLD include central obesity and insulin resistanc, but new insights are under scrutiny. Therapeutic modalities used for the management of diabetes have been studied for their impact on NAFLD/NASH and both neutral and beneficial effects have been reported. In this review, we discuss issues regarding the epidemiology, the pathophysiological pathways relating NAFLD with DM and consider strategies that may be useful in the management of NAFLD in the diabetic population.

Novel circulating biomarkers for non-alcoholic fatty liver disease: A systematic review.

PubMed

Sahebkar, Amirhossein; Sancho, Elena; Abelló, David; Camps, Jordi; Joven, Jorge

2018-02-01

Currently, a liver biopsy remains the only reliable way to precisely diagnose non-alcoholic fatty liver disease (NAFLD) and establish the severity of liver injury, presence of fibrosis, and architecture remodeling. However, the cost and the intrinsic invasive procedure of a liver biopsy rules it out as a gold standard diagnostic test, and the imaging test are not the best choice due to the price, and currently is being refined. The lack of a biomarker of NAFLD pushes to develop this new line of research. The aim of the present systematic review is to clarify and update all the NAFLD biomarkers described in the literature until recently. We highlight α-ketoglutarate and CK18-F as currently the best potential biomarker of NAFLD. However, due to methodological differences, we propose the implementation of international, multicenter, multiethnic studies with larger population size, and biopsy proven NAFLD diagnosis to analyze and compare α-ketoglutarate and CK18-F as potential biomarkers of the silent evolution of NAFLD. © 2017 Wiley Periodicals, Inc.

Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

PubMed Central

Aigner, Elmar; Weiss, Günter; Datz, Christian

2015-01-01

Elevated iron stores as indicated by hyperferritinemia with normal or mildly elevated transferrin saturation and mostly mild hepatic iron deposition are a characteristic finding in subjects with non-alcoholic fatty liver disease (NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the “dysmetabolic iron overload syndrome”. Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxyl-radicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications. PMID:25729473

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.

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.

Pulmonary function in children and adolescents with sickle cell disease: have we paid proper attention to this problem?

PubMed

Vieira, Ana Karine; Alvim, Cristina Gonçalves; Carneiro, Maria Cristina Marquez; Ibiapina, Cássio da Cunha

2016-01-01

To evaluate pulmonary function and functional capacity in children and adolescents with sickle cell disease. This was a cross-sectional study involving 70 children and adolescents (8-15 years of age) with sickle cell disease who underwent pulmonary function tests (spirometry) and functional capacity testing (six-minute walk test). The results of the pulmonary function tests were compared with variables related to the severity of sickle cell disease and history of asthma and of acute chest syndrome. Of the 64 patients who underwent spirometry, 15 (23.4%) showed abnormal results: restrictive lung disease, in 8 (12.5%); and obstructive lung disease, in 7 (10.9%). Of the 69 patients who underwent the six-minute walk test, 18 (26.1%) showed abnormal results regarding the six-minute walk distance as a percentage of the predicted value for age, and there was a ≥ 3% decrease in SpO2 in 36 patients (52.2%). Abnormal pulmonary function was not significantly associated with any of the other variables studied, except for hypoxemia and restrictive lung disease. In this sample of children and adolescents with sickle cell disease, there was a significant prevalence of abnormal pulmonary function. The high prevalence of respiratory disorders suggests the need for a closer look at the lung function of this population, in childhood and thereafter. Avaliar a função pulmonar e a capacidade funcional em crianças e adolescentes com doença falciforme. Estudo transversal com 70 crianças e adolescentes com doença falciforme (8-15 anos), submetidos a testes de função respiratória (espirometria) e de capacidade funcional (teste de caminhada de seis minutos). Os resultados da avaliação da função pulmonar foram comparados com variáveis relacionadas à gravidade da doença falciforme e à presença de história de asma e de síndrome torácica aguda. Dos 64 pacientes submetidos à espirometria, 15 (23,4%) apresentaram resultados alterados: distúrbio ventilatório restritivo, em

Where There is No EMS: Lay Providers in Emergency Medical Services Care - EMS as a Public Health Priority.

PubMed

Debenham, Sierra; Fuller, Matthew; Stewart, Matthew; Price, Raymond R

2017-12-01

By 2030, road traffic accidents are projected to be the fifth leading cause of death worldwide, with 90% of these deaths occurring in low- and middle-income countries (LMICs). While high-quality, prehospital trauma care is crucial to reduce the number of trauma-related deaths, effective Emergency Medical Systems (EMS) are limited or absent in many LMICs. Although lay providers have long been recognized as the front lines of informal trauma care in countries without formal EMS, few efforts have been made to capitalize on these networks. We suggest that lay providers can become a strong foundation for nascent EMS through a four-fold approach: strengthening and expanding existing lay provider training programs; incentivizing lay providers; strengthening locally available first aid supply chains; and using technology to link lay provider networks. Debenham S , Fuller M , Stewart M , Price RR . Where there is no EMS: lay providers in Emergency Medical Services care - EMS as a public health priority. Prehosp Disaster Med. 2017;32(6):593-595.

Overweight effect on spirometric parameters in adolescents undergoing exercise.

PubMed

Costa, Rayana de Oliveira; Silva, Juliana Pereira; Lacerda, Eliana Mattos; Dias, Rodrigo; Pezolato, Vitor Alexandre; Silva, Carlos Alberto da; Krinski, Kleverton; Correia, Marco Aurélio de Valois; Cieslak, Fabrício

2016-01-01

To evaluate effects of overweight on spirometric parameters in adolescents who underwent bronchial provocation test for exercise. We included 71 male adolescents. The diagnosis of asthma was done based on participants' clinical history and on the International Study Questionnaire Asthma and Allergies in Childhood, and the diagnosis of obesity was based on body mass index above 95th percentile. The bronchospasm induced by exercise was assessed using the run-walk test on a treadmill for eight minutes. The decrease in forced expiratory volume in one second > or equal to 10% before exercise was considered positive, and to calculate the intensity in exercise-induced bronchospasm we measured the maximum percentage of forced expiratory volume in one second and above the curve area. Data analysis was carried out using the Mann-Whitney U test and Friedman test (ANOVA), followed by Wilcoxon test (p<0.05). In addition, we used Fisher's exact test to analyze the exercise-induced bronchospasm frequency. Significant differences were observed among obese adolescents in exercise-induced bronchospasm frequency (p=0,013) and in relation to time required for recovery after exercise (p=0,007). Overweight can influence the increase in the exercise-induced bronchospasm frequency in non-asthmatic adolescents compared with eutrophic adolescents. Avaliar o efeito do excesso de peso sobre parâmetros espirométricos em adolescentes submetidos ao teste de broncoprovocação por exercício. Participaram do estudo 71 adolescentes do sexo masculino. O diagnóstico de asma foi obtido por meio de histórico clínico e do questionário International Study of Asthma and Allergies in Childhood, e o de obesidade, pelo índice de massa corporal acima do percentil 95. Para avaliar o broncoespasmo induzido pelo exercício, utilizou-se o teste correr/caminhar em esteira ergométrica, com duração de 8 minutos, considerando positivo se diminuição do volume expiratório forçado no primeiro segundo >10

Association between non-alcoholic fatty liver disease and peripheral artery disease in patients with type 2 diabetes.

PubMed

Zou, Yaowu; Li, Xinde; Wang, Can; Wang, Jing; Wang, Fei; Ma, Lidan; You, Wenjun; Li, Changgui

2017-10-01

Non-alcoholic fatty liver disease (NAFLD) is associated with the risk of coronary heart diseases; however, the relationship between NAFLD and peripheral artery disease (PAD) in patients with type 2 diabetes has not been investigated. To investigate the association between NAFLD and PAD in patients with type 2 diabetes. We carried out a cross-sectional study on 2646 type 2 diabetes patients ≥ 40 years. All patients provided fasting blood samples and underwent a liver ultrasonography and ankle-brachial index (ABI) test. PAD was defined as an ABI <0.9. Multiple logistic regression analyses were performed to investigate the odds ratio (OR) for PAD associated with NAFLD. Our analyses showed that patients with NAFLD had a significantly higher prevalence of PAD compared with those without NAFLD (12.8% vs 7.8%). NAFLD was associated with a 75% (OR 1.75, 95% confidence interval (CI) 1.35-2.28) increased risk of PAD after adjustment for demographic factors. Addition of various metabolic risk factors as confounders attenuated the association (OR 1.49, 95% CI 1.12-2.00). Further adjustment for C-reactive protein led the association to be marginally significant (OR 1.33, 95% CI 0.99-1.80). Analyses stratified by gender suggested the association was much stronger among women than among men. Type 2 diabetes patients with NAFLD had a higher prevalence of PAD, and this association was partly, but not entirely, explained by metabolic risk factors and inflammation. © 2017 Royal Australasian College of Physicians.

Animal models of non-alcoholic fatty liver disease: current perspectives and recent advances.

PubMed

Lau, Jennie Ka Ching; Zhang, Xiang; Yu, Jun

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. NAFLD progresses from simple liver steatosis to non-alcoholic steatohepatitis and, in more severe cases, to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Because of its growing worldwide prevalence, various animal models that mirror both the histopathology and the pathophysiology of each stage of human NAFLD have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field. This review presents a critical analysis of the histopathology and pathogenesis of NAFLD, the most frequently used and recently developed animal models for each stage of NAFLD and NAFLD-induced HCC, the main mechanisms involved in the experimental pathogenesis of NAFLD in different animal models, and a brief summary of recent therapeutic targets found by the use of animal models. Integrating the data from human disease with those from animal studies indicates that, although current animal models provide critical guidance in understanding specific stages of NAFLD pathogenesis and progression, further research is necessary to develop more accurate models that better mimic the disease spectrum, in order to provide both increased mechanistic understanding and identification/testing of novel therapeutic approaches. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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

Low serum potassium level is associated with nonalcoholic fatty liver disease and its related metabolic disorders.

PubMed

Sun, Kan; Lu, Jieli; Jiang, Yiran; Xu, Min; Xu, Yu; Zhang, Jie; Xu, Baihui; Sun, Jichao; Sun, Wanwan; Ren, Chenxi; Liu, Jianmin; Wang, Weiqing; Bi, Yufang; Ning, Guang

2014-03-01

Subjects with nonalcoholic fatty liver disease (NAFLD) have a high risk of developing type 2 diabetes and cardiovascular diseases. Low serum potassium concentration or low dietary potassium intake can result in metabolic disorders. Our objective was to evaluate the association between low serum potassium level and prevalence of NAFLD in a Chinese population. A population-based cross-sectional study. We conducted a community-based study in 8592 subjects to investigate the association of serum potassium with the risk of prevalent NAFLD. NAFLD was diagnosed by hepatic ultrasonography. The prevalence rate of NAFLD was 30·3% in this population and gradually decreased across serum potassium quartiles. With the reduction in serum potassium level, participants have larger waist circumference (WC) and more severe insulin resistance. The correlations hold also in multivariate linear regression analysis. In logistic regression analysis, compared with subjects in the highest quartile of serum potassium level, the adjusted odds ratios (ORs) in the lowest quartile was 1·33 [95% confidence interval (CI), 1·11-1·60] for NAFLD, 1·81 (95% CI, 1·49-2·19) for insulin resistance and 1·58 (95% CI, 1·30-1·93) for central obesity. In subgroup analysis after multiple adjustments, significant relation between serum potassium level and prevalent NAFLD was detected in women, younger subjects, those with insulin resistance and those with central obesity, respectively. Low serum potassium level significantly associated with prevalence of NAFLD in middle-aged and elderly Chinese. © 2013 John Wiley & Sons Ltd.

Self-reported eating speed in relation to non-alcoholic fatty liver disease in adults.

PubMed

Lee, Saehyun; Ko, Byung-Joon; Gong, Younghoon; Han, Kyungdo; Lee, Anna; Han, Byoung-Duck; Yoon, Yeo Joon; Park, Siyoung; Kim, Jung-Hyun; Mantzoros, Christos S

2016-02-01

Non-alcoholic fatty liver disease (NAFLD), known to be related to insulin resistance, has been the focus of intensive research efforts due to its increasing prevalence and clinical significance. Rapid eating behavior is another emerging health issue associated with insulin resistance. We aimed to clarify the correlation between self-reported eating speed and NAFLD, both known to be related to insulin resistance. A cross-sectional study was conducted during routine medical checkups on 7,917 consecutively enrolled participants. Anthropometric, biochemical, nutritional, and social parameters were checked. The self-reported eating speed per their usual meal (<5, 5-10, 10-15, and more than 15 min) was recorded by a registered dietitian. The faster eating groups had a higher proportion of NAFLD, and the grade of NAFLD was advanced. After controlling for anthropometric, cardiometabolic, social, and nutritional parameters, the fastest eating group (<5 min) showed an increased risk of NAFLD compared with the lowest eating speed group (≥15 min) both in total [odds ratio (OR) 1.81, 95% confidence interval (CI) 1.24-2.63] and the participants with BMI < 25 kg/m(2) (OR 1.79, 95% CI 1.22-2.61). As the self-reported eating speed increased, the risk of NAFLD also increased in total and those with BMI < 25 kg/m(2) (P for trend <0.001). Fast eating is associated with an increased risk of the presence and grade of NAFLD in Korean adults, especially those with BMI < 25 kg/m(2), since presence of overweight or obesity may be overwhelming the effect on NAFLD.

Analysis of breath volatile organic compounds as a noninvasive tool to diagnose nonalcoholic fatty liver disease in children.

PubMed

Alkhouri, Naim; Cikach, Frank; Eng, Katharine; Moses, Jonathan; Patel, Nishaben; Yan, Chen; Hanouneh, Ibrahim; Grove, David; Lopez, Rocio; Dweik, Raed

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is one of the most common complications of childhood obesity. Our objective was to investigate the association of breath volatile organic compounds with the diagnosis of NAFLD in children. Patients were screened with an ultrasound of the abdomen to evaluate for NAFLD. Exhaled breath was collected and analyzed per protocol using selective ion flow tube mass spectrometry (SIFT-MS). Sixty patients were included in the study (37 with NAFLD and 23 with normal liver). All children were overweight or obese. The mean age was 14.1±2.8 years and 50% were female. A comparison of the SIFT-MS results of patients with NAFLD with those with normal liver on ultrasound revealed differences in concentration of more than 15 compounds. A panel of four volatile organic compounds can identify the presence of NAFLD with good accuracy (area under the receiver operating characteristic curve of 0.913 in the training set and 0.763 in the validation set). Breath isoprene, acetone, trimethylamine, acetaldehyde, and pentane were significantly higher in the NAFLD group compared with normal liver group (14.7 ppb vs. 8.9 for isoprene; 71.7 vs. 36.9 for acetone; 5.0 vs. 3.2 for trimethylamine; 35.1 vs. 26.0 for acetaldehyde; and 13.3 vs. 8.8 for pentane, P<0.05 for all). Exhaled breath analysis is a promising noninvasive method to detect fatty liver in children. Isoprene, acetone, trimethylamine, acetaldehyde, and pentane are novel biomarkers that may help to gain insight into pathophysiological processes leading to the development of NAFLD.

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

Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease

PubMed Central

Hashemi, Mohammad; Hanafi Bojd, Hamideh; Eskandari Nasab, Ebrahim; Bahari, Ali; Hashemzehi, Noor Allah; Shafieipour, Sara; Narouie, Behzad; Taheri, Mohsen; Ghavami, Saeid

2013-01-01

Background Genetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). Adiponectin is a white and brown adipose tissue hormone, and have been found to play essential roles in the regulation of energy homoeostasis. Recent reports have identified a possible role of adiponectin in NAFLD via PPARγ pathway. Objectives The present study was designed to find out the impact of adiponectin rs1501299 (276G/T) and rs266729 (-11377C/G) gene polymorphisms in NAFLD. Patients and Methods Eighty-three patients with diagnosis of NAFLD, and 93 healthy subjects were included in the study. Tetra ARMS-PCR was designed to detect single nucleotide polymorphisms. Results A significant difference was found between NAFLD and control group regarding the rs266729 polymorphism (χ2 = 7.35, P = 0.025). The rs266729 polymorphism increased the risk of NAFLD in codominant (CC vs. CG: OR = 2.18, 95% CI = 1.16 - 4.12, P = 0.016) and dominant (CC vs. CG/GG: OR = 2.31, 95% CI = 1.25 - 4.27; P = 0.008) inheritance tested models. The G allele increased the risk of NAFLD (OR = 1.63, 95% CI = 1.03 - 2.57, P = 0.037) in comparison with C allele. No significant difference was found between the groups concerning adiponectin rs1501299 gene polymorphism (χ2 = 0.70, P = 0.697). Conclusions adiponectin rs266729 polymorphism might be a candidate gene, which determines the susceptibility to NAFLD. Larger studies are necessary to confirm these findings in various populations. PMID:23922565

Infant nutrition and maternal obesity influence the risk of non-alcoholic fatty liver disease in adolescents.

PubMed

Ayonrinde, Oyekoya T; Oddy, Wendy H; Adams, Leon A; Mori, Trevor A; Beilin, Lawrence J; de Klerk, Nicholas; Olynyk, John K

2017-09-01

The pathway to non-alcoholic fatty liver disease (NAFLD) in adolescents may have its origins in adiposity gains, nutrition and sedentary lifestyle established during childhood. There is inadequate knowledge regarding the associations between infant nutrition and subsequent NAFLD. We examined the association of maternal factors and infant nutrition, with the subsequent diagnosis of NAFLD in adolescents. Adolescents aged 17years in the Western Australian Pregnancy (Raine) Cohort study had fatty liver assessment using liver ultrasound. Prospectively recorded data on maternal pregnancy and infant feeding were examined against a NAFLD outcome during late adolescence. NAFLD was diagnosed in 15.2% of the 1,170 adolescents examined. Ninety-four percent had been breastfed as infants. The duration of breastfeeding before starting supplementary milk was ⩾4months in 54.4% and ⩾6months in 40.6%. Breastfeeding without supplementary milk ⩾6months (adjusted odds ratio [OR]: 0.64; 95% confidence interval [CI]: 0.43-0.94, p=0.02), maternal pre-pregnancy obesity (adjusted OR: 2.29; 95% CI: 1.21-4.32, p=0.01) and adolescent obesity (adjusted OR: 9.08; 95% CI: 6.26-13.17, p<0.001) were associated with NAFLD independent of a Western dietary pattern at 17years of age. Adolescents with NAFLD who had been breastfed for ⩾6months had a less adverse metabolic profile compared with adolescents breastfed for <6months. Supplementary milk intake starting before 6months was associated with a higher prevalence and ultrasound severity of NAFLD compared with intake starting after 6months (17.7% vs. 11.2%, p=0.003 and 7.8% vs. 3.4%, p=0.005 respectively). Though NAFLD is generally mediated through adiposity gains, breastfeeding for at least 6months, avoidance of early supplementary formula milk feeding, and normal maternal pre-pregnancy BMI may reduce the odds of a NAFLD diagnosis during adolescence. Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder in which there is too

An Analysis of EMS and ED Detection of Stroke.

PubMed

Medoro, Ian; Cone, David C

2017-01-01

Studies have shown a reduction in time-to-CT and improved process measures when EMS personnel notify the ED of a "stroke alert" from the field. However, there are few data on the accuracy of these EMS stroke alerts. The goal of this study was to examine diagnostic test performance of EMS and ED stroke alerts and related process measures. The EMS and ED records of all stroke alerts in a large tertiary ED from August 2013-January 2014 were examined and data abstracted by one trained investigator, with data accuracy confirmed by a second investigator for 15% of cases. Stroke alerts called by EMS prior to ED arrival were compared to stroke alerts called by ED physicians and nurses (for walk-in patients, and patients transported by EMS without EMS stroke alerts). Means ± SD, medians, unpaired t-tests (for continuous data), and two-tailed Fisher's exact tests (for categorical data) were used. Of 260 consecutive stroke alerts, 129 were EMS stroke alerts, and 131 were ED stroke alerts (70 called by physicians, 61 by nurses). The mean NIH Stroke Scale was higher in the EMS group (8.1 ± 7.6 vs. 3.0 ± 5.0, p < 0.0001). The positive predictive value of EMS stroke alerts was 0.60 (78/129), alerts by ED nurses was 0.25 (15/61), and alerts by ED physicians was 0.31 (22/70). The PPV for EMS was better than for nurses or physicians (both p < 0.001), and more patients in the EMS group had final diagnoses of stroke (62/129 vs. 24/131, p < 0.001). The positive likelihood ratio was 1.53 for EMS personnel, 0.45 for physicians, and 0.77 for nurses. The mean time to order the CT (8.5 ± 7.1 min vs. 23.1 ± 18.2 min, p < 0.0001) and the mean ED length of stay (248 ± 116 min vs. 283 ± 128 min, p = 0.022) were shorter for the EMS stroke alert group. More EMS stroke alert patients received tPA (16/129 vs. 6/131, p = 0.027). EMS stroke alerts have better diagnostic test performance than stroke alerts by ED staff, likely due to higher NIH Stroke Scale scores (more obvious

An economic toolkit for identifying the cost of emergency medical services (EMS) systems: detailed methodology of the EMS Cost Analysis Project (EMSCAP).

PubMed

Lerner, E Brooke; Garrison, Herbert G; Nichol, Graham; Maio, Ronald F; Lookman, Hunaid A; Sheahan, William D; Franz, Timothy R; Austad, James D; Ginster, Aaron M; Spaite, Daniel W

2012-02-01

Calculating the cost of an emergency medical services (EMS) system using a standardized method is important for determining the value of EMS. This article describes the development of a methodology for calculating the cost of an EMS system to its community. This includes a tool for calculating the cost of EMS (the "cost workbook") and detailed directions for determining cost (the "cost guide"). The 12-step process that was developed is consistent with current theories of health economics, applicable to prehospital care, flexible enough to be used in varying sizes and types of EMS systems, and comprehensive enough to provide meaningful conclusions. It was developed by an expert panel (the EMS Cost Analysis Project [EMSCAP] investigator team) in an iterative process that included pilot testing the process in three diverse communities. The iterative process allowed ongoing modification of the toolkit during the development phase, based upon direct, practical, ongoing interaction with the EMS systems that were using the toolkit. The resulting methodology estimates EMS system costs within a user-defined community, allowing either the number of patients treated or the estimated number of lives saved by EMS to be assessed in light of the cost of those efforts. Much controversy exists about the cost of EMS and whether the resources spent for this purpose are justified. However, the existence of a validated toolkit that provides a standardized process will allow meaningful assessments and comparisons to be made and will supply objective information to inform EMS and community officials who are tasked with determining the utilization of scarce societal resources. © 2012 by the Society for Academic Emergency Medicine.

Nonalcoholic fatty liver disease: A comprehensive review of a growing epidemic

PubMed Central

Hassan, Kareem; Bhalla, Varun; Ezz El Regal, Mohammed; A-Kader, H Hesham

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD. PMID:25232245

Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology.

PubMed

Gao, Xin; Fan, Jian-Gao

2013-12-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, affecting 20%-33% of the general population. Large population-based surveys in China indicate a prevalence of approximately 15%-30%. Worldwide, including in China, the prevalence of NAFLD has increased rapidly in parallel with regional trends of obesity, type 2 diabetes and metabolic syndrome. In addition, NAFLD has contributed significantly to increased overall, as well as cardiovascular and liver-related, mortality in the general population. In view of rapid advances in research into NAFLD in recent years, this consensus statement provides a brief update on the progress in the field and suggests preferred approaches for the comprehensive management of NAFLD and its related metabolic diseases. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

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.

Epigenetic mechanisms in non-alcoholic fatty liver disease: An emerging field.

PubMed

Gallego-Durán, Rocío; Romero-Gómez, Manuel

2015-10-28

Non-alcoholic fatty liver disease (NAFLD) is an emerging health concern in both developed and non-developed world, encompassing from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Incidence and prevalence of this disease are increasing due to the socioeconomic transition and change to harmful diet. Currently, gold standard method in NAFLD diagnosis is liver biopsy, despite complications and lack of accuracy due to sampling error. Further, pathogenesis of NAFLD is not fully understood, but is well-known that obesity, diabetes and metabolic derangements played a major role in disease development and progression. Besides, gut microbioma and host genetic and epigenetic background could explain considerable interindividual variability. Knowledge that epigenetics, heritable events not caused by changes in DNA sequence, contribute to development of diseases has been a revolution in the last few years. Recently, evidences are accumulating revealing the important role of epigenetics in NAFLD pathogenesis and in NASH genesis. Histone modifications, changes in DNA methylation and aberrant profiles or microRNAs could boost development of NAFLD and transition into clinical relevant status. PNPLA3 genotype GG has been associated with a more progressive disease and epigenetics could modulate this effect. The impact of epigenetic on NAFLD progression could deserve further applications on therapeutic targets together with future non-invasive methods useful for the diagnosis and staging of NAFLD.

Traditional Chinese herbal extracts inducing autophagy as a novel approach in therapy of nonalcoholic fatty liver disease

PubMed Central

Liu, Cong; Liao, Jia-Zhi; Li, Pei-Yuan

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases around the world due to the modern sedentary and food-abundant lifestyle, which is characterized by excessive fat accumulation in the liver related with causes other than alcohol abuse. It is widely acknowledged that insulin resistance, dysfunctional lipid metabolism, endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis/necrosis may all contribute to NAFLD. Autophagy is a protective self-digestion of intracellular organelles, including lipid droplets (lipophagy), in response to stress to maintain homeostasis. Lipophagy is another pathway for lipid degradation besides lipolysis. It is reported that impaired autophagy also contributes to NAFLD. Some studies have suggested that the histological characteristics of NAFLD (steatosis, lobular inflammation, and peri-sinusoid fibrosis) might be improved by treatment with traditional Chinese herbal extracts, while autophagy may be induced. This review will provide insights into the characteristics of autophagy in NAFLD and the related role/mechanisms of autophagy induced by traditional Chinese herbal extracts such as resveratrol, Lycium barbarum polysaccharides, dioscin, bergamot polyphenol fraction, capsaicin, and garlic-derived S-allylmercaptocysteine, which may inhibit the progression of NAFLD. Regulation of autophagy/lipophagy with traditional Chinese herbal extracts may be a novel approach for treating NAFLD, and the molecular mechanisms should be elucidated further in the near future. PMID:28373762

Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

PubMed Central

Lim, Jun Wei; Dillon, John; Miller, Michael

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patient-disease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) anti-inflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production. PMID:25024592

Epidemiology and Natural History of Non-alcoholic Fatty Liver Disease

PubMed Central

Mishra, Alita; Younossi, Zobair M

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease burden across the world. By definition, although the histopathologic features of NAFLD are identical to that of alcoholic liver disease, its diagnosis requires absence of significant alcohol use and absence of other causes of chronic liver disease. We now know that NAFLD is not simply a disease of the Western world. It is manifested across the world, in varying rates, across gender, across varying ethnicities, and in its association with other host factors. In this review article, the definition of NAFLD, its spectrum, ranging from mild steatosis to hepatocellular injury and inflammation defined as non-alcoholic steatohepatitis (NASH) is discussed. Mild steatosis is generally a stable disease whereas NASH can be progressive. Based on current published literature, current incidence and prevalence of NAFLD and NASH are discussed. It is also accepted that these processes will continue to increase in prevalence with the rise of obesity, type II diabetes, and associated metabolic syndrome. Some of the risk factors have been well-established and are discussed. In addition, this review also presents emerging associations with other risk factors for NAFLD. Natural history of NAFLD is variable depending upon the histologic subtypes and other underlying comorbidities and is discussed in this review as well. PMID:25755422

The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background

PubMed Central

Marsh, Sharon; Hu, Junbo; Feng, Wenke

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) in PNPLA3 and rs58542926 (Glu167Lys) in TM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression. PMID:27247565

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

Nonalcoholic fatty liver disease is associated with aortic valve sclerosis in patients with type 2 diabetes mellitus.

PubMed

Bonapace, Stefano; Valbusa, Filippo; Bertolini, Lorenzo; Pichiri, Isabella; Mantovani, Alessandro; Rossi, Andrea; Zenari, Luciano; Barbieri, Enrico; Targher, Giovanni

2014-01-01

Recent epidemiological data suggest that non-alcoholic fatty liver disease (NAFLD) is closely associated with aortic valve sclerosis (AVS), an emerging risk factor for adverse cardiovascular outcomes, in nondiabetic and type 2 diabetic individuals. To date, nobody has investigated the association between NAFLD and AVS in people with type 2 diabetes, a group of individuals in which the prevalence of these two diseases is high. We recruited 180 consecutive type 2 diabetic patients without ischemic heart disease, valvular heart disease, hepatic diseases or excessive alcohol consumption. NAFLD was diagnosed by liver ultrasonography whereas AVS was determined by conventional echocardiography in all participants. In the whole sample, 120 (66.7%) patients had NAFLD and 53 (29.4%) had AVS. No patients had aortic stenosis. NAFLD was strongly associated with an increased risk of prevalent AVS (odds ratio [OR] 2.79, 95% CI 1.3-6.1, p<0.01). Adjustments for age, sex, duration of diabetes, diabetes treatment, body mass index, smoking, alcohol consumption, hypertension, dyslipidemia, hemoglobin A1c and estimated glomerular filtration rate did not attenuate the strong association between NAFLD and risk of prevalent AVS (adjusted-OR 3.04, 95% CI 1.3-7.3, p = 0.01). Our results provide the first demonstration of a positive and independent association between NAFLD and AVS in patients with type 2 diabetes mellitus.

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.

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

Nonalcoholic Fatty Liver Disease Is Associated with Increased Risk of Reflux Esophagitis.

PubMed

Yang, Hyo-Joon; Chang, Yoosoo; Park, Soo-Kyung; Jung, Yoon Suk; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Ryu, Seungho; Sohn, Chong Il

2017-12-01

Reflux esophagitis is associated with obesity and metabolic syndrome; however, the relationship between nonalcoholic fatty liver disease (NAFLD) and reflux esophagitis is unclear. We examined the association between NAFLD and the development of reflux esophagitis. Our cohort consisted of 117,377 Korean adults without reflux esophagitis at baseline who underwent a health checkup program including upper endoscopy between 2002 and 2014 and were followed annually or biennially until December 2014. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or any other identifiable cause. Over 520,843.2 person-years of follow-up, 22,500 participants developed reflux esophagitis (incidence density, 43.2 per 1000 person-years). In models adjusted for age and sex, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) for incident reflux esophagitis in subjects with NAFLD compared to those without was 1.16 (1.13-1.20). After further adjustment for confounders of center, year of visit, smoking status, alcohol intake, regular exercise, education level, and body mass index, the association between NAFLD and incident reflux esophagitis was attenuated, but remained significant (aHR 1.06; 95% CI 1.02-1.10). In this large cohort of Korean men and women, participants with NAFLD exhibited increased incidence of reflux esophagitis independent of possible confounders, suggesting that NAFLD contributes to the development of reflux esophagitis.

Oral Fructose Absorption in Obese Children with Non-Alcoholic Fatty Liver Disease

PubMed Central

Sullivan, Jillian S; Le, MyPhuong T; Pan, Zhaoxing; Rivard, Christopher; Love-Osborne, Kathryn; Robbins, Kristen; Johnson, Richard J; Sokol, Ronald J; Sundaram, Shikha S

2014-01-01

Background Fructose intake is associated with NAFLD (Non-Alcoholic Fatty Liver Disease) development. Objective To measure fructose absorption/metabolism in pediatric NAFLD compared to obese and lean controls. Methods Children with histologically proven NAFLD, and obese and lean controls received oral fructose (1 gm/kg ideal body weight). Serum glucose, insulin, uric acid, and fructose, urine uric acid, urine fructose, and breath hydrogen levels were measured at baseline and multiple points until 360 minutes after fructose ingestion. Results Nine NAFLD (89% Hispanic, mean age 14.3 years, mean BMI 35.3 kg/m2), 6 Obese Controls (67% Hispanic, mean age 12.7 years, mean BMI 31.0 kg/m2), and 9 Lean Controls (44% Hispanic, mean age 14.3 years, mean BMI 19.4 kg/m2) were enrolled. Following fructose ingestion, NAFLD vs. Lean Controls had elevated serum glucose, insulin, and uric acid (p<0.05), higher urine uric acid (p=0.001) but lower fructose excretion (p=0.002) and lower breath hydrogen 180-min AUC (p=0.04). NAFLD vs. Obese Controls had similar post-fructose serum glucose, insulin, urine uric acid, and breath hydrogen, but elevated serum uric acid (p<0.05) and lower urine fructose excretion (p=0.02). Conclusions Children with NAFLD absorb and metabolize fructose more effectively than lean subjects, associated with an exacerbated metabolic profile following fructose ingestion. PMID:24961681

The association between EMS workplace safety culture and safety outcomes.

PubMed

Weaver, Matthew D; Wang, Henry E; Fairbanks, Rollin J; Patterson, Daniel

2012-01-01

Prior studies have highlighted wide variation in emergency medical services (EMS) workplace safety culture across agencies. To determine the association between EMS workplace safety culture scores and patient or provider safety outcomes. We administered a cross-sectional survey to EMS workers affiliated with a convenience sample of agencies. We recruited these agencies from a national EMS management organization. We used the EMS Safety Attitudes Questionnaire (EMS-SAQ) to measure workplace safety culture and the EMS Safety Inventory (EMS-SI), a tool developed to capture self-reported safety outcomes from EMS workers. The EMS-SAQ provides reliable and valid measures of six domains: safety climate, teamwork climate, perceptions of management, working conditions, stress recognition, and job satisfaction. A panel of medical directors, emergency medical technicians and paramedics, and occupational epidemiologists developed the EMS-SI to measure self-reported injury, medical errors and adverse events, and safety-compromising behaviors. We used hierarchical linear models to evaluate the association between EMS-SAQ scores and EMS-SI safety outcome measures. Sixteen percent of all respondents reported experiencing an injury in the past three months, four of every 10 respondents reported an error or adverse event (AE), and 89% reported safety-compromising behaviors. Respondents reporting injury scored lower on five of the six domains of safety culture. Respondents reporting an error or AE scored lower for four of the six domains, while respondents reporting safety-compromising behavior had lower safety culture scores for five of the six domains. Individual EMS worker perceptions of workplace safety culture are associated with composite measures of patient and provider safety outcomes. This study is preliminary evidence of the association between safety culture and patient or provider safety outcomes.

A new Em-like protein from Lactuca sativa, LsEm1, enhances drought and salt stress tolerance in Escherichia coli and rice.

PubMed

Xiang, Dian-Jun; Man, Li-Li; Zhang, Chun-Lan; Peng-Liu; Li, Zhi-Gang; Zheng, Gen-Chang

2018-02-07

Late embryogenesis abundant (LEA) proteins are closely related to abiotic stress tolerance of plants. In the present study, we identified a novel Em-like gene from lettuce, termed LsEm1, which could be classified into group 1 LEA proteins, and shared high homology with Cynara cardunculus Em protein. The LsEm1 protein contained three different 20-mer conserved elements (C-element, N-element, and M-element) in the C-termini, N-termini, and middle-region, respectively. The LsEm1 mRNAs were accumulated in all examined tissues during the flowering and mature stages, with a little accumulation in the roots and leaves during the seedling stage. Furthermore, the LsEm1 gene was also expressed in response to salt, dehydration, abscisic acid (ABA), and cold stresses in young seedlings. The LsEm1 protein could effectively reduce damage to the lactate dehydrogenase (LDH) and protect LDH activity under desiccation and salt treatments. The Escherichia coli cells overexpressing the LsEm1 gene showed a growth advantage over the control under drought and salt stresses. Moreover, LsEm1-overexpressing rice seeds were relatively sensitive to exogenously applied ABA, suggesting that the LsEm1 gene might depend on an ABA signaling pathway in response to environmental stresses. The transgenic rice plants overexpressing the LsEm1 gene showed higher tolerance to drought and salt stresses than did wild-type (WT) plants on the basis of the germination performances, higher survival rates, higher chlorophyll content, more accumulation of soluble sugar, lower relative electrolyte leakage, and higher superoxide dismutase activity under stress conditions. The LsEm1-overexpressing rice lines also showed less yield loss compared with WT rice under stress conditions. Furthermore, the LsEm1 gene had a positive effect on the expression of the OsCDPK9, OsCDPK13, OsCDPK15, OsCDPK25, and rab21 (rab16a) genes in transgenic rice under drought and salt stress conditions, implying that overexpression of these

7 CFR 1945.35 - Special EM loan training.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) PROGRAM REGULATIONS (CONTINUED) EMERGENCY Disaster Assistance-General § 1945.35 Special EM loan training... workshop and a test. (c) Objective. The basic objective of this training program is to keep State and... employees in administering the EM loan program. (d) Comprehensive EM loan training package. A comprehensive...

The association between EMS workplace safety culture and safety outcomes

PubMed Central

Weaver, Matthew D.; Wang, Henry E.; Fairbanks, Rollin J.; Patterson, Daniel

2012-01-01

Objective Prior studies have highlighted wide variation in EMS workplace safety culture across agencies. We sought to determine the association between EMS workplace safety culture scores and patient or provider safety outcomes. Methods We administered a cross-sectional survey to EMS workers affiliated with a convenience sample of agencies. We recruited these agencies from a national EMS management organization. We used the EMS Safety Attitudes Questionnaire (EMS-SAQ) to measure workplace safety culture and the EMS Safety Inventory (EMS-SI), a tool developed to capture self-reported safety outcomes from EMS workers. The EMS-SAQ provides reliable and valid measures of six domains: safety climate, teamwork climate, perceptions of management, perceptions of working conditions, stress recognition, and job satisfaction. A panel of medical directors, paramedics, and occupational epidemiologists developed the EMS-SI to measure self-reported injury, medical errors and adverse events, and safety-compromising behaviors. We used hierarchical linear models to evaluate the association between EMS-SAQ scores and EMS-SI safety outcome measures. Results Sixteen percent of all respondents reported experiencing an injury in the past 3 months, four of every 10 respondents reported an error or adverse event (AE), and 90% reported safety-compromising behaviors. Respondents reporting injury scored lower on 5 of the 6 domains of safety culture. Respondents reporting an error or AE scored lower for 4 of the 6 domains, while respondents reporting safety-compromising behavior had lower safety culture scores for 5 of 6 domains. Conclusions Individual EMS worker perceptions of workplace safety culture are associated with composite measures of patient and provider safety outcomes. This study is preliminary evidence of the association between safety culture and patient or provider safety outcomes. PMID:21950463