Outcomes of Liver Transplant Recipients With Model for End-Stage Liver Disease Exception: Single-Center Experience in the Northeast of Brazil.

PubMed

Coelho, G R; Praciano, A M; Viana, G N R; Lima, C A; Feitosa Neto, B A; Garcia, J H P

2018-06-01

The Model for End-Stage Liver Disease (MELD) exception policy in liver transplantation is based on symptoms and clinical conditions not included in the calculated MELD score. Therefore, patients with chronic liver disease, like refractory ascites, chronic encephalopathy, recurrent cholangitis, and refractory pruritus, may benefit with extra points. The objective of this study was to establish the profile of the patients submitted to liver transplantation with MELD exceptions based on symptoms in the University Hospital Walter Cantídio, Ceara, Brazil, between the years of 2012 and 2015, analyzing donor and recipient data, with special attention to patients with refractory ascites and recurrent encephalopathy, including survival rates. The results demonstrated acceptable survival rates for MELD exception patients (78.4% in 3 years), showing that maybe this allocation criterion should be maintained, or even expanded. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular characterization of occult hepatitis B virus infection in patients with end-stage liver disease in Colombia

PubMed Central

Rendon, Julio Cesar; Cortes-Mancera, Fabian; Restrepo-Gutierrez, Juan Carlos; Hoyos, Sergio

2017-01-01

Background Hepatitis B virus (HBV) occult infection (OBI) is a risk factor to be taken into account in transfusion, hemodialysis and organ transplantation. The aim of this study was to identify and characterize at the molecular level OBI cases in patients with end-stage liver disease. Methods Sixty-six liver samples were obtained from patients with diagnosis of end-stage liver disease submitted to liver transplantation in Medellin (North West, Colombia). Samples obtained from patients who were negative for the surface antigen of HBV (n = 50) were tested for viral DNA detection by nested PCR for ORFs S, C, and X and confirmed by Southern-Blot. OBI cases were analyzed by sequencing the viral genome to determine the genotype and mutations; additionally, viral genome integration events were examined by the Alu-PCR technique. Results In five cases out of 50 patients (10%) the criteria for OBI was confirmed. HBV genotype F (subgenotypes F1 and F3), genotype A and genotype D were characterized in liver samples. Three integration events in chromosomes 5q14.1, 16p13 and 20q12 affecting Receptor-type tyrosine-protein phosphatase T, Ras Protein Specific Guanine Nucleotide Releasing Factor 2, and the zinc finger 263 genes were identified in two OBI cases. Sequence analysis of the viral genome of the 5 OBI cases showed several punctual missense and nonsense mutations affecting ORFs S, P, Core and X. Conclusions This is the first characterization of OBI in patients with end-stage liver disease in Colombia. The OBI cases were identified in patients with HCV infection or cryptogenic cirrhosis. The integration events (5q14.1, 16p13 and 20q12) described in this study have not been previously reported. Further studies are required to validate the role of mutations and integration events in OBI pathogenesis. PMID:28686707

Alcoholic Liver Disease: Pathogenesis and Current Management

PubMed Central

Osna, Natalia A.; Donohue, Terrence M.; Kharbanda, Kusum K.

2017-01-01

Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease. PMID:28988570

Outcome after associating liver partition and portal vein ligation for staged hepatectomy and conventional two-stage hepatectomy for colorectal liver metastases.

PubMed

Adam, R; Imai, K; Castro Benitez, C; Allard, M-A; Vibert, E; Sa Cunha, A; Cherqui, D; Baba, H; Castaing, D

2016-10-01

Although associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been increasingly adopted by many centres, the oncological outcome for colorectal liver metastases compared with that after two-stage hepatectomy is still unknown. Between January 2010 and June 2014, all consecutive patients who underwent either ALPPS or two-stage hepatectomy for colorectal liver metastases in a single institution were included in the study. Morbidity, mortality, disease recurrence and survival were compared. The two groups were comparable in terms of clinicopathological characteristics. ALPPS was completed in all 17 patients, whereas the second-stage hepatectomy could not be completed in 15 of 41 patients. Ninety-day mortality rates for ALPPS and two-stage resection were 0 per cent (0 of 17) versus 5 per cent (2 of 41) (P = 0·891). Major complication rates (Clavien grade at least III) were 41 per cent (7 of 17) and 39 per cent (16 of 41) respectively (P = 0·999). Overall survival was significantly lower after ALPPS than after two-stage hepatectomy: 2-year survival 42 versus 77 per cent respectively (P = 0·006). Recurrent disease was more often seen in the liver in the ALPPS group. Salvage surgery was less often performed after ALPPS (2 of 8 patients) than after two-stage hepatectomy (10 of 17). Although major complication and 90-day mortality rates of ALPPS were similar to those of two-stage hepatectomy, overall survival was significantly lower following ALPPS. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Assessment of Liver Fibrosis by Transient Elastography Should Be Done After Hemodialysis in End Stage Renal Disease Patients with Liver Disease.

PubMed

Taneja, Sunil; Borkakoty, Amritangsu; Rathi, Sahaj; Kumar, Vivek; Duseja, Ajay; Dhiman, Radha K; Gupta, Krishan L; Chawla, Yogesh

2017-11-01

The patients with end stage renal disease (ESRD) are at greater risk of acquiring chronic hepatitis B or C and subsequently development of liver disease. The aim of the study was to assess liver fibrosis by transient elastography (TE) and look for factors associated with change in liver stiffness measurement (LSM) with one session of hemodialysis (HD). Consecutive ESRD patients on maintenance hemodialysis (MHD) with suspected liver disease were enrolled. They underwent LSM by TE before and after one session of HD. Bioelectric impedance analysis was done to evaluate the volume status at the time of TE. Sixty-eight patients with mean age of 40 ± 14 years were included. There was a significant reduction in LSM after HD (18.5 [95% CI 14.8-23.1] vs. 11.2 [95% CI 8.8-13.7] kPa, p < 0.001), with a mean LSM reduction of 7.2 [95% CI 5.25-9.19] kPa. On stratification in two groups by net ultrafiltration during HD (> or < 2.5 liters [L]), change in LSM was substantially higher in patients when total fluid removed was > 2.5 L (8.6 [95% CI 5.7-11.5] vs. 5.1 [95% CI 2.9-7.5], p = 0.05). In 18 patients who underwent liver biopsy, LSM after HD performed better at detecting significant fibrosis, with area under receiver operating characteristics curve 0.71 [95% CI 0.46-0.97], versus 0.64 [95% CI 0.38-0.90], respectively. An LSM value of 12.2 kPa after HD was 71% sensitive and 74% specific for detection of significant fibrosis (≥ F2), while values less than 9 kPa ruled out significant fibrosis with a sensitivity and specificity of 37 and 100%, respectively. LSM by TE decreases significantly after HD in patients with ESRD on long-term MHD. Hence, TE should be done after HD for accurate assessment of liver fibrosis.

Staging Liver Fibrosis with Statistical Observers

NASA Astrophysics Data System (ADS)

Brand, Jonathan Frieman

Chronic liver disease is a worldwide health problem, and hepatic fibrosis (HF) is one of the hallmarks of the disease. Pathology diagnosis of HF is based on textural change in the liver as a lobular collagen network that develops within portal triads. The scale of collagen lobules is characteristically on order of 1mm, which close to the resolution limit of in vivo Gd-enhanced MRI. In this work the methods to collect training and testing images for a Hotelling observer are covered. An observer based on local texture analysis is trained and tested using wet-tissue phantoms. The technique is used to optimize the MRI sequence based on task performance. The final method developed is a two stage model observer to classify fibrotic and healthy tissue in both phantoms and in vivo MRI images. The first stage observer tests for the presence of local texture. Test statistics from the first observer are used to train the second stage observer to globally sample the local observer results. A decision of the disease class is made for an entire MRI image slice using test statistics collected from the second observer. The techniques are tested on wet-tissue phantoms and in vivo clinical patient data.

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease

PubMed Central

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-01-01

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current “gold standard” for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence. PMID:26494961

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease.

PubMed

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-10-21

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

Autoimmune liver disease 2007.

PubMed

Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

2008-01-01

Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

Cirrhosis and autoimmune liver disease: Current understanding

PubMed Central

Liberal, Rodrigo; Grant, Charlotte R

2016-01-01

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.

PubMed

Stål, Per

2015-10-21

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

Liver fibrosis markers in alcoholic liver disease.

PubMed

Chrostek, Lech; Panasiuk, Anatol

2014-07-07

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

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

Impact of the severity of end-stage liver disease in cardiac structure and function.

PubMed

Silvestre, Odilson Marcos; Bacal, Fernando; de Souza Ramos, Danusa; Andrade, Jose L; Furtado, Meive; Pugliese, Vincenzo; Belleti, Elisangela; Andraus, Wellington; Carrilho, Flair José; Carneiro D'Albuquerque, Luiz Augusto; Queiroz Farias, Alberto

2013-01-01

The impact of end-stage liver disease (ESLD) in cardiac remodeling of patients with cirrhosis is unknown. Our aim was to correlate the severity of ESLD with morphologic and functional heart changes. 184 patients underwent a protocol providing data on the severity of ESLD and undergoing echocardiography to assess the diameters of the left atrium and right ventricle; the systolic and diastolic diameters of the left ventricle, interventricular septum, and posterior wall of the left ventricle; systolic pulmonary artery pressure; ejection fraction; and diastolic function. Severity of ESLD was assessed by the Model for End-Stage Liver Disease (MELD) score. Left-atrial diameter (r = 0.323; IC 95% 0.190-0.455; p < 0.001), left-ventricular diastolic diameter (r = 0.177; IC 95% 0.033-0.320; p = 0.01) and systolic pulmonary artery pressure (r = 0.185; IC 95% 0.036-0.335; p = 0.02) significantly correlated with MELD score. Patients with MELD ≥ 16 had significantly higher left-atrial diameter and systolic pulmonary artery pressure, compared with patients with MELD scores < 16 points. Changes in cardiac structure and function correlate with the severity of ESLD.

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

PubMed

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

2013-04-01

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

Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance

PubMed Central

Stål, Per

2015-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD. PMID:26494963

A simplified multivisceral transplantation procedure for patients with combined end-stage liver disease and type 2 diabetes mellitus.

PubMed

He, Xiao-Shun; Fu, Shun-Jun; Zhao, Qiang; Zhu, Xiao-Feng; Wang, Dong-Ping; Han, Ming; Ju, Wei-Qiang; Ma, Yi; Jiao, Xing-Yuan; Yuan, Xiao-Peng; Hu, An-Bin; Guo, Zhi-Yong

2017-09-01

In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Stage scoring of liver fibrosis using Mueller matrix microscope

NASA Astrophysics Data System (ADS)

Zhou, Jialing; He, Honghui; Wang, Ye; Ma, Hui

2016-10-01

Liver fibrosis is a common pathological process of varied chronic liver diseases including alcoholic hepatitis, virus hepatitis, and so on. Accurate evaluation of liver fibrosis is necessary for effective therapy and a five-stage grading system was developed. Currently, experienced pathologists use stained liver biopsies to assess the degree of liver fibrosis. But it is difficult to obtain highly reproducible results because of huge discrepancy among different observers. Polarization imaging technique has the potential of scoring liver fibrosis since it is capable of probing the structural and optical properties of samples. Considering that the Mueller matrix measurement can provide comprehensive microstructural information of the tissues, in this paper, we apply the Mueller matrix microscope to human liver fibrosis slices in different fibrosis stages. We extract the valid regions and adopt the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters for quantitative analysis. We also use the Monte Carlo simulation to analyze the relationship between the microscopic Mueller matrix parameters and the characteristic structural changes during the fibrosis process. The experimental and Monte Carlo simulated results show good consistency. We get a positive correlation between the parameters and the stage of liver fibrosis. The results presented in this paper indicate that the Mueller matrix microscope can provide additional information for the detections and fibrosis scorings of liver tissues and has great potential in liver fibrosis diagnosis.

End-Stage Liver Disease in Patients with Intracranial Hemorrhage Is Associated with Increased Mortality: A Cohort Study.

PubMed

Lagman, Carlito; Nagasawa, Daniel T; Sheppard, John P; Jacky Chen, Cheng Hao; Nguyen, Thien; Prashant, Giyarpuram N; Niu, Tianyi; Tucker, Alexander M; Kim, Won; Pouratian, Nader; Kaldas, Fady M; Busuttil, Ronald W; Yang, Isaac

2018-05-01

To determine if end-stage liver disease (ESLD) in patients with intracranial hemorrhage (ICH) is associated with increased mortality. This single-center, retrospective cohort study included 53 patients (33 in ESLD cohort and 20 in non-ESLD cohort) who received neurosurgical care between 2006 and 2017. ESLD was defined clinically as severely impaired liver function and at least 1 major complication of liver failure. The primary outcome was mortality. Overall, in-hospital, and 30-day mortality rates were higher in the ESLD cohort versus the non-ESLD cohort (79 vs. 30%, 79 vs. 20%, and 64 vs. 25%, all P ≤ 0.01). We identified a significant difference in overall survival between ESLD and non-ESLD cohorts on Kaplan-Meier analysis (P = 0.004 with log-rank and Wilcoxon tests). Odds of overall, in-hospital, and 30-day mortality in the ESLD cohort were 8.67 (95% confidence interval [CI], 2.44-30.84), 14.86 (95% CI, 3.75-58.90), and 5.25 (95% CI, 1.53-18.08). Other predictors of overall mortality included primary admission diagnosis of liver disease (odds ratio [OR] = 9.60; 95% CI, 3.75-58.90), higher Child-Pugh (OR = 1.64; 95% CI, 2.66-34.67) and Model for End-Stage Liver Disease (OR = 1.12; 95% CI, 1.04-1.20) scores, lower Glasgow Coma Scale score (OR = 0.73; 95% CI, 0.61-0.88), ICH that developed in the hospital (OR = 4.11; 95% CI, 1.21-13.98), and intraparenchymal hemorrhage (OR = 9.23; 95% CI, 1.72-49.56). ESLD in patients with ICH is associated with increased mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

Etiology and Viral Genotype in Patients with End-Stage Liver Diseases admitted to a Hepatology Unit in Colombia

PubMed Central

Cortes-Mancera, Fabian; Loureiro, Carmen Luisa; Hoyos, Sergio; Restrepo, Juan-Carlos; Correa, Gonzalo; Jaramillo, Sergio; Norder, Helene; Pujol, Flor Helene; Navas, Maria-Cristina

2011-01-01

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the principal risk factor associated to end-stage liver diseases in the world. A study was carried out on end-stage liver disease cases admitted to an important hepatology unit in Medellin, the second largest city in Colombia. From 131 patients recruited in this prospective study, 71% of cases were diagnosed as cirrhosis, 12.2% as HCC, and 16.8% as cirrhosis and HCC. Regarding the risk factors of these patients, alcohol consumption was the most frequent (37.4%), followed by viral etiology (17.6%). Blood and/or hepatic tissue samples from patients with serological markers for HCV or HBV infection were characterized; on the basis of the phylogenetic analysis of HCV 5′ UTR and HBV S gene, isolates belonged to HCV/1 and HBV/F3, respectively. These results confirm the presence of strains associated with poor clinical outcome, in patients with liver disease in Colombia; additionally, HBV basal core promoter double mutant was identified in HCC cases. Here we show the first study of cirrhosis and/or HCC in Colombian and HBV and HCV molecular characterization of these patients. Viral aetiology was not the main risk factor in this cohort but alcohol consumption. PMID:21941645

Reduced neural baroreflex sensitivity is related to enhanced endothelial function in patients with end-stage liver disease.

PubMed

Sárközi, Adrienn; Cseh, Domonkos; Gerlei, Zsuzsanna; Kollai, Márk

2018-02-01

Reduced baroreflex sensitivity (BRS) is a frequent complication in end-stage liver disease, but the underlying mechanism is unknown. We investigated the mechanical and neural components of BRS. Increased nitric oxide (NO) production has been reported in end-stage liver failure. Based on earlier experiments, we hypothesised that enhanced endothelial function might affect baroreflex function. Therefore, we explored the relation between endothelial function and the components of BRS. We enrolled 24 patients and 23 controls. BRS was determined by the spontaneous sequence method. Mechanical component was characterised by the distensibility coefficient (DC) of common carotid artery. Neural component was estimated as the ratio of integrated BRS and DC. Endothelial function was quantified by flow-mediated dilation (FMD) of the brachial artery. Integrated BRS was reduced in patients [7.00 (5.80-9.25) vs. 11.1 (8.50-14.80) ms/mmHg]. The mechanical component was not different in the two groups, whereas neural component showed significant reduction in patients (3.54 ± 1.20 vs. 4.48 ± 1.43 ms/10 -3 ). FMD was higher in patients (9.81 ± 3.77 vs. 5.59 ± 1.36%). FMD and neural BRS were directly related in controls (r = 0.62), but inversely related in patients (r = -0.49). Baroreflex impairment in end-stage liver disease might be explained by deterioration of the neural component, while the mechanical component appears to be preserved. Endothelial NO may enhance BRS in health; however, central endothelial overproduction of NO likely contributes to the reduction of neural component of BRS in patients awaiting liver transplantation.

Recurrent viral liver disease (hepatitis B and C) after liver transplantation.

PubMed

Olivera-Martínez, Marco Antonio; Gallegos-Orozco, Juan F

2007-08-01

Hepatitis C represents more than 35% of liver transplant candidates worldwide. Meanwhile, hepatitis B continues to be an important cause of end-stage liver disease and hepatocellular carcinoma in Asia and Africa. Recurrent viral liver disease is a significant event after liver transplantation and continues to be one of the main causes of graft dysfunction and loss in the middle and long-term follow-up. Mechanisms of liver reinfection and disease recurrence vary between these two viruses and pre-emptive as well as the therapeutic approaches are different. Hepatitis B patients can be managed with immune globulin immediately after liver transplant and various agents such as nucleotide and nucleoside analogues can be associated. As a result, disease recurrence has been delayed or prevented in these patients. Individuals transplanted for hepatitis C are known to have universal reinfection and a high rate of disease recurrence has been reported in the literature. Strategies to treat hepatitis C recurrence are limited to the use of pegylated interferon and ribavirin when disease is demonstrated histologically and biochemically, although other strategies have been described with limited or no success. We herein review the mechanisms of disease recurrence and the current as well as the future therapeutic approaches to prevent and to treat these diseases.

Association Between Obesity and Discordance in Fibrosis Stage Determination by Magnetic Resonance vs Transient Elastography in Patients With Nonalcoholic Liver Disease.

PubMed

Caussy, Cyrielle; Chen, Jun; Alquiraish, Mosab H; Cepin, Sandra; Nguyen, Phirum; Hernandez, Carolyn; Yin, Meng; Bettencourt, Ricki; Cachay, Edward R; Jayakumar, Saumya; Fortney, Lynda; Hooker, Jonathan; Sy, Ethan; Valasek, Mark A; Rizo, Emily; Richards, Lisa; Brenner, David A; Sirlin, Claude B; Ehman, Richard L; Loomba, Rohit

2018-01-17

Magnetic resonance elastography (MRE) and transient elastography (TE) are noninvasive techniques used to detect liver fibrosis in nonalcoholic fatty liver disease. MRE detects fibrosis more accurately than TE, but MRE is more expensive, and the concordance between MRE and TE have not been optimally assessed in obese patients. It is important to determine under which conditions TE and MRE produce the same readings, so that some patients can simply undergo TE evaluation to detect fibrosis. We aimed to assess the association between body mass index (BMI) and discordancy between MRE and TE findings, using liver biopsy as the reference, and validated our findings in a separate cohort. We performed a cross-sectional study of 119 adults with nonalcoholic fatty liver disease who underwent MRE, TE with M and XL probe, and liver biopsy analysis from October 2011 through January 2017 (training cohort). MRE and TE results were considered to be concordant if they found patients to have the same stage fibrosis as liver biopsy analysis. We validated our findings in 75 adults with nonalcoholic fatty liver disease who underwent contemporaneous MRE, TE, and liver biopsy at a separate institution from March 2010 through May 2013. The primary outcome was rate of discordance between MRE and TE in determining stage of fibrosis (stage 2-4 vs 0-1). Secondary outcomes were the rate of discordance between MRE and TE in determining dichotomized stage of fibrosis (1-4 vs 0, 3-4 vs 0-2, and 4 vs 0-3). In the training cohort, there was 43.7% discordance in findings from MRE versus TE. BMI associated significantly with discordance in findings from MRE versus TE (odds ratio, 1.69; 95% confidence interval, 1.15-2.51; P = .008) after multivariable adjustment by age and sex. The findings were confirmed in the validation cohort: there was 45.3% discordance in findings from MRE versus TE. BMI again associated significantly with discordance in findings from MRE versus TE (odds ratio, 1.52; 95

United Network for Organ Sharing regional variations in appeal denial rates with non-standard Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exceptions: support for a national review board.

PubMed

Gish, Robert G; Wong, Robert J; Honerkamp-Smith, Gordon; Xu, Ronghui; Osorio, Robert W

2015-06-01

Although it has been generally recognized that there are inconsistencies among Regional Review Boards in the assignment of points for model for end-stage liver disease (MELD)/pediatric end-stage liver disease (PELD) exception patients with resulting considerable variation in appeal denial rates, data to actually prove this have been limited. We reviewed 6533 MELD/PELD exception applications submitted between 2005 and 2008, calculated the variation in approval/denial rates, and followed these cases through mid-2013 to assess the effects on patient outcomes. We found highly significant regional variations in denial rates for appeals by exception patients and in transplantation rates. The odds of transplant for patients whose appeals are approved is 2.45 times that of patients not approved; that this effect does not vary by region suggests that the variation in transplant rates is driven, at least in part, by the variation in appeal denial rates. Health deterioration or death accounts for more than two-thirds of wait list removals among patients removed for reasons other than transplant. Our findings add to the weight of evidence that a national review board that uses current clinical expertise, peer review literature, and data to consistently assign priority could reduce regional inequities and move toward equitable allocation of organs and compliance with the United States Department of Health & Human Services Final Rule. © 2015 The Authors. Clinical Transplantation. Published by John Wiley & Sons Ltd.

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage.

PubMed

Camus, Marine; Jensen, Dennis M; Matthews, Jason D; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S

2014-10-14

To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT.

Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice

PubMed Central

Mikolajczak, Sebastian A.; Vaughan, Ashley M.; Kangwanrangsan, Niwat; Roobsoong, Wanlapa; Fishbaugher, Matthew; Yimamnuaychok, Narathatai; Rezakhani, Nastaran; Lakshmanan, Viswanathan; Singh, Naresh; Kaushansky, Alexis; Camargo, Nelly; Baldwin, Michael; Lindner, Scott E.; Adams, John H.; Prachumsri, Jetsumon; Kappe, Stefan H.I.

2017-01-01

Plasmodium vivax malaria is characterized by periodic relapses of symptomatic blood stage parasite infections likely initiated by activation of dormant liver stage parasites -hypnozoites. The lack of tractable animal models for P. vivax constitutes a severe obstacle to investigate this unique aspect of its biology and to test drug efficacy against liver stages. We show that the FRG KO huHep liver-humanized mice support P. vivax sporozoite infection, development of liver stages, and the formation of small non-replicating hypnozoites. Cellular characterization of P. vivax liver stage development in vivo demonstrates complete maturation into infectious exo-erythrocytic merozoites and continuing persistence of hypnozoites. Primaquine prophylaxis or treatment prevents and eliminates liver stage infection. Thus, the P. vivax/FRG KO huHep mouse infection model constitutes an important new tool to investigate the biology of liver stage development and dormancy and might aid in the discovery of new drugs for the prevention of relapsing malaria. PMID:25800544

Palliative Care and Health Care Utilization for Patients With End-Stage Liver Disease at the End of Life.

PubMed

Patel, Arpan A; Walling, Anne M; Ricks-Oddie, Joni; May, Folasade P; Saab, Sammy; Wenger, Neil

2017-10-01

There has been increased attention on ways to improve the quality of end-of-life care for patients with end-stage liver disease; however, there have been few reports of care experiences for patients during terminal hospitalizations. We analyzed data from a large national database to increase our understanding of palliative care for and health care utilization by patients with end-stage liver disease. We performed a cross-sectional, observational study to examine terminal hospitalizations of adults with decompensated cirrhosis using data from the National Inpatient Sample from 2009 through 2013. We collected data on palliative care consultation and total hospital costs, and performed multivariate regression analyses to identify factors associated with palliative care consultation. We also investigated whether consultation was associated with lower costs. Among hospitalized adults with terminal decompensated cirrhosis, 30.3% received palliative care; the mean cost per hospitalization was $48,551 ± $1142. Palliative care consultation increased annually, and was provided to 18.0% of patients in 2009 and to 36.6% of patients in 2013 (P < .05). The mean cost for the terminal hospitalization did not increase significantly ($47,969 in 2009 to $48,956 in 2013, P = .77). African Americans, Hispanics, Asians, and liver transplant candidates were less likely to receive palliative care, whereas care in large urban teaching hospitals was associated with a higher odds of receiving consultation. Palliative care was associated with lower procedure burden-after adjusting for other factors, palliative care was associated with a cost reduction of $10,062. Palliative care consultation for patients with end-stage liver disease increased from 2009 through 2013. Palliative care consultation during terminal hospitalizations is associated with lower costs and procedure burden. Future research should evaluate timing and effects of palliative care on quality of end-of-life care in this

Dialysis-dependent acute kidney injury in children with end-stage liver disease: prevalence, dialysis modalities and outcome.

PubMed

Kreuzer, Martin; Gähler, Dagmar; Rakenius, Annette C; Prüfe, Jenny; Jack, Thomas; Pfister, Eva-Doreen; Pape, Lars

2015-12-01

Acute kidney injury (AKI) is a major complication in children with hepatic failure which leads to increased morbidity and mortality. The aim of this study was to provide paediatric data on the prevalence of dialysis-dependent AKI (dAKI), the feasibility and efficacy of dialysis methods and outcome. We conducted a retrospective analysis of 367 children listed for orthotopic liver transplantation (OLT) in our centre during the past decade. Data on 30 children (15 boys, 15 girls) were compiled for retrospective analysis, and data on dialysis feasibility and efficacy were available for 26 of these. Median age was 3.5 (range 0.4-17.7) years. Median MELD (Model For End-Stage Liver Disease) score was 33. dAKI was caused by hepato-renal syndrome in 16 of the 30 children. Twenty-one patients were treated with continuous veno-venous haemofiltration (CVVH), and nine patients received peritoneal dialysis (PD). Overall mortality was 77%. Mortality within the PD-group was 100 % versus 67% in the CVVH-group (p = 0.039). Urea reduction rate within the first 24 h of treatment was 12.9% in the PD group and 23.5% in the CVVH group (p = 0.019). Children with end-stage liver disease have a high risk for dAKI associated with high mortality. CVVH is associated with better efficacy and less mortality than PD.

Evaluation of Acoustic Radiation Force Impulse (ARFI) for Fibrosis Staging in Chronic Liver Diseases.

PubMed

Gani, Rino Alvani; Hasan, Irsan; Sanityoso, Andri; Lesmana, Cosmas Rinaldi A; Kurniawan, Juferdy; Jasirwan, Chyntia Olivia Maurine; Kalista, Kemal Fariz; Lutfie, Lutfie

2017-04-01

acoustic radiation force impulse (ARFI) is a new proposed noninvasive method for liver fibrosis staging. Integrated with B-mode ultrasonography, ARFI can be used to assess liver tissue condition. However its diagnostic accuracy is still being continuously evaluated. Also, there is lack of data regarding the utilization of ARFI in our population. This study aimed to evaluate the diagnostic value of ARFI as an alternative noninvasive modality for fibrosis staging in chronic hepatitis B and hepatitis C patients in our population. we conducted cross-sectional comparison of ARFI imaging and transient elastography on patients who underwent liver biopsy at Cipto Mangunkusumo Hospital. Fibrosis staging using METAVIR scoring system presented as standard reference. A total of 43 patients underwent liver biopsy was evaluated by ARFI imaging and transient elastography. Cut-off values were determined using receiver-operating characteristic (ROC). both liver stiffness determined by ARFI and transient elastography (TE) were moderately correlated with METAVIR score with value of 0.581 and 0.613, respectively (both P<0.01). Diagnostic accuracy of ARFI predicted significant fibrosis (F≥2) with area under receiver operating characteristic curve (AUROC) of 0.773 (95% CI 0.616-0.930) and even better for cirrhosis (F4 fibrosis), expressed as AUROC of 0.856 (95% CI 0.736-0.975). Transient elastography was better for significant fibrosis with AUROC of 0.761 (95% CI 0.601-0.920) and was best for prediction of cirrhosis, expressed as AUROC of 0.845 (95% CI 0.722-0.968). ARFI is provided with more convenient evaluation of liver tissue condition, and its diagnostic accuracy is not significantly different from TE for staging liver fibrosis.

Ascertainment and verification of end-stage renal disease and end-stage liver disease in the north american AIDS cohort collaboration on research and design.

PubMed

Kitahata, Mari M; Drozd, Daniel R; Crane, Heidi M; Van Rompaey, Stephen E; Althoff, Keri N; Gange, Stephen J; Klein, Marina B; Lucas, Gregory M; Abraham, Alison G; Lo Re, Vincent; McReynolds, Justin; Lober, William B; Mendes, Adell; Modur, Sharada P; Jing, Yuezhou; Morton, Elizabeth J; Griffith, Margaret A; Freeman, Aimee M; Moore, Richard D

2015-01-01

The burden of HIV disease has shifted from traditional AIDS-defining illnesses to serious non-AIDS-defining comorbid conditions. Research aimed at improving HIV-related comorbid disease outcomes requires well-defined, verified clinical endpoints. We developed methods to ascertain and verify end-stage renal disease (ESRD) and end-stage liver disease (ESLD) and validated screening algorithms within the largest HIV cohort collaboration in North America (NA-ACCORD). Individuals who screened positive among all participants in twelve cohorts enrolled between January 1996 and December 2009 underwent medical record review to verify incident ESRD or ESLD using standardized protocols. We randomly sampled 6% of contributing cohorts to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ESLD and ESRD screening algorithms in a validation subcohort. Among 43,433 patients screened for ESRD, 822 screened positive of which 620 met clinical criteria for ESRD. The algorithm had 100% sensitivity, 99% specificity, 82% PPV, and 100% NPV for ESRD. Among 41,463 patients screened for ESLD, 2,024 screened positive of which 645 met diagnostic criteria for ESLD. The algorithm had 100% sensitivity, 95% specificity, 27% PPV, and 100% NPV for ESLD. Our methods proved robust for ascertainment of ESRD and ESLD in persons infected with HIV.

Chronic Kidney Disease and Related Long-term Complications Following Liver Transplantation

PubMed Central

Sharma, Pratima; Bari, Khurram

2015-01-01

Liver transplantation (LT) is the standard of care for patients with decompensated cirrhosis. LT recipients have excellent short-term and long-term outcomes including patient and graft survival. Since the adoption of model for end-stage liver disease (MELD) - based allocation policy, the incidence of post-transplant end stage renal disease has risen significantly. Occurrence of stage 4 chronic kidney disease and end stage renal disease substantially increase the risk of post-transplant deaths. Since majority of late post-transplant mortality is due to non-hepatic post-transplant comorbidities, personalized care directed towards risk factor modification may further improve post-transplant survival. PMID:26311603

Immediate postoperative tracheal extubation in a liver transplant recipient with encephalopathy and the Mayo end-stage liver disease score of 41: A CARE-compliant case report revealed meaningful challenge in recovery after surgery (ERAS) for liver transplantation.

PubMed

Li, Jianbo; Wang, Chengdi; Chen, Nan; Song, Jiulin; Sun, Yan; Yao, Qin; Yan, Lunan; Yang, Jiayin

2017-11-01

Immediate postoperative tracheal extubation (IPTE) is one of the most important subject in recovery after surgery (ERAS) for liver transplantation. However, the criteria for IPTE is not uniform at present. We reported a successful IPTE in a liver transplant recipient with encephalopathy and a high Mayo end-stage liver disease (MELD) score of 41, which beyond the so-called criteria reported in the literature. The patient was 48-year-old man, admitted in September 2016 for end-stage liver cirrhosis secondary to hepatitis B. End-stage liver cirrhosis secondary to hepatitis B with encephalopathy and a high MELD score of 41. He was involved in our ERAS project and was extubated at the end of the liver transplantation in the operating room. As a result, the patient was not reintubated and had an excellent postoperative recovery, staying in intensive care unit (ICU) for just 2 days and discharged home on day 10. We believed IPTE in liver transplant recipients with severe liver dysfunction is a meaningful challenge in ERAS for liver transplantation. Our case and literature review suggest 3 things: IPTE in liver transplantation is generally feasible and safe; the encephalopathy or high MELD score should not be the only limiting factor; and a more systematic predicting system for IPTE in liver transplantation should be addressed in future studies. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Dilemmas across different overseas liver transplant stages: Taiwan transplant recipient families' perspectives.

PubMed

Chen, H-M; Hu, R-H; Shih, F-Jong; Shih, F-J

2012-03-01

This study aimed to explore the dilemmas of Taiwanese overseas liver transplant recipient families (OLTRF) across three overseas liver transplant (OLT) stages in Taiwan and Mainland China. An exploratory qualitative method was employed using a purposive sample of OLTRF, who received guided face-to-face, semistructured interviews. Data were subjected to content analysis. Nineteen OLTRF (15 female, 4 male) aged between 29 and 71 years (mean 55.1) for 19 patients with end-stage liver diseases were interviewed. OLT stages including predeparture stage (first stage), stay in China stage (second stage), and reentry to Taiwan stage (third stage). Ten kinds of dilemmas were encountered: (1) unable to get transplantation immediately (first to second stages); (2) dilemma of choosing overseas transplantation (first to second stages); (3) uncertainty about the transplantation outcomes (second to third stages); (4) care pressure (second to third stages); (5) poor diet adaptation (second to third stages); (6) lack of trust in the medical care quality (second stage); (7) worry about not fulfilling family responsibilities (second stage); (8) lack of information (all stages); (9) financial pressure (all stages); and (10) frustration when seeking medical care (all stages). Taiwanese OLTRF's perspectives of their dilemmas through the OLT process were first revealed in this study. Both Western and Eastern health professionals might be empowered by better understanding of OLTRF's living experiences and concerns during the stages of overseas liver transplantation. Copyright © 2012 Elsevier Inc. All rights reserved.

Magnetic resonance elastography is as accurate as liver biopsy for liver fibrosis staging.

PubMed

Morisaka, Hiroyuki; Motosugi, Utaroh; Ichikawa, Shintaro; Nakazawa, Tadao; Kondo, Tetsuo; Funayama, Satoshi; Matsuda, Masanori; Ichikawa, Tomoaki; Onishi, Hiroshi

2018-05-01

Liver MR elastography (MRE) is available for the noninvasive assessment of liver fibrosis; however, no previous studies have compared the diagnostic ability of MRE with that of liver biopsy. To compare the diagnostic accuracy of liver fibrosis staging between MRE-based methods and liver biopsy using the resected liver specimens as the reference standard. A retrospective study at a single institution. In all, 200 patients who underwent preoperative MRE and subsequent surgical liver resection were included in this study. Data from 80 patients were used to estimate cutoff and distributions of liver stiffness values measured by MRE for each liver fibrosis stage (F0-F4, METAVIR system). In the remaining 120 patients, liver biopsy specimens were obtained from the resected liver tissues using a standard biopsy needle. 2D liver MRE with gradient-echo based sequence on a 1.5 or 3T scanner was used. Two radiologists independently measured the liver stiffness value on MRE and two types of MRE-based methods (threshold and Bayesian prediction method) were applied. Two pathologists evaluated all biopsy samples independently to stage liver fibrosis. Surgically resected whole tissue specimens were used as the reference standard. The accuracy for liver fibrosis staging was compared between liver biopsy and MRE-based methods with a modified McNemar's test. Accurate fibrosis staging was achieved in 53.3% (64/120) and 59.1% (71/120) of patients using MRE with threshold and Bayesian methods, respectively, and in 51.6% (62/120) with liver biopsy. Accuracies of MRE-based methods for diagnoses of ≥F2 (90-91% [108-9/120]), ≥F3 (79-81% [95-97/120]), and F4 (82-85% [98-102/120]) were statistically equivalent to those of liver biopsy (≥F2, 79% [95/120], P ≤ 0.01; ≥F3, 88% [105/120], P ≤ 0.006; and F4, 82% [99/120], P ≤ 0.017). MRE can be an alternative to liver biopsy for fibrosis staging. 3. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1268-1275. © 2017

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage

PubMed Central

Camus, Marine; Jensen, Dennis M; Matthews, Jason D; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S

2014-01-01

AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). METHODS: This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. RESULTS: A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. CONCLUSION: Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT. PMID:25320538

The Effects of Physical Exercise on Fatty Liver Disease

PubMed Central

van der Windt, Dirk J.; Sud, Vikas; Zhang, Hongji; Tsung, Allan; Huang, Hai

2018-01-01

The increasing prevalence of obesity has made nonalcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the fastest increasing etiology of end-stage liver disease and hepatocellular carcinoma. Physical inactivity is related to the severity of fatty liver disease irrespective of body weight, supporting the hypothesis that increasing physical activity through exercise can improve fatty liver disease. This review summarizes the evidence for the effects of physical exercise on NAFLD and NASH. Several clinical trials have shown that both aerobic and resistance exercise reduce the hepatic fat content. From clinical and basic scientific studies, it is evident that exercise affects fatty liver disease through various pathways. Improved peripheral insulin resistance reduces the excess delivery of free fatty acids and glucose for free fatty acid synthesis to the liver. In the liver, exercise increases fatty acid oxidation, decreases fatty acid synthesis, and prevents mitochondrial and hepatocellular damage through a reduction of the release of damage-associated molecular patterns. In conclusion, physical exercise is a proven therapeutic strategy to improve fatty liver disease. PMID:29212576

Closure of ascites leaks with fibrin glue injection in patients with end-stage liver disease.

PubMed

Sadik, Karim W; Laibstain, Sarah; Northup, Patrick G; Kashmer, David; Schmitt, Timothy M; Bonatti, Hugo J R

2011-09-01

Ascites leaks (AL) in patients with end-stage liver disease (ESLD) are associated with significant morbidity and mortality regardless if they are medically or surgically managed. In a pilot study, 14 ESLD patients with AL underwent treatment with fibrin glue injection around the leak after failing conservative therapy. The end point of this study was the cessation of AL in the short term and the maintenance of a leak-free abdomen in the long term, allowing for medical optimization of the patients. Median age of the 10 men and 4 women was 50 (range 26-67) years. Underlying ESLDs were chronic hepatitis C (n=5), alcoholic LD (n=2), cryptogenic cirrhosis (n=2), and miscellaneous (n=5). There were six leaking incisions posthernia repair (three umbilical and three inguinal), two leaking/ruptured umbilical hernias, four leaking paracentesis sites, one leaking Jackson-Pratt (JP) drain canal, and one leaking laparoscopic trocar site. Average AL volume per day was 1000 (range 400-2000) mL. All leaks were immediately resolved with a 3-5 mL fibrin glue injection. Five recurred and required a second injection (four within 24 hours). Mental status improved in 7 patients (West Haven Criteria: grade II to I [n=6], grade III to I [n=1]). Median model of end-stage liver disease scores improved from 23 (range 8-33) to 20 (range 14-26). There were no infections, bleeds, or other injection-related complications. Average follow-up for these patients was 441.6 days (range 2-852). Five patients underwent liver transplant (LT) median 15 (range 4-270) days postinjection; 2 of them died. Another 3 patients died (2 from sepsis and 1 from metastatic cancer). Fibrin glue injection for the control of AL is a simple and safe bedside procedure that quickly controls AL, allowing for patient recovery in anticipation of further care.

Survival Outcomes After Intracranial Hemorrhage in Liver Disease.

PubMed

Lagman, Carlito; Nagasawa, Daniel T; Azzam, Daniel; Sheppard, John P; Chen, Cheng Hao Jacky; Ong, Vera; Nguyen, Thien; Prashant, Giyarpuram N; Niu, Tianyi; Tucker, Alexander M; Kim, Won; Kaldas, Fady M; Pouratian, Nader; Busuttil, Ronald W; Yang, Isaac

2018-05-15

Survival outcomes for patients with liver disease who suffer an intracranial hemorrhage (ICH) have not been thoroughly investigated. To understand survival outcomes for 3 groups: (1) patients with an admission diagnosis of liver disease (end-stage liver disease [ESLD] or non-ESLD) who developed an ICH in the hospital, (2) patients with ESLD who undergo either operative vs nonoperative management, and (3) patients with ESLD on the liver transplant waitlist who developed an ICH in the hospital. We retrospectively reviewed hospital charts from March 2006 through February 2017 of patients with liver disease and an ICH evaluated by the neurosurgery service at a single academic medical center. The primary outcome was survival. We included a total of 53 patients in this study. The overall survival for patients with an admission diagnosis of liver disease who developed an ICH (n = 29, 55%) in the hospital was 22%. Of those patients with an admission diagnosis of liver disease, 27 patients also had ESLD. Kaplan-Meier analysis found no significant difference in survival for ESLD patients (n = 33, 62%) according to operative status. There were 11 ESLD patients on the liver transplant waitlist. The overall survival for patients with ESLD on the liver transplant waitlist who suffered an in-hospital ICH (n = 7, 13%) was 14%. ICH in the setting of liver disease carries a grave prognosis. Also, a survival advantage for surgical hematoma evacuation in ESLD patients is not clear.

Liver disease

MedlinePlus

... Coccidioidomycosis Delta agent (hepatitis D) Drug-induced cholestasis Fatty liver disease Hemochromatosis Hepatitis A Hepatitis B Hepatitis C ... abscess Reye syndrome Sclerosing cholangitis Wilson disease Images Fatty liver, CT scan Liver with disproportional fattening, CT scan ...

Zebrafish: an important tool for liver disease research.

PubMed

Goessling, Wolfram; Sadler, Kirsten C

2015-11-01

As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Zebrafish: An Important Tool for Liver Disease Research

PubMed Central

Goessling, Wolfram; Sadler, Kirsten C.

2016-01-01

As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. PMID:26319012

Application of Induced Pluripotent Stem Cells in Liver Diseases

PubMed Central

Yu, Yue; Wang, Xuehao; Nyberg, Scott L.

2014-01-01

Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID:26858888

Transient elastography compared to liver biopsy and morphometry for predicting fibrosis in pediatric chronic liver disease: Does etiology matter?

PubMed Central

Behairy, Behairy El-Sayed; Sira, Mostafa Mohamed; Zalata, Khaled Refat; Salama, El-Sayed Ebrahem; Abd-Allah, Mohamed Ahmed

2016-01-01

AIM: To evaluate transient elastography (TE) as a noninvasive tool in staging liver fibrosis compared with liver biopsy and morphometry in children with different chronic liver diseases. METHODS: A total of 90 children [50 with chronic hepatitis C virus (HCV), 20 with autoimmune hepatitis (AIH) and 20 with Wilson disease] were included in the study and underwent liver stiffness measurement (LSM) using TE. Liver biopsies were evaluated for fibrosis, qualitatively, by Ishak score and quantitatively by fibrosis area fraction (FAF) using digital image analysis (morphometry). LSM was correlated with fibrosis and other studied variables using spearman correlation. A stepwise multiple regression analysis was also performed to examine independent factors associated with LSM. Different cut-off values of LSM were calculated for predicting individual fibrosis stages using receiver-operating characteristic curve. Cut-off values with optimal clinical performance (optimal sensitivity and specificity simultaneously) were selected. RESULTS: The majority of HCV group had minimal activity (80%) and no/mild fibrosis (72%). On the other hand, the majority of AIH group had mild to moderate activity (70%) and moderate to severe fibrosis (95%) and all Wilson disease group had mild to moderate activity (100%) and moderate to severe fibrosis (100%). LSM correlated significantly with both FAF and Ishak scores and the correlation appeared better with the latter (r = 0.839 vs 0.879, P < 0.0001 for both). LSM discriminated individual stages of fibrosis with high performance. Sensitivity ranged from 81.4% to 100% and specificity ranged from 75.0% to 97.2%. When we compared LSM values for the same stage of fibrosis, they varied according to the different etiologies. Higher values were in AIH (16.15 ± 7.23 kPa) compared to Wilson disease (8.30 ± 0.84 kPa) and HCV groups (7.43 ± 1.73 kPa). Multiple regression analysis revealed that Ishak fibrosis stage was the only independent variable

Methods to determine intestinal permeability and bacterial translocation during liver disease

PubMed Central

Wang, Lirui; Llorente, Cristina; Hartmann, Phillipp; Yang, An-Ming; Chen, Peng; Schnabl, Bernd

2015-01-01

Liver disease is often times associated with increased intestinal permeability. A disruption of the gut barrier allows microbial products and viable bacteria to translocate from the intestinal lumen to extraintestinal organs. The majority of the venous blood from the intestinal tract is drained into the portal circulation, which is part of the dual hepatic blood supply. The liver is therefore the first organ in the body to encounter not only absorbed nutrients, but also gut-derived bacteria and pathogen associated molecular patterns (PAMPs). Chronic exposure to increased levels of PAMPs has been linked to disease progression during early stages and to infectious complications during late stages of liver disease (cirrhosis). It is therefore important to assess and monitor gut barrier dysfunction during hepatic disease. We review methods to assess intestinal barrier disruption and discuss advantages and disadvantages. We will in particular focus on methods that we have used to measure increased intestinal permeability and bacterial translocation during experimental liver disease models. PMID:25595554

[Comparison of various noninvasive serum markers of liver fibrosis in chronic viral liver disease].

PubMed

Kim, Sun Min; Sohn, Joo Hyun; Kim, Tae Yeob; Roh, Young Wook; Eun, Chang Soo; Jeon, Yong Cheol; Han, Dong Soo; Oh, Young Ha

2009-12-01

The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (> or =F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (> or =F3). All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis.

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non-alcoholic fatty liver disease.

PubMed

Kato, Ken-Ichiro; Takeshita, Yumie; Misu, Hirofumi; Zen, Yoh; Kaneko, Shuichi; Takamura, Toshinari

2015-03-01

To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease. Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method. The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = -0.45, P < 0.001; grade r = -0.54, P < 0.001; stage r = -0.37, P < 0.01), but not with hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = -0.22, P < 0.05) and grade (coefficient = -0.40, P < 0.01) were associated with Matsuda index, whereas the association between stage and Matsuda index (coefficient = -0.07, P = 0.593) was no longer significant. A similar trend was observed for the association between steatosis and metabolic clearance rate (coefficient = -0.62, P = 0.059). Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.

Alcoholic liver disease.

PubMed

Penny, Steven M

2013-01-01

In the United States, approximately 100,000 deaths are attributed to alcohol abuse each year. In 2009, the World Health Organization listed alcohol use as one of the leading causes of the global burden of disease and injury. Alcoholic liver disease, a direct result of chronic alcohol abuse, insidiously destroys the normal functions of the liver. The end result of the disease, cirrhosis, culminates in a dysfunctional and diffusely scarred liver. This article discusses the clinical manifestations, imaging considerations, and treatment of alcoholic liver disease and cirrhosis. Normal liver function, liver hemodynamics, the disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

FIB-4 stage of liver fibrosis predicts incident heart failure among HIV-infected and uninfected patients.

PubMed

So-Armah, Kaku A; Lim, Joseph K; Lo Re, Vincent; Tate, Janet P; Chang, Chung-Chou H; Butt, Adeel A; Gibert, Cynthia L; Rimland, David; Marconi, Vincent C; Goetz, Matthew B; Rodriguez-Barradas, Maria C; Budoff, Matthew J; Tindle, Hilary A; Samet, Jeffrey H; Justice, Amy C; Freiberg, Matthew S

2017-10-01

Liver fibrosis is common, particularly in individuals who are infected with human immunodeficiency virus (HIV). HIV-infected individuals have excess congestive heart failure (CHF) risk compared with uninfected people. It remains unknown whether liver fibrosis stage influences the CHF risk or if HIV or hepatitis C virus (HCV) infection modifies this association. Our objectives were to assess whether 1) stage of liver fibrosis is independently associated with incident CHF and 2) the association between stage of liver fibrosis and incident CHF is modified by HIV/HCV status. Participants alive on or after April 1, 2003, in the Veterans Aging Cohort Study were included. Those without prevalent cardiovascular disease were followed until their first CHF event, death, last follow-up date, or December 31, 2011. Liver fibrosis was measured using the fibrosis 4 index (FIB-4), which is calculated using age, aminotransferases, and platelets. Cox proportional hazards regression models were adjusted for cardiovascular disease risk factors. Among 96,373 participants over 6.9 years, 3844 incident CHF events occurred. FIB-4 between 1.45 and 3.25 (moderate fibrosis) and FIB-4 > 3.25 (advanced fibrosis/cirrhosis) were associated with CHF (hazard ratio [95% confidence interval], 1.17 [1.07-1.27] and 1.65 [1.43-1.92], respectively). The association of advanced fibrosis/cirrhosis and incident CHF persisted regardless of HIV/HCV status. Moderate and advanced liver fibrosis/cirrhosis are associated with an increased risk of CHF. The association for advanced fibrosis/cirrhosis persists even among participants without hepatitis C and/or HIV infection. Assessing liver health may be important for reducing the risk of future CHF events, particularly among HIV and hepatitis C infected people among whom cardiovascular disease risk is elevated and liver disease is common. (Hepatology 2017;66:1286-1295). © 2017 by the American Association for the Study of Liver Diseases.

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

Liver disease - resources

MedlinePlus

Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services (C.L.A.S.S.) -- www. ...

Novel Potent Metallocenes against Liver Stage Malaria

PubMed Central

Matos, Joana; da Cruz, Filipa P.; Cabrita, Élia; Gut, Jiri; Nogueira, Fátima; do Rosário, Virgílio E.; Moreira, Rui; Rosenthal, Philip J.; Prudêncio, Miguel

2012-01-01

Novel conjugates of the antimalarial drug primaquine (compound 1) with ferrocene, named primacenes, have been synthesized and screened for their activities against blood stage and liver stage malaria in vitro and host-vector transmission in vivo. Both transmission-blocking and blood-schizontocidal activities of the parent drug were conserved only in primacenes bearing a basic aliphatic amine group. Liver stage activity did not require this structural feature, and all metallocenes tested were comparable to or better than primaquine in this regard. Remarkably, the replacement of primaquine's aliphatic chain by hexylferrocene, as in compound 7, led to a ∼45-fold-higher level activity against liver stage parasitemia than that of primaquine. PMID:22155838

Fatty Liver Disease

MedlinePlus

... fatty liver disease that is not related to heavy alcohol use. There are two kinds: Simple fatty ... disease? Alcoholic fatty liver disease is due to heavy alcohol use. Your liver breaks down most of ...

Impact of split completeness on future liver remnant hypertrophy in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in hepatocellular carcinoma: Complete-ALPPS versus partial-ALPPS.

PubMed

Chan, Albert C Y; Chok, Kenneth; Dai, Jeff W C; Lo, Chung Mau

2017-02-01

Recent evidence suggested that associating liver partition and portal vein ligation for staged hepatectomy with a partial split could effectively induce the same degree of future liver remnant hypertrophy as a complete split in non-cirrhotic and non-cholestatic livers with better postoperative safety profiles. Our aim was to evaluate if the same phenomenon could be applied to hepatitis-related chronic liver diseases. In the study, 25 patients who underwent associating liver partition and portal vein ligation for staged hepatectomy from October 2013 to January 2016 for hepatocellular carcinoma were analyzed. Partial-associating liver partition and portal vein ligation for staged hepatectomy (n = 12) was defined as 50-80% of the transection surface split and complete-associating liver partition and portal vein ligation for staged hepatectomy (n = 13) was split down to inferior vena cava. Perioperative outcomes stratified by split completeness were evaluated. There was no significant difference in operating times and blood loss for stage I and II operations between complete-associating liver partition and portal vein ligation for staged hepatectomy and partial-associating liver partition and portal vein ligation for staged hepatectomy. All patients underwent stage II operation without any inter-stage complications. Complete split induced greater future liver remnant hypertrophy than partial split (hypertrophy rate: 31.2 vs 17.5 mL/day, P = .022) with more pronounced effect in chronic hepatitis (P = .007) than cirrhosis (P = .283). Complete-associating liver partition and portal vein ligation for staged hepatectomy was more likely to attain a future liver remnant/estimated standard liver volume ratio >35% within 10 days (76.9% vs 33.3%, P = .024) and proceed to stage II within 14 days after stage I (100% vs 58.4%, P = .009). The overall postoperative morbidity (≥grade 3a) after stage II was 16% (complete versus partial split: 7.7% vs 25%, P = .238

Periodontal disease and liver cirrhosis: A systematic review

PubMed Central

2015-01-01

Objectives: Studies suggest that periodontal disease, a source of subclinical and persistent infection, may be associated with various systemic conditions, including liver cirrhosis. The aim of this study was to examine the literature and determine the relationship between periodontal disease and liver cirrhosis and to identify opportunities and directions for future research in this area. Methods: A systematic review of English articles in the PubMed, EMBASE, and Scopus databases was conducted using search terms including ‘liver cirrhosis’, ‘end-stage liver disease’, ‘liver diseases’, ‘oral health’, ‘periodontal disease’, ‘mouth disease’, ‘gingivitis’, and ‘periodontitis’. Results: Thirteen studies published between 1981 and 2014 were found to include data on oral health and periodontal disease in cirrhotic patients. Studies indicated an increased incidence of periodontal disease in patients with liver cirrhosis, measured with several different periodontal indices. The reported prevalence of periodontal disease in cirrhosis patients ranged from 25.0% to 68.75% in four studies and apical periodontitis was found in 49%–79% of the patients. One study found that mortality was lower among patients who underwent dental treatment versus non-treated patients. Another study suggested an association between periodontal disease and the progression of liver cirrhosis, but data are sparse and conflicting as to whether periodontal disease is correlated to cirrhosis aetiology and severity. Conclusion: Despite the clinical reality of periodontal disease in liver cirrhosis patients, there are few published studies. Before clinical implications can be addressed, more data on the prevalence of and correlation between periodontal disease and liver cirrhosis aetiology, duration, and progression are needed. PMID:26770799

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).

Factors influencing health-related quality of life in chronic liver disease

PubMed Central

Sobhonslidsuk, Abhasnee; Silpakit, Chatchawan; Kongsakon, Ronnachai; Satitpornkul, Patchareeya; Sripetch, Chaleaw; Khanthavit, Anya

2006-01-01

AIM: To investigate the factors contributing to health-related quality of life (HRQL) in chronic liver disease (CLD). METHODS: Patients with CLD and age- and sex-matched normal subjects performed the validated Thai versions of the short-form 36 (SF-36) by health survey and chronic liver disease questionnaire (CLDQ). Stepwise multiple regression analysis was used to assess the impact of disease severity, demography, causes of CLD, socioeconomic factors, and self-rating health perception on HRQL. RESULTS: Two-hundred and fifty patients with CLD and fifty normal subjects were enrolled into the study. Mean age and the numbers of low educated, unemployed, blue-collar career and poor health perception increased significantly from chronic hepatitis to Child’s Classes A to B to C. Advanced stage of CLD was related to deterioration of HRQL. Increasing age and female reduced physical health area. Low socioeconomic factors and financial burden affected multiple areas of HRQL. In overall, the positive impact of self-rating health perception on HRQL was consistently showed. CONCLUSION: Advanced stages of chronic liver disease, old age, female sex, low socioeconomic status and financial burden are important factors reducing HRQL. Good health perception improves HRQL regardless of stages of liver disease. PMID:17203521

Donation after cardiac death liver transplantation is associated with increased risk of end-stage renal disease.

PubMed

Ruebner, Rebecca L; Reese, Peter P; Abt, Peter L

2014-12-01

Limited organ supply has led to greater use of liver allografts with higher donor risk indices (DRI) and/or donated after cardiac death (DCD). DCD status is associated with acute kidney injury after liver transplantation; however, less is known about the association between donor quality and end-stage renal disease (ESRD). Using SRTR data, we assembled a cohort of liver transplant recipients from 2/2002 to 12/2010. We fit multivariable Cox regression models for ESRD. Model 1 included total DRI; model 2 included components of DRI, including DCD, as separate variables. Forty thousand four hundred and sixty-three liver transplant recipients were included. Median DRI was 1.40 (IQR 1.14, 1.72); 1822 (5%) received DCD livers. During median follow-up of 3.93 years, ESRD occurred in 2008 (5%) and death in 11 075 (27%) subjects. There was a stepwise increase in ESRD risk with higher DRI (DRI ≥1.14 and <1.40: HR 1.17, P = 0.06; DRI ≥1.40 and <1.72: HR 1.29, P = 0.003; DRI ≥1.72: HR 1.39, P < 0.001, compared with DRI <1.14). Adjusting for DRI components separately, DCD status was most strongly associated with ESRD (HR 1.40, P = 0.008). Higher DRI is associated with ESRD after liver transplantation, driven in part by DCD status. Donor quality is an important predictor of long-term renal outcomes in liver transplant recipients. © 2014 Steunstichting ESOT.

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 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

The postoperative Model for End stage Liver Disease score as a predictor of short-term outcome after transplantation of extended criteria donor livers.

PubMed

Benko, Tamas; Gallinat, Anja; Minor, Thomas; Saner, Fuat H; Sotiropoulos, Georgios C; Paul, Andreas; Hoyer, Dieter P

2017-06-01

Recently, the postoperative Model for End stage Liver Disease score (POPMELD) was suggested as a definition of postoperative graft dysfunction and a predictor of outcome after liver transplantation (LT). The aim of the present study was to validate this concept in the context of extended criteria donor (ECD) organs. Single-center prospectively collected data (OPAL study/01/11-12/13) of 116 ECD LTs were utilized. For each recipient, the Model for End stage Liver Disease (MELD) score was calculated for 7 postoperative days (PODs). The ability of international normalized ratio, bilirubin, aspartate aminotransferase, Donor Risk Index, a recent definition of early allograft dysfunction, and the POPMELD was compared to predict 90-day graft loss. Predictive abilities were compared by receiver operating characteristic curves, sensitivity and specificity, and positive and negative predictive values. The median Donor Risk Index was 1.8. In all, 60.3% of recipients were men [median age of 54 (23-68) years]. The median POD1-7 peak-aspartate aminotransferase value was 1052 (194-17 577) U/l. The rate of early allograft dysfunction was 22.4%. The 90-day graft survival was 89.7%. Out of possible predictors of the 90-day graft loss MELD on POD5 was the best predictor of outcome (area under the curve=0.84). A MELD score of 16 or more on POD5 predicted the 90-day graft loss with a specificity of 80.8%, a sensitivity of 81.8%, and a positive and negative predictive value of 31 and 97.7%. A MELD score of 16 or more on POD5 is an excellent predictor of outcome in ECD donor LT. Routine evaluation of POPMELD scores might support clinical decision-making and should be reported routinely in clinical trials.

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

PubMed

Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

2016-09-01

Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease.

PubMed

Schwimmer, Jeffrey B; Middleton, Michael S; Behling, Cynthia; Newton, Kimberly P; Awai, Hannah I; Paiz, Melissa N; Lam, Jessica; Hooker, Jonathan C; Hamilton, Gavin; Fontanesi, John; Sirlin, Claude B

2015-06-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI-estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. Liver PDFF estimated by MRI was significantly (P < 0.01) correlated (0.725) with steatosis grade. The correlation of MRI-estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (P < 0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly (P < 0.01) weaker in children with stage 2-4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI-estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. Advanced magnitude-based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus, magnitude-based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child. © 2015 by the American Association for the Study of Liver Diseases.

Liver Diseases

MedlinePlus

Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...

[Non-alcoholic fatty liver disease--new view].

PubMed

Raszeja-Wyszomirska, Joanna; Lawniczak, Małgorzata; Marlicz, Wojciech; Miezyńska-Kurtycz, Joanna; Milkiewicz, Piotr

2008-06-01

Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology--from steatosis alone, through the necroinflammatory disorder of non-alcoholic steatohepatitis (NASH) to cirrhosis and liver cancer. NAFLD/NASH is mostly related with visceral adiposity, obesity, type 2 diabetes melitus (DM t.2) and metabolic syndrome. Pathogenetic concepts of NAFLD include overnutrition and underactivity, insulin resistance (IR) and genetic factor. The prevalence of NAFLD has been estimated to be 17-33% in some countries, NASH may be present in about 1/3 of such cases, while 20-25% of NASH cases could progress to cirrhosis. NAFLD is now recognized as one of the most frequent reason of liver tests elevation without clinical symptoms. Insulin resistance is considering as having a central role in NAFLD pathogenesis. In hepatocytes, IR is related to hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly. Among clinical symptoms, abdominal discomfort is relatively common as well as chronic fatigue. NAFLD/NASH is not a benign disease, progressive liver biopsy have shown histological progression of fibrosis in 32%, the estimated rate of cirrhosis development is 20% and a liver--related death is 12% over 10 years. No treatment has scientifically proved to ameliorate NAFLD or to avoid its progression. The various therapeutic alternatives are aimed at interfering with the risk factors involved in the pathogenesis of the disorder in order to prevent the progression to end-stage liver disease. The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others

Alcoholic Liver Disease and Liver Transplantation.

PubMed

Gallegos-Orozco, Juan F; Charlton, Michael R

2016-08-01

Excessive alcohol use is a common health care problem worldwide and is associated with significant morbidity and mortality. Alcoholic liver disease represents the second most frequent indication for liver transplantation in North America and Europe. The pretransplant evaluation of patients with alcoholic liver disease should aim at identifying those at high risk for posttransplant relapse of alcohol use disorder, as return to excessive drinking can be deleterious to graft and patient survival. Carefully selected patients with alcoholic liver disease, including those with severe alcoholic hepatitis, will have similar short-term and long-term outcomes when compared with other indications for liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Physicians’ practices for diagnosing liver fibrosis in chronic liver diseases: A nationwide, Canadian survey

PubMed Central

Sebastiani, Giada; Ghali, Peter; Wong, Philip; Klein, Marina B; Deschenes, Marc; Myers, Robert P

2014-01-01

OBJECTIVE: To determine practices among physicians in Canada for the assessment of liver fibrosis in patients with chronic liver diseases. METHODS: Hepatologists, gastroenterologists, infectious diseases specialists, members of the Canadian Gastroenterology Association and/or the Canadian HIV Trials Network who manage patients with liver diseases were invited to participate in a web-based, national survey. RESULTS: Of the 237 physicians invited, 104 (43.9%) completed the survey. Routine assessment of liver fibrosis was requested by the surveyed physicians mostly for chronic hepatitis C (76.5%), followed by autoimmune/cholestatic liver disease (59.6%) and chronic hepatitis B (52.9%). Liver biopsy was the main diagnostic tool for 46.2% of the respondents, Fibroscan (Echosens, France) for 39.4% and Fibrotest (LabCorp, USA) for 7.7%. Etiology-specific differences were observed: noninvasive methods were mostly used for hepatitis C (63% versus 37% liver biopsy) and hepatitis B (62.9% versus 37.1% liver biopsy). For 42.7% of respondents, the use of noninvasive methods reduced the need for liver biopsy by >50%. Physicians’ characteristics associated with higher use of noninvasive methods were older age and being based at a university hospital or in private practice versus community hospital. Physicians’ main concerns regarding noninvasive fibrosis assessment methods were access/availability (42.3%), lack of guidelines for clinical use (26.9%) and cost/lack of reimbursement (14.4%). CONCLUSIONS: Physicians who manage patients with chronic liver diseases in Canada require routine assessment of liver fibrosis stage. Although biopsy remains the primary diagnostic tool for almost one-half of respondents, noninvasive methods, particularly Fibroscan, have significantly reduced the need for liver biopsy in Canada. Limitations in access to and availability of the noninvasive methods represent a significant barrier. Finally, there is a need for clinical guidelines and a better

ARFI cut-off values and significance of standard deviation for liver fibrosis staging in patients with chronic liver disease.

PubMed

Goertz, Ruediger S; Sturm, Joerg; Pfeifer, Lukas; Wildner, Dane; Wachter, David L; Neurath, Markus F; Strobel, Deike

2013-01-01

Acoustic radiation force impulse (ARFI) elastometry quantifies hepatic stiffness, and thus degree of fibrosis, non-invasively. Our aim was to analyse the diagnostic accuracy of ARFI cut-off values, and the significance of a defined limit of standard deviation (SD) as a potential quality parameter for liver fibrosis staging in patients with chronic liver diseases (CLD). 153 patients with CLD (various aetiologies) undergoing liver biopsy, and an additional 25 patients with known liver cirrhosis, were investigated. ARFI measurements were performed in the right hepatic lobe, and correlated with the histopathological Ludwig fibrosis score (inclusion criteria: at least 6 portal tracts). The diagnostic accuracy of cut-off values was analysed with respect to an SD limit of 30% of the mean ARFI value. The mean ARFI elastometry showed 1.95 ± 0.87 m/s (range 0.79-4.40) in 178 patients (80 female, 98 male, mean age: 52 years). The cut-offs were 1.25 m/s for F ≥ 2, 1.72 m/s for F ≥ 3 and 1.75 m/s for F = 4, and the corresponding AUROC 80.7%, 86.2% and 88.7%, respectively. Exclusion of 31 patients (17.4%) with an SD higher than 30% of the mean ARFI improved the diagnostic accuracy: The AUROC for F ≥ 2, F ≥ 3 and F = 4 were 86.1%, 91.2% and 91.5%, respectively. The diagnostic accuracy of ARFI can be improved by applying a maximum SD of 30% of the mean ARFI as a quality parameter--which however leads to an exclusion of a relevant number of patients. ARFI results with a high SD should be interpreted with caution.

Platelets: No longer bystanders in liver disease

PubMed Central

Adams, David H.; Watson, Steve P.; Lalor, Patricia F.

2016-01-01

Growing lines of evidence recognize that platelets play a central role in liver homeostasis and pathobiology. Platelets have important roles at every stage during the continuum of liver injury and healing. These cells contribute to the initiation of liver inflammation by promoting leukocyte recruitment through sinusoidal endothelium. They can activate effector cells, thus amplifying liver damage, and by modifying the hepatic cellular and cytokine milieu drive both hepatoprotective and hepatotoxic processes. Conclusion: In this review we summarize how platelets drive such pleiotropic actions and attempt to reconcile the paradox of platelets being both deleterious and beneficial to liver function; with increasingly novel methods of manipulating platelet function at our disposal, we highlight avenues for future therapeutic intervention in liver disease. (Hepatology 2016;64:1774‐1784) PMID:26934463

Background and design of the symptom burden in end-stage liver disease patient-caregiver dyad study.

PubMed

Hansen, Lissi; Lyons, Karen S; Dieckmann, Nathan F; Chang, Michael F; Hiatt, Shirin; Solanki, Emma; Lee, Christopher S

2017-10-01

Over half a million Americans are affected by cirrhosis, the cause of end-stage liver disease (ESLD). Little is known about how symptom burden changes over time in adults with ESLD and their informal caregivers, which limits our ability to develop palliative care interventions that can optimize symptom management and quality of life in different patient-caregiver dyads. The purpose of this article is to describe the background and design of a prospective, longitudinal descriptive study, "Symptom Burden in End-Stage Liver Disease Patient-Caregiver Dyads," which is currently in progress. The study is designed to (i) identify trajectories of change in physical and psychological symptom burden in adults with ESLD; (ii) identify trajectories of change in physical and psychological symptom burden in caregivers of adults with ESLD; and (iii) determine predictors of types of patient-caregiver dyads that would benefit from tailored palliative care interventions. We aim for a final sample of 200 patients and 200 caregivers who will be followed over 12 months. Integrated multilevel and latent growth mixture modeling will be used to identify trajectories of change in symptom burden, linking those changes to clinical events, and quality of life outcomes and characterizing types of patient-caregiver dyads based on patient-, caregiver-, and dyad-level factors. Challenges we have encountered include unexpected attrition of study participants, participants not returning their baseline questionnaires, and hiring and training of research staff. The study will lay the foundation for future research and innovation in ESLD, end-of-life and palliative care, and caregiving. © 2017 Wiley Periodicals, Inc.

Increased Level of Interleukin 6 Associates With Increased 90-Day and 1-Year Mortality in Patients With End-Stage Liver Disease.

PubMed

Remmler, Johannes; Schneider, Christoph; Treuner-Kaueroff, Theresa; Bartels, Michael; Seehofer, Daniel; Scholz, Markus; Berg, Thomas; Kaiser, Thorsten

2018-05-01

Organ allocation for liver transplantation is based on prognosis, using the model for end-stage liver disease (MELD) or MELD including serum sodium (MELD-Na) score. These scores do not consider systemic inflammation and septic complications. Blood level of C-reactive protein (CRP), in addition to the MELD score, associates with mortality in patients with end-stage liver disease, whereas levels of interleukin 6 (IL6) have not been systematically studied. We performed a retrospective observational cohort study of 474 patients with end-stage liver disease (63.5% male; median age, 56.9 years), evaluated for liver transplantation in Germany, with at least 1 year of follow up. Data were collected on blood levels of CRP, IL6, and white blood cell count (WBC). Findings were analyzed in relation to mortality and compared with patients' MELD scores and MELD-Na scores. For survival analysis, the cohort was divided into quartiles of IL6, CRP, and WBC levels, as well as MELD scores. Log-rank test and the Cox proportional hazards regression model were used to compare the groups, and area under the receiver operating characteristic (AUROC) values were calculated. Blood levels of IL6 and MELD scores associated with mortality: none of the patients with levels of IL6 below the first quartile (below 5.3 pg/mL) died within 1 year. In contrast, 67.7% of the patients in the highest quartile of IL6 level (37.0 pg/mL or more) died within 1 year. MELD score also correlated with mortality: among patients with MELD scores below 8.7, 0.9% died within 1 year, whereas in patients with MELD scores of 18.0 or more, 67.4% died within 1 year. The predictive value of level of IL6 (AUROC, 0.940) was higher than level of CRP (AUROC, 0.866) (P = .009) or WBC (AUROC, 0.773) (P < .001) for 90-day mortality. MELD scores associated with 90-day mortality (AUROC, 0.933) (P = .756) as did MELD-Na score (AUROC, 0.946) (P = .771). Level of IL6 associated with 1-year mortality (AUROC, 0.916) to a greater

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

Progression of Liver Disease

MedlinePlus

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Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease.

PubMed

Santetti, Daniele; de Albuquerque Wilasco, Maria Inês; Dornelles, Cristina Toscani Leal; Werlang, Isabel Cristina Ribas; Fontella, Fernanda Urruth; Kieling, Carlos Oscar; Dos Santos, Jorge Luiz; Vieira, Sandra Maria Gonçalves; Goldani, Helena Ayako Sueno

2015-08-07

To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease. We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease (MELD) and Pediatric End Stage Liver Disease (PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition (Z-score < -1.00) and malnutrition (Z-score < -2.00). Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. The median (25(th)-75(th) centile) age of the study population was 60 (17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease (72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values ​​were increased in patients at nutritional risk (34.9%) compared with those who were well-nourished [7.12 (0.58-34.23) pg/mL vs 1.63 (0.53-3.43) pg/mL; P = 0.02], correlating inversely with triceps skinfold-for-age z-score (rs = -0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score (P = 0

Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease

PubMed Central

Santetti, Daniele; de Albuquerque Wilasco, Maria Inês; Dornelles, Cristina Toscani Leal; Werlang, Isabel Cristina Ribas; Fontella, Fernanda Urruth; Kieling, Carlos Oscar; dos Santos, Jorge Luiz; Vieira, Sandra Maria Gonçalves; Goldani, Helena Ayako Sueno

2015-01-01

AIM: To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease. METHODS: We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease (MELD) and Pediatric End Stage Liver Disease (PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition (Z-score < -1.00) and malnutrition (Z-score < -2.00). Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. RESULTS: The median (25th-75th centile) age of the study population was 60 (17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease (72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values ​​were increased in patients at nutritional risk (34.9%) compared with those who were well-nourished [7.12 (0.58-34.23) pg/mL vs 1.63 (0.53-3.43) pg/mL; P = 0.02], correlating inversely with triceps skinfold-for-age z-score (rs = -0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child

Assessment of Liver Viscoelasticity for the Diagnosis of Early Stage Fatty Liver Disease Using Transient Elastography

NASA Astrophysics Data System (ADS)

Remenieras, Jean-Pierre; Dejobert, Maelle; Bastard, Cécile; Miette, Véronique; Perarnau, Jean-Marc; Patat, Frédéric

Nonalcoholic fatty liver disease (NAFLD) is characterized by accumulation of fat within the Liver. The main objective of this work is (1) to evaluate the feasibility of measuring in vivo in the liver the shear wave phase velocity dispersion cs(ω) between 20 Hz and 90 Hz using vibration-controlled transient elastography (VCTE); (2) to estimate through the rheological Kelvin-Voigt model the shear elastic μ and shear viscosity η modulus; (3) to correlate the evolution of these viscoelastic parameters on two patients at Tours Hospital with the hepatic fat percentage measured with T1-weighted gradient-echo in-and out-phase MRI sequence. For the first volunteer who has 2% of fat in the liver, we obtained μ = 1233 ± 133 Pa and η = 0.5 ± 0.4 Pa.s. For the patient with 22% of fat, we measure μ = 964 ± 91 Pa and η = 1.77 ± 0.3 Pa.s. In conclusion, this novel method showed to be sensitive in characterizing the visco-elastic properties of fatty liver.

Shear-Wave Elastography for the Estimation of Liver Fibrosis in Chronic Liver Disease: Determining Accuracy and Ideal Site for Measurement

PubMed Central

Dhyani, Manish; Vij, Abhinav; Bhan, Atul K.; Halpern, Elkan F.; Méndez-Navarro, Jorge; Corey, Kathleen E.; Chung, Raymond T.

2015-01-01

Purpose To evaluate the accuracy of shear-wave elastography (SWE) for staging liver fibrosis in patients with diffuse liver disease (including patients with hepatitis C virus [HCV]) and to determine the relative accuracy of SWE measurements obtained from different hepatic acquisition sites for staging liver fibrosis. Materials and Methods The institutional review board approved this single-institution prospective study, which was performed between January 2010 and March 2013 in 136 consecutive patients who underwent SWE before their scheduled liver biopsy (age range, 18–76 years; mean age, 49 years; 70 men, 66 women). Informed consent was obtained from all patients. SWE measurements were obtained at four sites in the liver. Biopsy specimens were reviewed in a blinded manner by a pathologist using METAVIR criteria. SWE measurements and biopsy results were compared by using the Spearman correlation and receiver operating characteristic (ROC) curve analysis. Results SWE values obtained at the upper right lobe showed the highest correlation with estimation of fibrosis (r = 0.41, P < .001). Inflammation and steatosis did not show any correlation with SWE values except for values from the left lobe, which showed correlation with steatosis (r = 0.24, P = .004). The area under the ROC curve (AUC) in the differentiation of stage F2 fibrosis or greater, stage F3 fibrosis or greater, and stage F4 fibrosis was 0.77 (95% confidence interval [CI]: 0.68, 0.86), 0.82 (95% CI: 0.75, 0.91), and 0.82 (95% CI: 0.70, 0.95), respectively, for all subjects who underwent liver biopsy. The corresponding AUCs for the subset of patients with HCV were 0.80 (95% CI: 0.67, 0.92), 0.82 (95% CI: 0.70, 0.95), and 0.89 (95% CI: 0.73, 1.00). The adjusted AUCs for differentiating stage F2 or greater fibrosis in patients with chronic liver disease and those with HCV were 0.84 and 0.87, respectively. Conclusion SWE estimates of liver stiffness obtained from the right upper lobe showed the best

Gut microbiota and liver diseases

PubMed Central

Minemura, Masami; Shimizu, Yukihiro

2015-01-01

Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

Phase angle as a nutritional evaluation tool in all stages of chronic liver disease.

PubMed

Peres, W A F; Lento, D F; Baluz, K; Ramalho, A

2012-01-01

Malnutrition is commonly and frequently under-diagnosed in clinical settings in patients with chronic liver disease (CLD) due to the limitations of nutritional evaluation methods in this population. We hypothesized that the bioelectrical impedance analysis derived phase angle (BIA-derived PhA) might be considered as a nutritional indicator in CLD since it represents either cell death or malnutrition characterized by changes in cellular membrane integrity. The aim of this study was to evaluate the BIA-derived PhA as a nutritional evaluation tool in all stages of CLD, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). Liver-related death and survival were evaluated. A total of 66 patients were enrolled in a cross-sectional study. For the nutritional diagnosis, mid-arm circumference (MAC), triceps skinfold thickness (TST), mid-arm muscle circumference (MAMC) and Subject Global Assessment (SGA) were evaluated. Biochemical and clinical evaluations were performed. Our results showed that PhA was higher in well-nourished patients, according to SGA and in the patients without hepatic encephalopathy. PhA correlated significantly with MAMC, MAC and albumin and was inversely correlated with age. No correlation was found between PhA values and the Child-Pugh score and ascites. PhA was strongly associated with survival and PhA ≤ 5.18º with relative risk increase of 2.5 for death. We conclude that the BIA-derived PhA is a relevant nutritional evaluation tool in chronic hepatitis, liver cirrhosis and HCC and the role of PhA in the prediction of survival in CLD should be examined further in a controlled study.

Association of Pretransplantion Opioid Use with Graft Loss or Death in Liver Transplantation Patients with Model of End-Stage Liver Disease Exceptions.

PubMed

Fleming, James N; Taber, David J; Pilch, Nicole A; Mardis, Caitlin R; Gilbert, Rachael E; Wilson, Lytani Z; Patel, Neha; Ball, Sarah; Mauldin, Patrick; Baliga, Prabhakar K

2018-04-01

Up to 77% of liver transplantation candidates experience pain, and the majority are prescribed opioids. Previous studies have shown increased readmissions and mortality in liver transplant recipients who were prescribed opioids before transplantation. Our aim was to identify specific populations that are at the highest risk for deleterious outcomes with opioid use before transplantation. This was a single-center retrospective cohort study of adult receiving liver transplants between 2010 and 2016 to assess the impact of pretransplantation opioid use on mortality and graft loss after liver transplantation. A total of 446 liver transplant recipients were included in the study, 148 (33%) of which were identified as pretransplantation opioid users. Opioid use increased significantly during the course of the study. There were no differences in the overall cohort between opioid users and non-opioid users with regard to graft or patient outcomes. However, the influence of opioid use on outcomes varied based on Model for End-Stage Liver Disease (MELD) and functional status. In patients with any MELD exception, opioid use was an independent predictor of time to graft loss or death (adjusted hazard ratio 2.36; 95% CI 1.05 to 5.28; p = 0.037). It also independently predicted time to graft loss or death in patients with low laboratory MELD scores (adjusted hazard ratio 2.38; 95% CI 1.10 to 5.13; p = 0.027). In our 6-year retrospective cohort, pretransplantation opioid use based on medication reconciliation was independently associated with time to graft loss or mortality in liver transplant recipients with MELD exceptions and laboratory MELD scores ≤15. Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Study of FibroTest and hyaluronic acid biological variation in healthy volunteers and comparison of serum hyaluronic acid biological variation between chronic liver diseases of different etiology and fibrotic stage using confidence intervals.

PubMed

Istaces, Nicolas; Gulbis, Béatrice

2015-07-01

Personalized ranges of liver fibrosis serum biomarkers such as FibroTest or hyaluronic acid could be used for early detection of fibrotic changes in patients with progressive chronic liver disease. Our aim was to generate reliable biological variation estimates for these two biomarkers with confidence intervals for within-subject biological variation and reference change value. Nine fasting healthy volunteers and 66 chronic liver disease patients were included. Biological variation estimates were calculated for FibroTest in healthy volunteers, and for hyaluronic acid in healthy volunteers and chronic liver disease patients stratified by etiology and liver fibrosis stage. In healthy volunteers, within-subject biological coefficient of variation (with 95% confidence intervals) and index of individuality were 20% (16%-28%) and 0.6 for FibroTest and 34% (27%-47%) and 0.79 for hyaluronic acid, respectively. Overall hyaluronic acid within-subject biological coefficient of variation was similar among non-alcoholic fatty liver disease and chronic hepatitis C with 41% (34%-52%) and 45% (39%-55%), respectively, in contrast to chronic hepatitis B with 170% (140%-215%). Hyaluronic acid within-subject biological coefficients of variation were similar between F0-F1, F2 and F3 liver fibrosis stages in non-alcoholic fatty liver disease with 34% (25%-49%), 41% (31%-59%) and 34% (23%-62%), respectively, and in chronic hepatitis C with 34% (27%-47%), 33% (26%-45%) and 38% (27%-65%), respectively. However, corresponding hyaluronic acid indexes of individuality were lower in the higher fibrosis stages. Non-overlapping confidence intervals of biological variation estimates allowed us to detect significant differences regarding hyaluronic acid biological variation between chronic liver disease subgroups. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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.

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.

Human intrahepatic ILC2 are IL-13positive amphiregulinpositive and their frequency correlates with model of end stage liver disease score.

PubMed

Jeffery, Hannah C; McDowell, Patrick; Lutz, Philipp; Wawman, Rebecca E; Roberts, Sheree; Bagnall, Chris; Birtwistle, Jane; Adams, David H; Oo, Ye Htun

2017-01-01

Innate lymphoid cells (ILC) have been implicated in the initiation of inflammation and fibrosis in mice. However, ILC have not been characterized in inflamed human liver tissue. Human intrahepatic lymphocytes were isolated by mechanical digestion and phenotyped by flow cytometry. Conditioned medium from cultures of primary human biliary epithelial cells, stellate cells, fibroblasts and inflamed human liver tissue was used to model the effects of the inflammatory liver environment of ILC phenotype and function. All three ILC subsets were present in the human liver, with the ILC1 (CRTH2negCD117neg) subset constituting around 70% of intrahepatic ILCs. Both NCRpos (NKp44+) and NCRneg ILC3 (CRTH2negCD117pos) subsets were also detected. ILC2 (CRTH2pos) frequency correlated with disease severity measured by model of end stage liver disease (MELD) scoring leading us to study this subset in more detail. ILC2 displayed a tissue resident CD69+ CD161++ phenotype and expressed chemokine receptor CCR6 allowing them to respond to CCL20 secreted by cholangiocytes and stellate cells. ILC2 expressed integrins VLA-5 and VLA-6 and the IL-2 and IL-7 cytokine receptors CD25 and CD127 although IL-2 and IL-7 were barely detectable in inflamed liver tissue. Although biliary epithelial cells secrete IL-33, intrahepatic ILC2 had low expression of the ST2 receptor. Intrahepatic ILC2 secreted the immunoregulatory and repair cytokines IL-13 and amphiregulin. Intrahepatic ILC2 express receptors allowing them to be recruited to bile ducts in inflamed portal tracts. Their frequencies increased with worsening liver function. Their secretion of IL-13 and amphiregulin suggests they may be recruited to promote resolution and repair and thereby they may contribute to ongoing fibrogenesis in liver disease.

Epidemiology and mortality of liver abscess in end-stage renal disease dialysis patients: Taiwan national cohort study.

PubMed

Hong, Chon-Seng; Chung, Kun-Ming; Huang, Po-Chang; Wang, Jhi-Joung; Yang, Chun-Ming; Chu, Chin-Chen; Chio, Chung-Ching; Chang, Fu-Lin; Chien, Chih-Chiang

2014-01-01

To determine the incidence rates and mortality of liver abscess in ESRD patients on dialysis. Using Taiwan's National Health Insurance Research Database, we collected data from all ESRD patients who initiated dialysis between 2000 and 2006. Patients were followed until death, end of dialysis, or December 31, 2008. Predictors of liver abscess and mortality were identified using Cox models. Of the 53,249 incident dialysis patients identified, 447 were diagnosed as having liver abscesses during the follow-up period (224/100,000 person-years). The cumulative incidence rate of liver abscess was 0.3%, 1.1%, and 1.5% at 1 year, 5 years, and 7 years, respectively. Elderly patients and patients on peritoneal dialysis had higher incidence rates. The baseline comorbidities of diabetes mellitus, polycystic kidney disease, malignancy, chronic liver disease, biliary tract disease, or alcoholism predicted development of liver abscess. Overall in-hospital mortality was 10.1%. The incidence of liver abscess is high among ESRD dialysis patients. In addition to the well known risk factors of liver abscess, two other important risk factors, peritoneal dialysis and polycystic kidney disease, were found to predict liver abscess in ESRD dialysis patients.

Coffee and Liver Disease.

PubMed

Wadhawan, Manav; Anand, Anil C

2016-03-01

Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality.

Cannabis use is associated with reduced prevalence of progressive stages of alcoholic liver disease.

PubMed

Adejumo, Adeyinka C; Ajayi, Tokunbo O; Adegbala, Oluwole M; Adejumo, Kelechi L; Alliu, Samson; Akinjero, Akintunde M; Onyeakusi, Nnaemeka E; Ojelabi, Ogooluwa; Bukong, Terence N

2018-01-17

Abusive alcohol use has well-established health risks including causing liver disease (ALD) characterized by alcoholic steatosis (AS), steatohepatitis (AH), fibrosis, cirrhosis (AC) and hepatocellular carcinoma (HCC). Strikingly, a significant number of individuals who abuse alcohol also use Cannabis, which has seen increased legalization globally. While cannabis has demonstrated anti-inflammatory properties, its combined use with alcohol and the development of liver disease remain unclear. The aim of this study was to determine the effects of cannabis use on the incidence of liver disease in individuals who abuse alcohol. We analysed the 2014 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (NIS) discharge records of patients 18 years and older, who had a past or current history of abusive alcohol use (n = 319 514). Using the International Classification of Disease, Ninth Edition codes, we studied the four distinct phases of progressive ALD with respect to three cannabis exposure groups: non-cannabis users (90.39%), non-dependent cannabis users (8.26%) and dependent cannabis users (1.36%). We accounted for the complex survey sampling methodology and estimated the adjusted odds ratio (AOR) for developing AS, AH, AC and HCC with respect to cannabis use (SAS 9.4). Our study revealed that among alcohol users, individuals who additionally use cannabis (dependent and non-dependent cannabis use) showed significantly lower odds of developing AS, AH, AC and HCC (AOR: 0.55 [0.48-0.64], 0.57 [0.53-0.61], 0.45 [0.43-0.48] and 0.62 [0.51-0.76]). Furthermore, dependent users had significantly lower odds than non-dependent users for developing liver disease. Our findings suggest that cannabis use is associated with a reduced incidence of liver disease in alcoholics. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Performance-based measures associate with frailty in patients with end-stage liver disease

PubMed Central

Lai, Jennifer C.; Volk, Michael L; Strasburg, Debra; Alexander, Neil

2016-01-01

Background Physical frailty, as measured by the Fried Frailty Index, is increasingly recognized as a critical determinant of outcomes in cirrhotics. However, its utility is limited by the inclusion of self-reported components. We aimed to identify performance-based measures associated with frailty in patients with cirrhosis. Methods Cirrhotics ≥50 years underwent: 6-minute walk test (6MWT, cardiopulmonary endurance), chair stands in 30 seconds (muscle endurance), isometric knee extension (lower extremity strength), unipedal stance time (static balance), and maximal step length (dynamic balance/coordination). Linear regression associated each physical performance test with frailty. Principal components exploratory factor analysis evaluated the inter-relatedness of frailty and the 5 physical performance tests. Results Of forty cirrhotics, with a median age of 64 years and Model for End-stage Liver Disease (MELD) MELD of 12,10 (25%) were frail by Fried Frailty Index ≥3. Frail cirrhotics had poorer performance in 6MWT distance (231 vs. 338 meters), 30 second chair stands (7 vs. 10), isometric knee extension (86 vs. 122 Newton meters), and maximal step length (22 vs. 27 inches) [p≤0.02 for each]. Each physical performance test was significantly associated with frailty (p<0.01), even after adjustment for MELD or hepatic encephalopathy. Principal component factor analysis demonstrated substantial, but unique, clustering of each physical performance test to a single factor – frailty. Conclusion Frailty in cirrhosis is a multi-dimensional construct that is distinct from liver dysfunction and incorporates endurance, strength, and balance. Our data provide specific targets for prehabilitation interventions aimed at reducing frailty in cirrhotics in preparation for liver transplantation. PMID:27495749

Performance-Based Measures Associate With Frailty in Patients With End-Stage Liver Disease.

PubMed

Lai, Jennifer C; Volk, Michael L; Strasburg, Debra; Alexander, Neil

2016-12-01

Physical frailty, as measured by the Fried Frailty Index, is increasingly recognized as a critical determinant of outcomes in patients with cirrhosis. However, its utility is limited by the inclusion of self-reported components. We aimed to identify performance-based measures associated with frailty in patients with cirrhosis. Patients with cirrhosis, aged 50 years or older, underwent: 6-minute walk test (cardiopulmonary endurance), chair stands in 30 seconds (muscle endurance), isometric knee extension (lower extremity strength), unipedal stance time (static balance), and maximal step length (dynamic balance/coordination). Linear regression associated each physical performance test with frailty. Principal components exploratory factor analysis evaluated the interrelatedness of frailty and the 5 physical performance tests. Of 40 patients with cirrhosis, with a median age of 64 years and Model for End-stage Liver Disease (MELD) MELD of 12.10 (25%) were frail by Fried Frailty Index ≥3. Frail patients with cirrhosis had poorer performance in 6-minute walk test distance (231 vs 338 m), 30-second chair stands (7 vs 10), isometric knee extension (86 vs 122 Newton meters), and maximal step length (22 vs 27 in. (P ≤ 0.02 for each). Each physical performance test was significantly associated with frailty (P < 0.01), even after adjustment for MELD or hepatic encephalopathy. Principal component factor analysis demonstrated substantial, but unique, clustering of each physical performance test to a single factor-frailty. Frailty in cirrhosis is a multidimensional construct that is distinct from liver dysfunction and incorporates endurance, strength, and balance. Our data provide specific targets for prehabilitation interventions aimed at reducing frailty in patients with cirrhosis in preparation for liver transplantation.

Alcoholic liver disease: The gut microbiome and liver crosstalk

PubMed Central

Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

2015-01-01

Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier or preventing cellular responses to microbial products protect from experimental alcoholic liver disease. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of alcoholic liver disease. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship and consequences for alcoholic liver disease. We also discuss how the liver affects the intestinal microbiota. PMID:25872593

Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score.

PubMed

Kalafateli, Maria; Mantzoukis, Konstantinos; Choi Yau, Yan; Mohammad, Ali O; Arora, Simran; Rodrigues, Susana; de Vos, Marie; Papadimitriou, Kassiani; Thorburn, Douglas; O'Beirne, James; Patch, David; Pinzani, Massimo; Morgan, Marsha Y; Agarwal, Banwari; Yu, Dominic; Burroughs, Andrew K; Tsochatzis, Emmanuel A

2017-02-01

Although malnutrition and sarcopenia are prevalent in cirrhosis, their impact on outcomes following liver transplantation is not well documented. The associations of nutritional status and sarcopenia with post-transplant infections, requirement for mechanical ventilation, intensive care (ICU) and hospital stay, and 1 year mortality were assessed in 232 consecutive transplant recipients. Nutritional status and sarcopenia were assessed using the Royal Free Hospital-Global Assessment (RFH-GA) tool and the L3-psoas muscle index (L3-PMI) on CT, respectively. A wide range of RFH-SGA and L3-PMI were observed within similar Model for End-stage Liver Disease (MELD) sub-categories. Malnutrition and sarcopenia were independent predictors of all outcomes. Post-transplant infections were associated with MELD (OR = 1.055, 95%CI = 1.002-1.11) and severe malnutrition (OR = 6.55, 95%CI = 1.99-21.5); ventilation > 24 h with MELD (OR = 1.1, 95%CI = 1.036-1.168), severe malnutrition (OR = 8.5, 95%CI = 1.48-48.87) and suboptimal donor liver (OR = 2.326, 95%CI = 1.056-5.12); ICU stay > 5 days, with age (OR = 1.054, 95%CI = 1.004-1.106), MELD (OR = 1.137, 95%CI = 1.057-1.223) and severe malnutrition (OR = 7.46, 95%CI = 1.57-35.43); hospital stay > 20 days with male sex (OR = 2.107, 95%CI = 1.004-4.419) and L3-PMI (OR = 0.996, 95%CI = 0.994-0.999); 1 year mortality with L3-PMI (OR = 0.996, 95%CI = 0.992-0.999). Patients at the lowest L3-PMI receiving suboptimal grafts had longer ICU/hospital stay and higher incidence of infections. Malnutrition and sarcopenia are associated with early post-liver transplant morbidity/mortality. Allocation indices do not include nutritional status and may jeopardize outcomes in nutritionally compromised individuals.

Liver Disease in Sri Lanka.

PubMed

Wijewantha, Hasitha S

2017-01-01

Liver disease in Sri Lanka is mainly due to alcoholic liver disease and nonalcoholic fatty liver disease. In contrast to other South Asian countries, the prevalence of hepatitis B and C is low in Sri Lanka and prevalence of hepatitis A is intermediate. The few reported cases of hepatitis E in Sri Lanka are mainly in people who have traveled to neighboring South Asian countries. Wilson's disease, autoimmune hepatitis, hemochromatosis, drug-induced liver disease, and primary biliary cirrhosis are recognized causes of liver disease in Sri Lanka. Pyogenic and amebic liver abscesses and dengue infection are the other causes of liver disease. Some of the commonly used plants as traditional herbal medicine in Sri Lanka have been shown to have deleterious effects on the liver in animal studies. Considering the high popularity of traditional herbal medicine in the country, it is likely that herbal medicine is an etiological factor for liver disease in Sri Lanka, but no published data are available. Address reprint requests to: Wijewantha HS. Liver Disease in Sri Lanka. Euroasian J Hepato-Gastroenterol 2017;7(1):78-81.

Chronic Liver Diseases in Children: Clinical Profile and Histology.

PubMed

Dhole, Sachin Devidas; Kher, Archana S; Ghildiyal, Radha G; Tambse, Manjusha P

2015-07-01

The main aim of the study is to study the clinical profile of disorders of the liver and hepatobiliary system in paediatric patients and to correlate the histopathology findings of liver biopsy in chronic liver disease. Another aim being to assess the prognosis and to know the outcome and the effects of treatment in chronic liver diseases in paediatric age group. It was a prospective study, included the clinical profile of Chronic Liver Diseases (CLD) in children and the histopathological correlation. A total of 55 children were thoroughly investigated by doing relevant investigations and liver biopsy. A male predominance (60%) was noted with maximum incidence in the age group of 6-12 years. The incidence of CLD was 1.1% of total admissions. The most common presenting complaint was jaundice and abdominal distension. Hepatic encephalopathy was noted in 29% patients. Hepatomegaly was seen in 63% patients and spleenomegaly was seen in 60% patients. The incidence of cirrhosis on liver biopsy was 42% (23cases) in CLD patients. The most common diagnosis on histopathology was Wilson's disease (22%), followed by hepatitis and autoimmune hepatitis. The predominant spectrum of CLD was metabolic liver disease and also the predominant cause of death. As the incidence of CLD is quite low, a very high index of suspicion is required for its diagnosis. Some uncommon causes of CLD in children were seen in our study like neutral lipid storage disease, α1-Antitrypsin deficiency disease, lupus hepatitis, Alagille syndrome and Budd-Chiari syndrome. A patient of CLD with jaundice and hepatomegaly should be treated aggressively as those are the poor prognostic indicators of the disease. Hepatic encephalopathy and cirrhosis are also associated with poor outcome in patients with CLD. Liver biopsy histopathology by an expert and its correlation with laboratory investigations plays an important role in the diagnosis of CLD. The major cause of deaths in patients with CLD is due to end stage

Based on surface-enhanced Raman spectroscopy analysis of serum albumin in different stages of liver disease for early screening primary liver cancer

NASA Astrophysics Data System (ADS)

Liao, Fadian; Ruan, Qiuyong; Lin, Juqiang; Lin, Jinyong; Zeng, Yongyi; Li, Ling; Huang, Zufang; Liu, Nenrong; Chen, Rong

2014-09-01

Despite the introduction of high-technology methods of detection and diagnosis, screening of primary liver cancer (PLC) remains imperfect. To diagnosis PLC earlier, Surface-enhanced Raman spectroscopy (SERS) coupled with cellulose-acetate membrane electrophoresis were introduced to separate human serum albumin and SERS spectra. Three groups (15 normal persons' samples, 17 hepatitis/cirrhosis samples, 15 cases of PLC) of serum albumin were tested. Silver colloid was used to obtain SERS spectra of human serum albumin. Principal component analysis (PCA) and linear discriminant analysis (LDA) were also employed for statistical analysis. The mean Raman spectra of three groups and the difference spectra of any two suggested that the albumin has changed in liver patients. Compared to normal groups, some Raman peaks have shifted or even disappeared in hepatitis/cirrhosis and PLCs groups. The sensitivity and specificity between PLCs and normal groups is 80% and 93.3%. Among hepatitis/cirrhosis and normal groups, the sensitivity is 88.2% and specificity is also 93.3%. Besides, the sensitivity and specificity between PLCs and hepatitis/cirrhosis groups is 86.7% and 76.5%. All the above data and results indicated that early screening of PLC is potential by SERS in different stages of liver disease before cancer occurs.

Electrolyte and Acid-Base Disturbances in End-Stage Liver Disease: A Physiopathological Approach.

PubMed

Jiménez, José Víctor; Carrillo-Pérez, Diego Luis; Rosado-Canto, Rodrigo; García-Juárez, Ignacio; Torre, Aldo; Kershenobich, David; Carrillo-Maravilla, Eduardo

2017-08-01

Electrolyte and acid-base disturbances are frequent in patients with end-stage liver disease; the underlying physiopathological mechanisms are often complex and represent a diagnostic and therapeutic challenge to the physician. Usually, these disorders do not develop in compensated cirrhotic patients, but with the onset of the classic complications of cirrhosis such as ascites, renal failure, spontaneous bacterial peritonitis and variceal bleeding, multiple electrolyte, and acid-base disturbances emerge. Hyponatremia parallels ascites formation and is a well-known trigger of hepatic encephalopathy; its management in this particular population poses a risky challenge due to the high susceptibility of cirrhotic patients to osmotic demyelination. Hypokalemia is common in the setting of cirrhosis: multiple potassium wasting mechanisms both inherent to the disease and resulting from its management make these patients particularly susceptible to potassium depletion even in the setting of normokalemia. Acid-base disturbances range from classical respiratory alkalosis to high anion gap metabolic acidosis, almost comprising the full acid-base spectrum. Because most electrolyte and acid-base disturbances are managed in terms of their underlying trigger factors, a systematic physiopathological approach to their diagnosis and treatment is required.

Epidemiology and Mortality of Liver Abscess in End-Stage Renal Disease Dialysis Patients: Taiwan National Cohort Study

PubMed Central

Huang, Po-Chang; Wang, Jhi-Joung; Yang, Chun-Ming; Chu, Chin-Chen; Chio, Chung-Ching; Chang, Fu-Lin; Chien, Chih-Chiang

2014-01-01

Background and Objectives To determine the incidence rates and mortality of liver abscess in ESRD patients on dialysis. Design, Setting, Participants, & Measurements Using Taiwan’s National Health Insurance Research Database, we collected data from all ESRD patients who initiated dialysis between 2000 and 2006. Patients were followed until death, end of dialysis, or December 31, 2008. Predictors of liver abscess and mortality were identified using Cox models. Results Of the 53,249 incident dialysis patients identified, 447 were diagnosed as having liver abscesses during the follow-up period (224/100,000 person-years). The cumulative incidence rate of liver abscess was 0.3%, 1.1%, and 1.5% at 1 year, 5 years, and 7 years, respectively. Elderly patients and patients on peritoneal dialysis had higher incidence rates. The baseline comorbidities of diabetes mellitus, polycystic kidney disease, malignancy, chronic liver disease, biliary tract disease, or alcoholism predicted development of liver abscess. Overall in-hospital mortality was 10.1%. Conclusions The incidence of liver abscess is high among ESRD dialysis patients. In addition to the well known risk factors of liver abscess, two other important risk factors, peritoneal dialysis and polycystic kidney disease, were found to predict liver abscess in ESRD dialysis patients. PMID:24551077

Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography.

PubMed

Zhao, Jingxin; Zhai, Fei; Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

2017-01-01

Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis.

Evaluating the Significance of Viscoelasticity in Diagnosing Early-Stage Liver Fibrosis with Transient Elastography

PubMed Central

Cheng, Jun; He, Qiong; Luo, Jianwen; Yang, Xueping; Shao, Jinhua; Xing, Huichun

2017-01-01

Transient elastography quantifies the propagation of a mechanically generated shear wave within a soft tissue, which can be used to characterize the elasticity and viscosity parameters of the tissue. The aim of our study was to combine numerical simulation and clinical assessment to define a viscoelastic index of liver tissue to improve the quality of early diagnosis of liver fibrosis. This is clinically relevant, as early fibrosis is reversible. We developed an idealized two-dimensional axisymmetric finite element model of the liver to evaluate the effects of different viscoelastic values on the propagation characteristics of the shear wave. The diagnostic value of the identified viscoelastic index was verified against the clinical data of 99 patients who had undergone biopsy and routine blood tests for staging of liver disease resulting from chronic hepatitis B infection. Liver stiffness measurement (LSM) and the shear wave attenuation fitting coefficient (AFC) were calculated from the ultrasound data obtained by performing transient elastography. Receiver operating curve analysis was used to evaluate the reliability and diagnostic accuracy of LSM and AFC. Compared to LSM, the AFC provided a higher diagnostic accuracy to differentiate early stages of liver fibrosis, namely F1 and F2 stages, with an overall specificity of 81.48%, sensitivity of 83.33% and diagnostic accuracy of 81.82%. AFC was influenced by the level of LSM, ALT. However, there are no correlation between AFC and Age, BMI, TBIL or DBIL. Quantification of the viscoelasticity of liver tissue provides reliable measurement to identify and differentiate early stages of liver fibrosis. PMID:28107385

Association of Model for End-Stage Liver Disease Score With Mortality in Emergency General Surgery Patients.

PubMed

Havens, Joaquim M; Columbus, Alexandra B; Olufajo, Olubode A; Askari, Reza; Salim, Ali; Christopher, Kenneth B

2016-07-20

Emergency general surgery (EGS) patients have a disproportionate burden of death and complications. Chronic liver disease (CLD) increases the risk of complications following elective surgery. For EGS patients with CLD, long-term outcomes are unknown and risk stratification models do not reflect severity of CLD. To determine whether the Model for End-Stage Liver Disease (MELD) score is associated with increased risk of 90-day mortality following intensive care unit (ICU) admission in EGS patients. We performed a retrospective cohort study of patients with CLD who underwent an EGS procedure based on International Classification of Diseases, Ninth Revision (ICD-9) procedure codes and were admitted to a medical or surgical ICU within 48 hours of surgery between January 1, 1998, and September 20, 2012, at 2 academic medical centers. Chronic liver disease was identified using ICD-9 codes. Multivariable logistic regression was performed. The analysis was conducted from July 1, 2015, to January 1, 2016. The primary outcome was all-cause 90-day mortality. A total of 13 552 EGS patients received critical care; of these, 707 (5%) (mean [SD] age at hospital admission, 56.6 [14.2] years; 64% male; 79% white) had CLD and data to determine MELD score at ICU admission. The median MELD score was 14 (interquartile range, 10-20). Overall 90-day mortality was 30.1%. The adjusted odds ratio of 90-day mortality for each 10-point increase in MELD score was 1.63 (95% CI, 1.34-1.98). A decrease in MELD score of more than 3 in the 48 hours following ICU admission was associated with a 2.2-fold decrease in 90-day mortality (odds ratio = 0.46; 95% CI, 0.22-0.98). In this study, MELD score was associated with 90-day mortality following EGS in patients with CLD. The MELD score can be used as a prognostic factor in this patient population and should be used in preoperative risk prediction models and when counseling EGS patients on the risks and benefits of operative intervention.

Non-alcoholic fatty liver disease: A poorly known pandemic.

PubMed

Augustin, Salvador; Graupera, Isabel; Caballeria, Juan

2017-12-20

Non-alcoholic fatty liver disease (NAFLD) consists of an excessive depositing of fat in the liver, which can end up by causing inflammation, fibrosis and also cirrhosis with the corresponding complications including liver cancer. NAFLD has become the most common liver disease worldwide. The incidence has increased in parallel with the obesity, diabetes and metabolic syndrome epidemic, thus resulting in becoming one of the main indications for liver transplant. The diagnosis has principally been through histology but with the development of non-invasive methods, these have helped in simplifying the management of these patients in clinical practice. The only therapeutic strategies currently available are focused on weight loss (lifestyle changes or bariatric surgery). There is still no approved pharmacological option for the treatment of NAFLD, however there are a number of molecular studies in advanced stages of development. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

The nutritional geometry of liver disease including non-alcoholic fatty liver disease.

PubMed

Simpson, Stephen J; Raubenheimer, David; Cogger, Victoria C; Macia, Laurence; Solon-Biet, Samantha M; Le Couteur, David G; George, Jacob

2018-02-01

Nutrition has a profound effect on chronic liver disease, especially non-alcoholic fatty liver disease (NAFLD). Most observational studies and clinical trials have focussed on the effects of total energy intake, or the intake of individual macronutrients and certain micronutrients, such as vitamin D, on liver disease. Although these studies have shown the importance of nutrition on hepatic outcomes, there is not yet any unifying framework for understanding the relationship between diet and liver disease. The Geometric Framework for Nutrition (GFN) is an innovative model for designing nutritional experiments or interpreting nutritional data that can determine the effects of nutrients and their interactions on animal behaviour and phenotypes. Recently the GFN has provided insights into the relationship between dietary energy and macronutrients on obesity and ageing in mammals including humans. Mouse studies using the GFN have disentangled the effects of macronutrients on fatty liver and the gut microbiome. The GFN is likely to play a significant role in disentangling the effects of nutrients on liver disease, especially NAFLD, in humans. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease.

PubMed

Irvine, Katharine M; Wockner, Leesa F; Shanker, Mihir; Fagan, Kevin J; Horsfall, Leigh U; Fletcher, Linda M; Ungerer, Jacobus P J; Pretorius, Carel J; Miller, Gregory C; Clouston, Andrew D; Lampe, Guy; Powell, Elizabeth E

2016-03-01

Current tools for risk stratification of chronic liver disease subjects are limited. We aimed to determine whether the serum-based ELF (Enhanced Liver Fibrosis) test predicted liver-related clinical outcomes, or progression to advanced liver disease, and to compare the performance of ELF to liver biopsy and non-invasive algorithms. Three hundred patients with ELF scores assayed at the time of liver biopsy were followed up (median 6.1 years) for liver-related clinical outcomes (n = 16) and clear evidence of progression to advanced fibrosis (n = 18), by review of medical records and clinical data. Fourteen of 73 (19.2%) patients with ELF score indicative of advanced fibrosis (≥9.8, the manufacturer's cut-off) had a liver-related clinical outcome, compared to only two of 227 (<1%) patients with ELF score <9.8. In contrast, the simple scores APRI and FIB-4 would only have predicted subsequent decompensation in six and four patients respectively. A unit increase in ELF score was associated with a 2.53-fold increased risk of a liver-related event (adjusted for age and stage of fibrosis). In patients without advanced fibrosis on biopsy at recruitment, 55% (10/18) with an ELF score ≥9.8 showed clear evidence of progression to advanced fibrosis (after an average 6 years), whereas only 3.5% of those with an ELF score <9.8 (8/207) progressed (average 14 years). In these subjects, a unit increase in ELF score was associated with a 4.34-fold increased risk of progression. The ELF score is a valuable tool for risk stratification of patients with chronic liver disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Liver diseases in the elderly].

PubMed

Bruguera, Miguel

2014-11-01

Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Three-dimensional printing and pediatric liver disease.

PubMed

Alkhouri, Naim; Zein, Nizar N

2016-10-01

Enthusiastic physicians and medical researchers are investigating the role of three-dimensional printing in medicine. The purpose of the current review is to provide a concise summary of the role of three-dimensional printing technology as it relates to the field of pediatric hepatology and liver transplantation. Our group and others have recently demonstrated the feasibility of printing three-dimensional livers with identical anatomical and geometrical landmarks to the native liver to facilitate presurgical planning of complex liver surgeries. Medical educators are exploring the use of three-dimensional printed organs in anatomy classes and surgical residencies. Moreover, mini-livers are being developed by regenerative medicine scientist as a way to test new drugs and, eventually, whole livers will be grown in the laboratory to replace organs with end-stage disease solving the organ shortage problem. From presurgical planning to medical education to ultimately the bioprinting of whole organs for transplantation, three-dimensional printing will change medicine as we know in the next few years.

Adult Liver Cancer Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

Cancer.gov

Hepatocellular carcinoma is the most common type of adult primary liver cancer. The Barcelona Clinical Liver Cancer (BCLC) Staging System is used to stage liver cancer. Learn more about risk factors, signs and symptoms, tests to diagnose, prognosis, and stages of adult primary liver cancer.

Magnetic Resonance Imaging and Liver Histology as Biomarkers of Hepatic Steatosis in Children with Nonalcoholic Fatty Liver Disease

PubMed Central

Schwimmer, Jeffrey B.; Middleton, Michael S.; Behling, Cynthia; Newton, Kimberly P.; Awai, Hannah I.; Paiz, Melissa N.; Lam, Jessica; Hooker, Jonathan C.; Hamilton, Gavin; Fontanesi, John; Sirlin, Claude B.

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI-estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. MRI-estimated liver PDFF was significantly (p < 0.01) correlated (0.725) with steatosis grade. Correlation of MRI-estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (p<0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly (p<0.01) weaker in children with stage 2–4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI-estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. Conclusions Advanced magnitude-based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus magnitude-based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child. PMID:25529941

Portopulmonary Hypertension in Liver Disease Presenting in Childhood.

PubMed

Ecochard-Dugelay, Emmanuelle; Lambert, Virginie; Schleich, Jean-Marc; Duché, Mathieu; Jacquemin, Emmanuel; Bernard, Olivier

2015-09-01

Portopulmonary hypertension (POPH) is a known complication of cirrhosis in adults, but there is little information on its incidence and outcome in children with liver disease. We report 14 patients with POPH and present a synthesis of the medical literature. Diagnosis of POPH in the 14 patients was based on right-sided heart catheterization displaying mean pulmonary artery pressure (mPAP) >25 mmHg, indexed pulmonary vascular resistances >3 Wood units · m, and pulmonary wedge pressure <15 mmHg. A literature review added 84 patients. In our unit, POPH was found in 0.5% of the children with portal hypertension, 0.9% of the children with end-stage liver disease awaiting transplantation, and 3 children with congenital portosystemic shunts (CPSSs). Analysis of 98 reported patients, including the 14 presented here, showed the cause of liver disease to be chronic liver disease or portal cavernoma in 76 instances (34 with a history of surgical portosystemic shunt) and CPSS in 22 instances. There was a precession with proven hypoxemia caused by hepatopulmonary syndrome in 6 patients. Median survival was 3 months in 56 untreated patients. An 80% 5-year probability of survival in 42 patients was treated by CPSS closure, pulmonary vasodilators, and/or liver transplantation. Mean pretransplant mPAP was 34 and 49 mmHg in transplant survivors and nonsurvivors, respectively. POPH is a rare but extremely severe complication of childhood liver disease. Portosystemic shunts, whether congenital or acquired, likely play an important causative role. Early diagnosis is crucial and requires systematic screening by echocardiography in children at risk.

Comparison of acoustic radiation force impulse imaging (ARFI) to liver biopsy histologic scores in the evaluation of chronic liver disease: A pilot study.

PubMed

Haque, Mazhar; Robinson, Charlotte; Owen, David; Yoshida, Eric M; Harris, Alison

2010-01-01

Acoustic Radiation Force Impulse Imaging (ARFI) is a novel non invasive technique studying the localized mechanical properties of tissue by utilising short, high intensity acoustic pulses (shear wave pulses) to assess the mechanical response (tissue displacement), providing a measure of tissue elasticity. The aim of this study is to investigate the feasibility of ARFI imaging as a non-invasive method for the assessment of liver fibrosis compared to liver biopsy scores. A prospective blind comparison study of ARFI elastography (Virtual Touch Imaging., ACUSON S2000 Ultrasound Unit, Siemens, Mountain View CA) in a consecutive series of patients who underwent liver biopsy for assessment of fibrosis in chronic liver disease. ARFI shear-wave propagation velocity was measured in meters per second. Mean ARFI velocities were compared with both Batts-Ludwig (F0 to F4) and Modified Ishak scores (F0 to F4) for fibrosis in liver biopsy findings. Twenty-one patients with chronic liver disease (Hepatitis C (HCV) =16, Hepatitis B (HBV) = 1, both HCV and HBV = 1 Alcoholic liver disease (ALD) = 1, others = 2) underwent ARFI and liver biopsy on the same day. The Spearman correlation coefficients between the median values of the ARFI measurements and the histological fibrosis stage of the Modified Ishak score and Batts-Lud- (3) wig score were both highly significant (p < 0.01) with rho = 0.69 and rho = 0.72 respectively. The median ARFI (total 180 replications; minimum 5, maximum 10 measurements per patients) velocities for our study population range from 0.92 to 4.17 m/sec. Areas under the receiver operating characteristic curve for the accuracy of ARFI imaging was 1.00 and 0.35, for the diagnosis of moderate fibrosis (histologic fibrosis stage, F (3) 2) and 0.85 and 0.85 respectively for Ishak and Batts-Ludwig score, for the diagnosis of cirrhosis. ARFI imaging has a strong correlation with the fibrosis stage of both Batts-Ludwig and shak score in chronic liver disease. It

Extracorporeal Bioartificial Liver for Treating Acute Liver Diseases

PubMed Central

Kumar, Ashok; Tripathi, Anuj; Jain, Shivali

2011-01-01

Abstract: Liver is a vital organ of the human body performing myriad of essential functions. Liver-related ailments are often life-threatening and dramatically deteriorate the quality of life of patients. Management of acute liver diseases requires adequate support of various hepatic functions. Thus far, liver transplantation has been proven as the only effective solution for acute liver diseases. However, broader application of liver transplantation is limited by demand for lifelong immunosuppression, shortage of organ donors, relative high morbidity, and high cost. Therefore, research has been focused on attempting to develop alternative support systems to treat liver diseases. Earlier attempts have been made to use nonbiological therapies based on the use of conventional detoxification procedures such as filtration and dialysis. However, the absence of liver cells in such techniques reduced the overall survival rate of the patients and led to inadequate essential liver-specific functions. As a result, there has been growing interest in the development of biological therapy-based extracorporeal liver support systems as a bridge to liver transplantation or to support the ailing liver. A bioartificial liver support is an extracorporeal device through which plasma is circulated over living and functionally active hepatocytes packed in a bioreactor with the aim to aid the diseased liver until it regenerates or until a suitable graft for transplantation is available. This review article gives a brief overview of efficacy of various liver support systems that are currently available. Also, the development of advanced liver support systems, which has been analyzed for improving the important system component such as cell source and other culture and circulation conditions for the maintenance of the liver-specific functions, have been described. PMID:22416599

Non-alcoholic fatty liver disease: Pathophysiology and management

PubMed Central

Carr, Rotonya M.; Oranu, Amanke; Khungar, Vandana

2016-01-01

Abstract/Summary NAFLD is an important cause of morbidity and mortality worldwide both because of cardiovascular, hepatic and oncologic sequelae as well as because it is rapidly becoming the leading cause of end stage liver disease and liver transplant. With a prevalence of 30% in the US, it has reached epidemic proportions. While the metabolic syndrome is a common risk factor, there are differences among racial and ethnic groups, suggesting the complex interaction between hormonal, nutritional and genetic factors at play in disease pathogenesis. The clinical syndrome of NAFLD spans from bland steatosis to steatohepatitis which can progress to fibrosis and cirrhosis. The pathogenesis including roles of hormones, nutritional and intestinal dysbiosis, insulin resistance, lipotoxicity, and hepatic inflammation, and genes are examined. Non-invasive testing and liver biopsy indications are reviewed. Approved and investigational therapies for NAFLD and NASH are outlined in this review of a disease that is currently an area of great interest to the hepatology community. PMID:27837778

An epidemiological study of the association of coffee with chronic liver disease.

PubMed

Walton, H B; Masterton, G S; Hayes, P C

2013-11-01

Chronic liver disease affects 855 people per million in the UK. Previous studies have reported that coffee appears protective against the development of abnormal liver enzymes, hepatic fibrosis and cirrhosis. The aim of this study, the first in a Scottish population, was to compare coffee consumption in patients with liver disease and that of control populations to determine correlations between coffee intake and the incidence of non-cancerous liver disease and with Child's-Pugh and model for end-stage liver disease (MELD) scores. Two hundred and eighty-six patients attending the liver outpatient department at the Royal Infirmary of Edinburgh completed a questionnaire regarding coffee consumption and lifestyle factors. Control questionnaires were also completed by 100 orthopaedic outpatients and 120 medical students. Patients with cirrhosis (n = 95) drank significantly less coffee than those without cirrhosis (p = <0.001). There was no correlation between Child's-Pugh (-0.018) and MELD scores (-0.132) with coffee consumption. Coffee drinking is associated with a reduced prevalence of cirrhosis in patients with chronic liver disease. However, there was no significant difference in the amount of coffee drunk by liver patients and the control groups. It is possible that by changing the amount of coffee drunk, the development of cirrhosis in liver disease could be postponed.

New Discriminant Method for Identifying the Aggressive Disease Phenotype of Non-alcoholic Fatty Liver Disease.

PubMed

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

2017-01-01

Objective To detect the aggressive phenotype (AP) of non-alcoholic fatty liver disease (NAFLD) based on the initial laboratory data and clinical characteristics. Methods We enrolled 144 patients with histologically proven NAFLD. For the first analysis, 24 NAFLD patients underwent repeat biopsy to establish a discriminant formula for predicting the AP of NAFLD (D-APN). The AP was defined by NAFLD that had been maintained or progressed to a fibrotic stage beyond stage 2. In the second analysis, we analyzed the distribution of the AP in each stage of disease and the incidence of the PNPLA3 rs738409 GG genotype in AP in 120 other patients. Results After the analysis, the following function was found to discriminate the disease phenotype: z=0.150×body mass index (kg/m 2 )+0.085×age (years)+1.112×ln (AST) (IU/L)+0.127×ln (m-AST)-12.96. A positive result indicates the AP of NAFLD. The discriminant functions had a positive predictive value of 94% and a negative predictive value of 71%. The distribution of the AP and the incidence of the PNPLA3 GG genotype in the AP in each stage of the disease among the 120 patients were as follows: non-alcoholic fatty liver, 30%/33%; non-alcoholic steatohepatitis (NASH) stage 1, 53%/26%; stage 2, 71%/70%; stage 3, 92%/57%; and stage 4, 93%/64%; there was a significant increase in the incidence of the AP as the disease progressed (p<0.001). Conclusion The new discriminant formula was useful for predicting disease progression potential in NAFLD patients and the incidence of the PNPLA3 GG genotype was elevated according to the distribution of AP.

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

PubMed

Mansoor, Sana; Collyer, Elizabeth; Alkhouri, Naim

2015-06-01

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

Enzymatic liver function capacity correlates with disease severity of patients with liver cirrhosis: a study with the LiMAx test.

PubMed

Malinowski, Maciej; Jara, Maximilian; Lüttgert, Katja; Orr, James; Lock, Johan Friso; Schott, Eckart; Stockmann, Martin

2014-12-01

Assessment and quantification of actual liver function is crucial in patients with chronic liver disease to monitor disease progression and predict individual prognosis. Mathematical models, such as model for end-stage liver disease, are used for risk stratification of patients with chronic liver disease but do not include parameters that reflect the actual functional state of the liver. We aimed to evaluate the potential of a (13)C-based liver function test as a stratification tool by comparison with other liver function tests and clinical parameters in a large sample of healthy controls and cirrhotic patients. We applied maximum liver function capacity (LiMAx) to evaluate actual liver function in 347 patients with cirrhosis and in 86 controls. LiMAx showed strong negative correlation with Child-Pugh Score (r = -0.707; p < 0.001), MELD (r = -0.686; p < 0.001) and liver function tests. LiMAx was lower in patients with liver cirrhosis compared to healthy controls [99 (57-160) µg/kg/h vs. 412 (365-479) µg/kg/h, p < 0.001] and differed among Child-Pugh classes [a: 181 (144-227) µg/kg/h, b: 96 (62-132) µg/kg/h and c: 52 (37-81) µg/kg/h; p < 0.001]. When stratified patients according to disease severity, LiMAx results were not different between cirrhotic patients and cirrhotic patients with transjugular intrahepatic portosystemic shunt. LiMAx appears to provide reliable information on remnant enzymatic liver function in chronic liver disease and allows graduation of disease severity.

Preoperative selective desensitization of live donor liver transplant recipients considering the degree of T lymphocyte cross-match titer, model for end-stage liver disease score, and graft liver volume.

PubMed

Hong, Geun; Yi, Nam-Joon; Suh, Suk-won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Lee, Kyungbun; Lee, Kwang-Woong; Park, Myoung Hee; Suh, Kyung-Suk

2014-05-01

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.

Metabonomics Research Progress on Liver Diseases.

PubMed

Yu, Mengqian; Zhu, Ying; Cong, Qingwei; Wu, Chunyan

2017-01-01

Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases.

PET/CT with 18F Fluorocholine as an Imaging Biomarker for Chronic Liver Disease: A Preliminary Radiopathologic Correspondence Study in Patients with Liver Cancer.

PubMed

Kwee, Sandi A; Wong, Linda; Chan, Owen T M; Kalathil, Sumodh; Tsai, Naoky

2018-04-01

Purpose To determine the relationship between hepatic uptake at preoperative fluorine 18 ( 18 F) fluorocholine combined positron emission tomography (PET) and computed tomography (CT) and the histopathologic features of chronic liver disease in patients with Child-Pugh class A or B disease who are undergoing hepatic resection for liver cancer. Materials and Methods Forty-eight patients with resectable liver tumors underwent preoperative 18 F fluorocholine PET/CT. Mean liver standardized uptake value (SUV mean ) measurements were obtained from PET images, while histologic indexes of inflammation and fibrosis were applied to nontumor liver tissue from resection specimens. Effects of histopathologic features on liver SUV mean were examined with analysis of variance. Results Liver SUV mean ranged from 4.3 to 11.6, correlating significantly with Knodell histologic activity index (ρ = -0.81, P < .001) and several clinical indexes of liver disease severity. Liver SUV mean also differed significantly across groups stratified by necroinflammatory severity and Metavir fibrosis stage (P < . 001). The area under the receiver operating characteristic curve for 18 F fluorocholine PET/CT detecting Metavir fibrosis stage F1 or higher was 0.89 ± 0.05, with an odds-ratio of 3.03 (95% confidence interval: 1.59, 5.88) and sensitivity and specificity of 82% and 93%, respectively. Conclusion Correlations found in patients undergoing hepatic resection for liver cancer between liver 18 F fluorocholine uptake and histopathologic indexes of liver fibrosis and inflammation support the use of 18 F fluorocholine PET/CT as a potential imaging biomarker for chronic liver disease. © RSNA, 2018.

Liver cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study.

PubMed

Momin, Behnoosh R; Pinheiro, Paulo S; Carreira, Helena; Li, Chunyu; Weir, Hannah K

2017-12-15

Worldwide, liver cancer is a leading cause of death for both men and women. The number of Americans who are diagnosed with and die of liver cancer has been rising slowly each year. Using data from the CONCORD-2 study, this study examined population-based survival by state, race, and stage at diagnosis. Data from 37 statewide registries, which covered 81% of the US population, for patients diagnosed during 2001-2009 were analyzed. Survival up to 5 years was adjusted for background mortality (net survival) with state- and race-specific life tables, and it was age-standardized with the International Cancer Survival Standard weights. Liver cancer was diagnosed overall more often at the localized stage, with blacks being more often diagnosed at distant and regional stages than whites. 5-year net survival was 12.2% in 2001-2003 and 14.8% in 2004-2009. Whites had higher survival than blacks in both calendar periods (11.7% vs 9.1% and 14.3% vs 11.4%, respectively). During 2004-2009, 5-year survival was 25.7% for localized-stage disease, 9.5% for regional-stage disease, and 3.5% for distant-stage disease. Some progress has occurred in survival for patients with liver cancer, but 5-year survival remains low, even for those diagnosed at the localized stage. Efforts directed at controlling well-established risk factors such as hepatitis B may have the greatest impact on reducing the burden of liver cancer in the United States. Cancer 2017;123:5059-78. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS

PubMed Central

Bartlett, Jaclyn R.; Friedman, Kenneth J.; Ling, Simon C.; Pace, Rhonda G.; Bell, Scott C.; Bourke, Billy; Castaldo, Giuseppe; Castellani, Carlo; Cipolli, Marco; Colombo, Carla; Colombo, John L.; Debray, Dominique; Fernandez, Adriana; Lacaille, Florence; Macek, Milan; Rowland, Marion; Salvatore, Francesco; Taylor, Christopher J.; Wainwright, Claire; Wilschanski, Michael; Zemková, Dana; Hannah, William B.; Phillips, M. James; Corey, Mary; Zielenski, Julian; Dorfman, Ruslan; Wang, Yunfei; Zou, Fei; Silverman, Lawrence M.; Drumm, Mitchell L.; Wright, Fred A.; Lange, Ethan M.; Durie, Peter R.; Knowles, Michael R.

2013-01-01

Context A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension. Objective To assess whether any of 9 polymorphisms in 5 candidate genes (SERPINA1, ACE, GSTP1, MBL2, and TGFB1) are associated with severe liver disease in CF patients. Design, Setting, and Participants A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls. Main Outcome Measures We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD. Results The initial study showed CFLD to be associated with the SERPINA1 (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10−6; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (TGFB1) codon 10 CC genotype (P=2.8×10−3; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the SERPINA1 Z allele (P=1.4×10−3; OR 3.42, CI 1.54–7.59), but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (P=1.5×10−8; OR 5.04, CI 2.88–8.83). Conclusion The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension. PMID:19738092

Alcoholic liver disease confers a worse prognosis than HCV infection and non-alcoholic fatty liver disease among patients with cirrhosis: An observational study

PubMed Central

Marot, Astrid; Henrion, Jean; Knebel, Jean-François; Moreno, Christophe

2017-01-01

Background Cirrhosis is a heterogeneous clinical condition that includes patients at wide-ranging stages of severity. The role of the underlying liver disease on patient prognosis remains unclear. Aim To assess the impact of the underlying liver disease on the occurrence of hepatocellular carcinoma (HCC) and death. Methods Data related to the occurrence of HCC and death were collected during a 21-year period among patients with cirrhosis related to alcoholic liver disease (ALD) (n = 529), chronic hepatitis C virus (HCV) infection (n = 145) or non-alcoholic fatty liver disease (NAFLD) (n = 78). Results At inclusion, ALD patients were younger than HCV and NAFLD patients (56 vs. 67 vs. 63 years; p<0.001) and had worse liver function (percent of patients with Child-Pugh stages B or C: 48% vs. 8% vs. 17%; p<0.001). During follow-up, 85 patients developed HCC and 379 died. The 10-year cumulative incidence rate of HCC was lower in ALD patients than in HCV and NAFLD patients (8.4% vs. 22.0% vs. 23.7%; p<0.001). The 10-year cumulative incidence rates of mortality were not statistically different between ALD, HCV and NAFLD patients (58.1% vs. 47.7% vs. 49.9%; p = 0.078). Alcohol abstinence and viral eradication were associated with reduced mortality among ALD and HCV patients, respectively. In multivariate analyses, ALD was associated with a reduced risk of HCC (0.39; 95% CI, 0.20–0.76; p = 0.005) but with a higher risk of mortality (1.53; 95% CI, 1.20–1.95; p<0.001). ALD patients died more frequently from decompensation of cirrhosis. Conclusion Despite a lower incidence of HCC, patients with ALD-related cirrhosis have a worse outcome than those with chronic HCV infection or NAFLD-related cirrhosis. PMID:29077714

Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years.

PubMed

Federico, Alessandro; Dallio, Marcello; Loguercio, Carmelina

2017-01-24

Silymarin is the extract of Silybum marianum , or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.

Altered plasma lipidome profile of dairy cows with fatty liver disease.

PubMed

Gerspach, C; Imhasly, S; Gubler, M; Naegeli, H; Ruetten, M; Laczko, E

2017-02-01

Fatty liver disease is a common health problem of dairy cows occurring during the transition from pregnancy to lactation. It is a direct response to fat mobilization due to negative energy balance. Accumulation of lipids in the liver occurs if the uptake of non-esterified fatty acids by the liver exceeds the capacity of lipid oxidation or secretion by the liver. Currently, the diagnosis of fatty liver disease requires confirmation through biopsies to determine the hepatic lipid content. In view of this lack of a practical diagnostic tool, we compared the plasma lipidome of diseased dairy cows using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Multivariate data analysis yielded 20 m/z values that were able to distinguish between dairy cows with no hepatic lipidosis and those exhibiting different stages of the disease. Based on the chromatography retention time and m/z ratios, we identified phosphatidylcholines with reduced plasma abundances in cows with fatty liver disease. The abundances of different bile acids tended to be increased. In addition, we detected two metabolites related to inflammation, resolvin E1 and palmitoyl-ethanolamine (PEA), which need to be further investigated in cattle. These results indicate that the measurement of specific representatives of phosphatidylcholines in plasma may provide a novel diagnostic biomarker of fatty liver disease in dairy cows. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity.

PubMed

Pavlides, Michael; Banerjee, Rajarshi; Tunnicliffe, Elizabeth M; Kelly, Catherine; Collier, Jane; Wang, Lai Mun; Fleming, Kenneth A; Cobbold, Jeremy F; Robson, Matthew D; Neubauer, Stefan; Barnes, Eleanor

2017-07-01

The diagnosis of non-alcoholic steatohepatitis and fibrosis staging are central to non-alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non-alcoholic steatohepatitis and fibrosis using histology as standard in non-alcoholic fatty liver disease. Seventy-one patients with suspected non-alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score (LIF 0-4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non-alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ≥2 and/or Fibrosis ≥2 as defined by the Fatty Liver Inhibition of Progression consortium) non-alcoholic fatty liver disease. Transient elastography was also performed. Magnetic resonance success rate was 95% vs 59% for transient elastography (P<.0001). Fibrosis stage on biopsy correlated with liver inflammation and fibrosis (r s =.51, P<.0001). The area under the receiver operating curve using liver inflammation and fibrosis for the diagnosis of cirrhosis was 0.85. Liver inflammation and fibrosis score for ballooning grades 0, 1 and 2 was 1.2, 2.7 and 3.5 respectively (P<.05) with an area under the receiver operating characteristic curve of 0.83 for the diagnosis of ballooning. Patients with steatosis had lower liver inflammation and fibrosis (1.3) compared to patients with non-alcoholic steatohepatitis (3.0) (P<.0001); area under the receiver operating characteristic curve for the diagnosis of non-alcoholic steatohepatitis was 0.80. Liver inflammation and fibrosis scores for patients with mild and significant non-alcoholic fatty liver disease were 1.2 and 2.9 respectively (P<.0001). The area under the receiver operating characteristic curve of liver inflammation and fibrosis for the diagnosis of significant non-alcoholic fatty liver disease was 0

Vitamin D Deficiency and Its Relationship with Child-Pugh Class in Patients with Chronic Liver Disease

PubMed Central

Jamil, Zubia; Arif, Sharmin; Khan, Anum; Durrani, Asghar Aurangzeb; Yaqoob, Nayyar

2018-01-01

Abstract Background and Aims: Skeletal manifestation in liver diseases represents the minimally scrutinized part of the disease spectrum. Vitamin D deficiency has a central role in developing hepatic osteodystrophy in patients with chronic liver disease. This study aimed to investigate vitamin D levels and their relationship with disease advancement in these patients. Methods: Vitamin D levels were checked in 125 chronic liver disease patients. The patients were classified in three stages according to Child-Pugh score: A, B and C. The relationship of vitamin D levels with Child-Pugh score and other variables in the study was assessed by the contingency coefficient. Correlation and logistic regression analyses were also carried out to find additional predictors of low vitamin D levels. Results: Among the patients, 88% had either insufficient or deficient stores of vitamin D, while only 12% had sufficient vitamin D levels (p >0.05). Vitamin D levels were notably related to Child-Pugh class (contingency coefficient = 0.5, p <0.05). On univariate and multinomial regression analyses, age, female sex, MELD and Child-Pugh class were predictors of low vitamin D levels. Age, model of end-stage liver disease score and Child-Pugh score were negatively correlated to vitamin D levels (p <0.05). Conclusions: Vitamin D deficiency is notably related to age, female sex and model of end-stage liver disease score, in addition to Child-Pugh class of liver cirrhosis. Vitamin D levels should be routinely checked in patients with advanced liver cirrhosis (Child-Pugh class B and C) and this deficiency must be addressed in a timely manner to improve general well-being of cirrhotic patients.

Emricasan Improves Liver Function in Patients With Cirrhosis and High Model for End-stage Liver Disease Scores Compared With Placebo.

PubMed

Frenette, Catherine T; Morelli, Giuseppe; Shiffman, Mitchell L; Frederick, R Todd; Rubin, Raymond A; Fallon, Michael B; Cheng, Jason T; Cave, Matt; Khaderi, Saira A; Massoud, Omar; Pyrsopoulos, Nikolaos; Park, James S; Robinson, James M; Yamashita, Mason; Spada, Alfred P; Chan, Jean L; Hagerty, David T

2018-06-15

Caspase-mediated apoptosis and inflammation contribute to progression of liver disease. Emricasan is a pan-caspase inhibitor that reduced serum markers of apoptosis and liver inflammation in patients with hepatitis C and non-alcoholic steatohepatitis (NASH). We performed a multicenter study of 86 patients with cirrhosis (Child-Pugh class A or B; mean score, 6.9; 38% with alcohol-associated cirrhosis, 29% with HCV-associated cirrhosis, and 23% with NASH) and model for end-stage liver disease (MELD) scores of 11-18 (mean, 12.8). Patients were randomly assigned to groups given placebo (n=42) or emricasan (25 mg, n=44), twice daily for 3 months; subjects then received open-label emricasan (25 mg) twice-daily for 3 months. The primary endpoint was the change from baseline in serum levels of cleaved keratin 18 (CK-18) at month 3. Seventy-four patients completed the 3-month study period (40 given emricasan and 34 given placebo); 69 patients received open-label emricasan for 3 months afterward. At the 3-month timepoint, emricasan significantly reduced mean MELD (P=.003) and Child-Pugh (P=.003) scores in subjects with high MELD scores (15 or more), compared with placebo, with significant reductions in INR (95% CI, -0.2882 to -0.0866) and total bilirubin (95% CI, -1.5069 to -0.0823) vs placebo. There were no significant differences between emricasan and placebo groups in mean MELD (P=.466) or Child-Pugh (P=.124) scores overall at 3 months compared to placebo. Of patients with high MELD scores, 6/9 given emricasan (67%) had a reduction of 2 points or more at month 3, compared with 2/10 given placebo (20%). Serum levels of full-length CK-18 (P=.02) and caspase 3/7 (P<.001), but not cleaved CK-18 (P=.092), decreased significantly at 3 months in the emricasan vs placebo group. Emricasan was well tolerated, and adverse events were balanced between groups. Emricasan's effects were generally maintained or increased after 6 months of treatment. In a randomized trial of patients with

A whole-killed, blood-stage lysate vaccine protects against the malaria liver stage.

PubMed

Lu, X; Liu, T; Zhu, F; Chen, L; Xu, W

2017-01-01

Although the attenuated sporozoite is the most efficient vaccine to prevent infection with the malaria parasite, the limitation of a source of sterile sporozoites greatly hampers its application. In this study, we found that the whole-killed, blood-stage lysate vaccine could confer protection against the blood stage as well as the liver stage. Although the protective immunity induced by the whole-organism vaccine against the blood stage is dependent on parasite-specific CD4 + T-cell responses and antibodies, in mice immunized with the whole-killed, blood-stage lysate vaccine, CD8 + , but not CD4 + effector T-cell responses greatly contributed to protection against the liver stage. Thus, our data suggested that the whole-killed, blood-stage lysate vaccine could be an alternative promising strategy to prevent malaria infection and to reduce the morbidity and mortality of patients with malaria. © 2016 John Wiley & Sons Ltd.

Liver-inherent immune system: its role in blood-stage malaria

PubMed Central

Wunderlich, Frank; Al-Quraishy, Saleh; Dkhil, Mohamed A.

2014-01-01

The liver is well known as that organ which is obligately required for the intrahepatocyte development of the pre-erythrocytic stages of the malaria-causative agent Plasmodium. However, largely neglected is the fact that the liver is also a central player of the host defense against the morbidity- and mortality-causing blood stages of the malaria parasites. Indeed, the liver is equipped with a unique immune system that acts locally, however, with systemic impact. Its main “antipodal” functions are to recognize and to generate effective immunoreactivity against pathogens on the one hand, and to generate tolerance to avoid immunoreactivity with “self” and harmless substances as dietary compounds on the other hand. This review provides an introductory survey of the liver-inherent immune system: its pathogen recognition receptors including Toll-like receptors (TLRs) and its major cell constituents with their different facilities to fight and eliminate pathogens. Then, evidence is presented that the liver is also an essential organ to overcome blood-stage malaria. Finally, we discuss effector responses of the liver-inherent immune system directed against blood-stage malaria: activation of TLRs, acute phase response, phagocytic activity, cytokine-mediated pro- and anti-inflammatory responses, generation of “protective” autoimmunity by extrathymic T cells and B-1 cells, and T cell-mediated repair of liver injuries mainly produced by malaria-induced overreactions of the liver-inherent immune system. PMID:25408684

Significance of increased expression of decoy receptor 3 in chronic liver disease.

PubMed

Kim, S; Kotoula, V; Hytiroglou, P; Zardavas, D; Zhang, L

2009-08-01

Considerable evidence has indicated that apoptosis plays an important role in hepatocyte death in chronic liver disease. However, the cellular and molecular mechanisms underlying liver regeneration in these diseases are largely unknown. Plausibly, certain molecules expressed to counteract apoptosis might provide survival advantage of certain liver cells. Therefore, we investigated a possible expression of decoy receptor 3 of the tumour necrosis factor receptor family in chronic liver diseases since decoy receptor 3 is known to inhibit apoptosis mediated by pro-apoptotic tumour necrosis factor family ligands including Fas ligand. A series of liver biopsies from patients with different stages of fibrosis were subjected to immunohistochemistry and in situ hybridization. Both decoy receptor 3 protein and mRNA were mainly expressed in biliary epithelial cells and infiltrating lymphocytes in the diseased livers. Most noticeably, intense decoy receptor 3 expression was observed in newly developing biliary ductules in regenerative nodules as well as dysplastic nodules of cirrhotic livers. In addition, decoy receptor 3 secretion in hepatocellular carcinoma cells in culture was via the activation of mitogen-activated protein kinases. Decoy receptor 3 was specifically expressed in chronic liver diseases and hepatocellular carcinoma cells, and decoy receptor 3 might facilitate the survival of liver cells by exerting its anti-apoptotic activity during the progression of liver cirrhosis and hepatocarcinogenesis.

Serum endocan levels in patients with chronic liver disease

PubMed Central

Tok, Duran; Ekiz, Fuat; Basar, Omer; Coban, Sahin; Ozturk, Gulfer

2014-01-01

Background and Aim: Early detection of fibrosis should be the main goal of treatment in liver cirrhosis. Endocan, previously called endothelial cell specific molecule-1, is expressed by endothelial cells, primarily in the lung, liver and kidney. In this study, we aimed to examine the correlation of liver fibrosis stage, histological activity and grade of steatosis between serum levels of endocan in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Patients and Methods: This cross-sectional study includes a total of 146 subjects. 55 CHB patients, 19 CHC patients, 38 NAFLD patients and 34 healthy controls were enrolled consecutively. Liver biopsies were performed in all patients with chronic viral hepatitis. NAFLD patients had either grade 2 or grade 3 steatosis on ultrasonography and elevated liver enzymes above the upper normal limits. Serum endocan levels were assessed from blood samples obtained at admission. Results: Gender distribution was similar among the groups (p=0.056). The mean age of the CHB patients was 45.8±12.1, CHC patients was 55.0±12.8 years, NAFLD patients was 42.8±10.8, while control group was 39.4±13.6 years old. Patients with CHC were older than all the others (p=0.001). Serum endocan levels were statistically significantly lower in CHB, CHC and NAFLD groups when compared with controls. Although levels of endocan were lower in CHB and CHC groups when compared with NAFLD group, the difference was not statistically significant. Conclusion: Serum endocan concentrations decrease in patients with liver disease. Unlike previous studies, we showed a negative correlation between endocan levels and inflammation stage of chronic hepatitis. However, further studies are needed to establish the association between endocan levels, liver fibrosis and hepatic inflammation. PMID:25126183

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.

Gut microbiome and liver diseases.

PubMed

Tilg, Herbert; Cani, Patrice D; Mayer, Emeran A

2016-12-01

The gut microbiota has recently evolved as a new important player in the pathophysiology of many intestinal and extraintestinal diseases. The liver is the organ which is in closest contact with the intestinal tract, and is exposed to a substantial amount of bacterial components and metabolites. Various liver disorders such as alcoholic liver disease, non-alcoholic liver disease and primary sclerosing cholangitis have been associated with an altered microbiome. This dysbiosis may influence the degree of hepatic steatosis, inflammation and fibrosis through multiple interactions with the host's immune system and other cell types. Whereas few results from clinical metagenomic studies in liver disease are available, evidence is accumulating that in liver cirrhosis an oral microbiome is overrepresented in the lower intestinal tract, potentially contributing to disease process and severity. A major role for the gut microbiota in liver disorders is also supported by the accumulating evidence that several complications of severe liver disease such as hepatic encephalopathy are efficiently treated by various prebiotics, probiotics and antibiotics. A better understanding of the gut microbiota and its components in liver diseases might provide a more complete picture of these complex disorders and also form the basis for novel therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Nonalcoholic fatty liver disease: diagnosis, pathogenesis, and management.

PubMed

Başaranoğlu, Metin; Örmeci, Necati

2014-04-01

Nonalcoholic fatty liver disease (NAFLD) is an umbrella term that covers both a relatively benign condition, which is simple steatosis, and nonalcoholic steatohepatitis (NASH). NASH is characterized by a chronic and progressive liver pathology that may progress to cirrhosis, end-stage liver disease, hepatocellular carcinoma, and liver transplantation. Despite the growing body of evidence, one of the important and unresolved problems is the pathogenesis of NASH. It might be a metabolic disturbance as a primary abnormality in NAFLD. Insulin resistance is at the center of these metabolic abnormalities. Then, hepatocyte injury might be induced by oxidative stress. This ongoing process progresses to NASH, even to cirrhosis in some patients. In addition to oxidative stress, possibilities for the next hit are lipid peroxidation, reactive metabolites, adipose tissue products, transforming growth factor-β₁, Fas ligand, mitochondrial dysfunction, respiratory chain deficiency, and intestinal microbiota. Currently, there is no well-established and approved therapy. Recommendations are to improve existing co-morbidities, such as obesity, hyperlipidemia, or type 2 diabetes, and lifestyle modification with weight loss and exercise.

Increase of infiltrating monocytes in the livers of patients with chronic liver diseases.

PubMed

Huang, Rui; Wu, Hongyan; Liu, Yong; Yang, Chenchen; Pan, Zhiyun; Xia, Juan; Xiong, Yali; Wang, Guiyang; Sun, Zhenhua; Chen, Jun; Yan, Xiaomin; Zhang, Zhaoping; Wu, Chao

2016-01-01

Infiltrating monocytes have been demonstrated to contribute to tissue damage in experimental models of liver injury and fibrosis. However, less is known about monocyte infiltration in the livers of patients with chronic liver diseases (CLD). In the present study, we demonstrated that CD68+ hepatic macrophages and MAC387+ infiltrating monocytes were significantly increased in the livers of CLD patients with different etiologies as compared with normal liver tissue. In addition, CLD patients with higher inflammatory grading scores had more CD68+ macrophages and MAC387+ monocytes infiltration in their livers compared to those with lower scores. Significantly more MAC387+ infiltrating monocytes were found in the liver tissue of CLD patients with higher fibrotic staging scores compared to those with lower scores. Monocyte chemoattractant protein-1 (MCP-1) expression was significantly increased in the livers of CLD patients with different etiologies. MCP-1 staining scores were significantly positively associated with the numbers of MAC387+ infiltrating monocytes in CLD patients. Taken together, our results demonstrate that infiltrating monocytes may play a pathological role in exacerbating chronic liver inflammation and fibrosis in CLD. MCP-1 may be involved in the monocyte infiltration and progression of liver inflammation and fibrosis in CLD.

RTS,S vaccination is associated with serologic evidence of decreased exposure to Plasmodium falciparum liver- and blood-stage parasites.

PubMed

Campo, Joe J; Aponte, John J; Skinner, Jeff; Nakajima, Rie; Molina, Douglas M; Liang, Li; Sacarlal, Jahit; Alonso, Pedro L; Crompton, Peter D; Felgner, Philip L; Dobaño, Carlota

2015-03-01

The leading malaria vaccine candidate, RTS,S, targets the sporozoite and liver stages of the Plasmodium falciparum life cycle, yet it provides partial protection against disease associated with the subsequent blood stage of infection. Antibodies against the vaccine target, the circumsporozoite protein, have not shown sufficient correlation with risk of clinical malaria to serve as a surrogate for protection. The mechanism by which a vaccine that targets the asymptomatic sporozoite and liver stages protects against disease caused by blood-stage parasites remains unclear. We hypothesized that vaccination with RTS,S protects from blood-stage disease by reducing the number of parasites emerging from the liver, leading to prolonged exposure to subclinical levels of blood-stage parasites that go undetected and untreated, which in turn boosts pre-existing antibody-mediated blood-stage immunity. To test this hypothesis, we compared antibody responses to 824 P. falciparum antigens by protein array in Mozambican children 6 months after receiving a full course of RTS,S (n = 291) versus comparator vaccine (n = 297) in a Phase IIb trial. Moreover, we used a nested case-control design to compare antibody responses of children who did or did not experience febrile malaria. Unexpectedly, we found that the breadth and magnitude of the antibody response to both liver and asexual blood-stage antigens was significantly lower in RTS,S vaccinees, with the exception of only four antigens, including the RTS,S circumsporozoite antigen. Contrary to our initial hypothesis, these findings suggest that RTS,S confers protection against clinical malaria by blocking sporozoite invasion of hepatocytes, thereby reducing exposure to the blood-stage parasites that cause disease. We also found that antibody profiles 6 months after vaccination did not distinguish protected and susceptible children during the subsequent 12-month follow-up period but were strongly associated with exposure. Together

Hepascore and hyaluronic acid as markers of fibrosis in liver disease of mixed aetiology.

PubMed

Costelloe, Seán J; Theocharidou, Eleni; Tsochatzis, Emmanuel; Thalassinos, Evangelos; Martin, Nicholas; Fede, Guiseppe; Thomas, Michael; Burroughs, Anthony K

2015-03-01

To evaluate hyaluronic acid (HA) and Hepascore as diagnostic replacements for liver biopsy in a population with mixed liver disease. The utility of HA concentration and Hepascore for staging fibrosis, detecting any fibrosis and detecting advanced fibrosis, was assessed in 73 consecutive patients, with varied liver pathologies requiring biopsy. Subgroup analyses compared utility of disease-specific and universal cut-offs for HA and Hepascore. Forty-one patients (56.2%) had liver fibrosis on biopsy. HA and Hepascore varied significantly with METAVIR stage, although ranges overlapped, precluding their use in staging fibrosis. When detecting any fibrosis (METAVIR F1-F4), HA and Hepascore had areas under the receiver operator characteristic curve of 0.63 and 0.66, respectively, and approximately two-thirds of patients were correctly categorized using optimal cut-offs. For detection of advanced fibrosis (METAVIR F3/4), HA and Hepascore had areas under the receiver operator characteristic curve of 0.81 and 0.80, respectively, and three-quarters of patients were correctly categorized using optimal cut-offs. In subgroup analysis, locally derived, disease-specific cut-offs in hepatitis C virus patients yielded greatest diagnostic efficiency, whereas the tests performed worst in cryptogenic aetiologies. HA and Hepascore cannot accurately stage hepatic fibrosis in this population. Locally derived, disease-specific cut-offs for HA gave the higher diagnostic efficiency observed. Although HA and Hepascore may be useful where the disease aetiology is known, particularly in established hepatitis C virus, the high cost of false positives and false negatives are such that neither a reliable enough to replace biopsy without substantial further characterization.

Mechanisms and cell signaling in alcoholic liver disease

PubMed Central

Beier, Juliane I.; McClain, Craig J.

2013-01-01

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. The poor prognosis of ALD implies that preventing disease progression would be more effective than treating end-stage liver disease. An obvious avenue of prevention would be to remove the damaging agent; however, the infamously high rate of recidivism in alcoholics makes maintaining abstinence a difficult treatment goal to prevent ALD. Indeed, although the progression of ALD is well-characterized, there is no universally accepted therapy available to halt or reverse this process in humans. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of ALD, rational targeted therapy can be developed to treat or prevent ALD. The purpose of this review is to summarize the established and proposed mechanisms by which chronic alcohol abuse damages the liver and to highlight key signaling events known or hypothesized to mediate these effects. PMID:20868231

Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

PubMed

Basu, P P; Aloysius, M M; Shah, N J; Brown, R S

2014-04-01

Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier. © 2014 John Wiley & Sons Ltd.

Model for end-stage liver disease dynamic stratification of survival benefit.

PubMed

Avolio, A W; Siciliano, M; Barone, M; Lai, Q; Caracciolo, G L; Barbarino, R; Nicolotti, N; Lirosi, M C; Gasbarrini, A; Agnes, S

2012-09-01

Only patients with Model for End-stage Liver Disease (MELD) scores ≥18 or ≥17 experience a survival benefit (SB) at 12 and 36 months after liver transplantation (OLT). The SB calculation estimates the difference after stratification for risk categories between the survival rate of transplanted versus waiting list patients. The aim of this study was to perform a short- and long-term (60 months) SB analyses of a Italian OLT program. One-hundred seventy-one patients were stratified into four MELD classes (6-14, 15-18, 19-25, 26-40), and two groups: namely, waiting list (WL) and transplanted groups (TX). The median waiting time for transplanted patients was 4.4 months (range, 0-35). SB was expressed as mortality hazard ratio (MHR) as obtained through a Cox regression analysis using as a covariate the status of each patient in the waiting list (WL = 0, reference group) or the TX group (TX = 1). Values over 1 indicated the MHR in favor of the WL with the values below 1 indicating MHR in favor of Tx. In the MELD class 6 to 14, the MHR was above 1 at 3 and 6 months, indicating an SB in favor of WL; subsequently, the MHR dropped below 1, indicating an SB in favor of TX (P < .05). In the MELD class 15 to 18 the MHR was above 1 at 3 months, but below 1 subsequently (P < .05). For MELD classes 19 to 25 and 26 to 40, the MHR was always below 1 (P < .01). According to the SB approach, patients in the MELD class 6 to 14 could safely wait for at least 36 months; patients in the MELD class 15 to 18 should likely remain no longer than 12 months on the waiting list, and all the remaining patients with MELD > 18 should be transplanted as soon as possible. OLT should not be precluded but only postponed for MELD < 19 patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Deep learning for staging liver fibrosis on CT: a pilot study.

PubMed

Yasaka, Koichiro; Akai, Hiroyuki; Kunimatsu, Akira; Abe, Osamu; Kiryu, Shigeru

2018-05-14

To investigate whether liver fibrosis can be staged by deep learning techniques based on CT images. This clinical retrospective study, approved by our institutional review board, included 496 CT examinations of 286 patients who underwent dynamic contrast-enhanced CT for evaluations of the liver and for whom histopathological information regarding liver fibrosis stage was available. The 396 portal phase images with age and sex data of patients (F0/F1/F2/F3/F4 = 113/36/56/66/125) were used for training a deep convolutional neural network (DCNN); the data for the other 100 (F0/F1/F2/F3/F4 = 29/9/14/16/32) were utilised for testing the trained network, with the histopathological fibrosis stage used as reference. To improve robustness, additional images for training data were generated by rotating or parallel shifting the images, or adding Gaussian noise. Supervised training was used to minimise the difference between the liver fibrosis stage and the fibrosis score obtained from deep learning based on CT images (F DLCT score) output by the model. Testing data were input into the trained DCNNs to evaluate their performance. The F DLCT scores showed a significant correlation with liver fibrosis stage (Spearman's correlation coefficient = 0.48, p < 0.001). The areas under the receiver operating characteristic curves (with 95% confidence intervals) for diagnosing significant fibrosis (≥ F2), advanced fibrosis (≥ F3) and cirrhosis (F4) by using F DLCT scores were 0.74 (0.64-0.85), 0.76 (0.66-0.85) and 0.73 (0.62-0.84), respectively. Liver fibrosis can be staged by using a deep learning model based on CT images, with moderate performance. • Liver fibrosis can be staged by a deep learning model based on magnified CT images including the liver surface, with moderate performance. • Scores from a trained deep learning model showed moderate correlation with histopathological liver fibrosis staging. • Further improvement are necessary before utilisation in clinical

A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum.

PubMed

Roth, Alison; Maher, Steven P; Conway, Amy J; Ubalee, Ratawan; Chaumeau, Victor; Andolina, Chiara; Kaba, Stephen A; Vantaux, Amélie; Bakowski, Malina A; Luque, Richard Thomson; Adapa, Swamy Rakesh; Singh, Naresh; Barnes, Samantha J; Cooper, Caitlin A; Rouillier, Mélanie; McNamara, Case W; Mikolajczak, Sebastian A; Sather, Noah; Witkowski, Benoît; Campo, Brice; Kappe, Stefan H I; Lanar, David E; Nosten, François; Davidson, Silas; Jiang, Rays H Y; Kyle, Dennis E; Adams, John H

2018-05-09

Malaria liver stages represent an ideal therapeutic target with a bottleneck in parasite load and reduced clinical symptoms; however, current in vitro pre-erythrocytic (PE) models for Plasmodium vivax and P. falciparum lack the efficiency necessary for rapid identification and effective evaluation of new vaccines and drugs, especially targeting late liver-stage development and hypnozoites. Herein we report the development of a 384-well plate culture system using commercially available materials, including cryopreserved primary human hepatocytes. Hepatocyte physiology is maintained for at least 30 days and supports development of P. vivax hypnozoites and complete maturation of P. vivax and P. falciparum schizonts. Our multimodal analysis in antimalarial therapeutic research identifies important PE inhibition mechanisms: immune antibodies against sporozoite surface proteins functionally inhibit liver stage development and ion homeostasis is essential for schizont and hypnozoite viability. This model can be implemented in laboratories in disease-endemic areas to accelerate vaccine and drug discovery research.

The needs and expectations of overseas liver transplant recipients' families in Taiwan: across different transplantation stages.

PubMed

Chen, H-M; Shih, F-Jong; Pan, Y-J; Shih, F J; Wang, S-S

2014-04-01

This study explored the needs and expectations of Taiwanese overseas liver transplant recipients' families (OLTRFs) across three liver transplantation stages. An exploratory qualitative method was applied to a purposive sample of OLTRFs who received guided face-to-face, semi-structured interviews. Data were subjected to content analysis. Nineteen OLTRF members (15 females, 4 males) aged between 29 and 71 years (mean, 55.1 years) for 19 patients who had end-stage liver diseases were interviewed regarding overseas liver transplantation (OLT) across three stages: pre-departure (first stage), stay in mainland China (second stage), and re-entry into Taiwan (third stage). Five types of needs across OLT stages were reported: (a) knowing precise operation schedule in advance (first to second stages); (b) sharing the caring burdens (second to third stages); (c) knowing the updated health status if possible (all stages); (d) obtaining timely psychological support (all stages); and (e) effective communications between health professionals in Taiwan and mainland China to ensure the caring quality (all stages). Furthermore, five expectations were reported: (a) more donor sources (first stage); (b) comprehensive caring strategies for OLT (first stage); (c) a comprehensive consultation system and timely assistance channels for OLT recipients and their families (second to third stages); (d) a legal and accessible therapy process (all stages); and (e) the cooperation with foreign countries and allowed experience sharing for better quality of patient care (all stages). Most ethnic Chinese believe that family is an integrated system; moreover, there is close attachment between OLT recipients and their families. The needs and expectations of the recipients' family across three transplantation stages were first reported in this project. With this knowledge, the health providers of related countries are empowered by a better understanding of the family's needs and expectations of these

Probiotics in Pediatric Liver Disease.

PubMed

Miloh, Tamir

2015-01-01

The gut-liver axis involves complex interaction between the intestinal microbiome and the liver parenchyma. Probiotics are live microorganisms that are used in a variety of diseases. With currently only 2 randomized-controlled studies (one with Lactobacillus GG and the other with VSL #3), data are scarce to support the clinical effect of probiotic use in children with nonalcoholic fatty liver disease. There is evidence that probiotics decrease the risk of necrotizing enterocolitis and thereby reduce the prevalence of total parenteral nutrition-induced chronic liver disease. Probiotics are used with a few reported positive outcomes in patients with cystic fibrosis and familial hypercholesterolemia and may be promising in other liver conditions. Probiotics are generally safe and well tolerated in children, premature infants, and in patients after liver transplantation. Large, prospective, randomized clinical trials are needed to evaluate the benefit of probiotics in children with liver diseases.

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

Nonalcoholic Fatty Liver Disease: Noninvasive Methods of Diagnosing Hepatic Steatosis

PubMed Central

AlShaalan, Rasha; Aljiffry, Murad; Al-Busafi, Said; Metrakos, Peter; Hassanain, Mazen

2015-01-01

Hepatic steatosis is the buildup of lipids within hepatocytes. It is the simplest stage in nonalcoholic fatty liver disease (NAFLD). It occurs in approximately 30% of the general population and as much as 90% of the obese population in the United States. It may progress to nonalcoholic steatohepatitis, which is a state of hepatocellular inflammation and damage in response to the accumulated fat. Liver biopsy remains the gold standard tool to diagnose and stage NAFLD. However, it comes with the risk of complications ranging from simple pain to life-threatening bleeding. It is also associated with sampling error. For these reasons, a variety of noninvasive radiological markers, including ultrasound, computed tomography, magnetic resonance spectroscopy, and the controlled attenuation parameter using transient elastography and Xenon-133 scan have been proposed to increase our ability to diagnose NAFLD, hence avoiding liver biopsy. The aim of this review is to discuss the utility and accuracy of using available noninvasive diagnostic modalities for fatty liver in NAFLD. PMID:25843191

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.

Folate, Alcohol, and Liver Disease

PubMed Central

Medici, Valentina; Halsted, Charles H.

2013-01-01

Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of alcoholic liver disease with particular focus on ethanol-induced alterations in methionine metabolism which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of alcoholic liver disease based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

Plasmodium berghei EXP-1 interacts with host Apolipoprotein H during Plasmodium liver-stage development

PubMed Central

Sá e Cunha, Cláudia; Nyboer, Britta; Heiss, Kirsten; Sanches-Vaz, Margarida; Fontinha, Diana; Wiedtke, Ellen; Grimm, Dirk; Przyborski, Jude Marek; Mota, Maria M.; Prudêncio, Miguel; Mueller, Ann-Kristin

2017-01-01

The first, obligatory replication phase of malaria parasite infections is characterized by rapid expansion and differentiation of single parasites in liver cells, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. Hepatic Plasmodium development occurs inside a specialized membranous compartment termed the parasitophorous vacuole (PV). Here, we show that, during the parasite’s hepatic replication, the C-terminal region of the parasitic PV membrane protein exported protein 1 (EXP-1) binds to host Apolipoprotein H (ApoH) and that this molecular interaction plays a pivotal role for successful Plasmodium liver-stage development. Expression of a truncated EXP-1 protein, missing the specific ApoH interaction site, or down-regulation of ApoH expression in either hepatic cells or mouse livers by RNA interference resulted in impaired intrahepatic development. Furthermore, infection of mice with sporozoites expressing a truncated version of EXP-1 resulted in both a significant reduction of liver burden and delayed blood-stage patency, leading to a disease outcome different from that generally induced by infection with wild-type parasites. This study identifies a host–parasite protein interaction during the hepatic stage of infection by Plasmodium parasites. The identification of such vital interactions may hold potential toward the development of novel malaria prevention strategies. PMID:28137845

Non-invasive assessment of liver fibrosis using two-dimensional shear wave elastography in patients with autoimmune liver diseases.

PubMed

Zeng, Jie; Huang, Ze-Ping; Zheng, Jian; Wu, Tao; Zheng, Rong-Qin

2017-07-14

To determine the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE) for the non-invasive assessment of liver fibrosis in patients with autoimmune liver diseases (AILD) using liver biopsy as the reference standard. Patients with AILD who underwent liver biopsy and 2D-SWE were consecutively enrolled. Receiver operating characteristic (ROC) curves were constructed to assess the overall accuracy and to identify optimal cut-off values. The characteristics of the diagnostic performance were determined for 114 patients with AILD. The areas under the ROC curves for significant fibrosis, severe fibrosis, and cirrhosis were 0.85, 0.85, and 0.86, respectively, and the optimal cut-off values associated with significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 9.7 kPa, 13.2 kPa and 16.3 kPa, respectively. 2D-SWE showed sensitivity values of 81.7% for significant fibrosis, 83.0% for severe fibrosis, and 87.0% for cirrhosis, and the respective specificity values were 81.3%, 74.6%, and 80.2%. The overall concordance rate of the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages was 53.5%. 2D-SWE showed promising diagnostic performance for assessing liver fibrosis stages and exhibited high cut-off values in patients with AILD. Low overall concordance rate was observed in the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages.

Non-invasive assessment of liver fibrosis using two-dimensional shear wave elastography in patients with autoimmune liver diseases

PubMed Central

Zeng, Jie; Huang, Ze-Ping; Zheng, Jian; Wu, Tao; Zheng, Rong-Qin

2017-01-01

AIM To determine the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE) for the non-invasive assessment of liver fibrosis in patients with autoimmune liver diseases (AILD) using liver biopsy as the reference standard. METHODS Patients with AILD who underwent liver biopsy and 2D-SWE were consecutively enrolled. Receiver operating characteristic (ROC) curves were constructed to assess the overall accuracy and to identify optimal cut-off values. RESULTS The characteristics of the diagnostic performance were determined for 114 patients with AILD. The areas under the ROC curves for significant fibrosis, severe fibrosis, and cirrhosis were 0.85, 0.85, and 0.86, respectively, and the optimal cut-off values associated with significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 9.7 kPa, 13.2 kPa and 16.3 kPa, respectively. 2D-SWE showed sensitivity values of 81.7% for significant fibrosis, 83.0% for severe fibrosis, and 87.0% for cirrhosis, and the respective specificity values were 81.3%, 74.6%, and 80.2%. The overall concordance rate of the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages was 53.5%. CONCLUSION 2D-SWE showed promising diagnostic performance for assessing liver fibrosis stages and exhibited high cut-off values in patients with AILD. Low overall concordance rate was observed in the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages. PMID:28765706

Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease

PubMed Central

Kawanaka, Miwa; Nishino, Ken; Oka, Takahito; Urata, Noriyo; Nakamura, Jun; Suehiro, Mitsuhiko; Kawamoto, Hirofumi; Chiba, Yasutaka; Yamada, Gotaro

2015-01-01

Objective Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH). Methods In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA), tyrosine (Tyr), and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index), biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin), and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid). Results Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels increased with increasing fibrotic stage. These results suggest that amino acid imbalance and insulin resistance are intimately involved in a complex pathogenic mechanism for NASH. PMID:26082668

Hepatitis B virus pre-S/S variants in liver diseases.

PubMed

Chen, Bing-Fang

2018-04-14

Chronic hepatitis B is a global health problem. The clinical outcomes of chronic hepatitis B infection include asymptomatic carrier state, chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Because of the spontaneous error rate inherent to viral reverse transcriptase, the hepatitis B virus (HBV) genome evolves during the course of infection under the antiviral pressure of host immunity. The clinical significance of pre-S/S variants has become increasingly recognized in patients with chronic HBV infection. Pre-S/S variants are often identified in hepatitis B carriers with CH, LC, and HCC, which suggests that these naturally occurring pre-S/S variants may contribute to the development of progressive liver damage and hepatocarcinogenesis. This paper reviews the function of the pre-S/S region along with recent findings related to the role of pre-S/S variants in liver diseases. According to the mutation type, five pre-S/S variants have been identified: pre-S deletion, pre-S point mutation, pre-S1 splice variant, C-terminus S point mutation, and pre-S/S nonsense mutation. Their associations with HBV genotype and the possible pathogenesis of pre-S/S variants are discussed. Different pre-S/S variants cause liver diseases through different mechanisms. Most cause the intracellular retention of HBV envelope proteins and induction of endoplasmic reticulum stress, which results in liver diseases. Pre-S/S variants should be routinely determined in HBV carriers to help identify individuals who may be at a high risk of less favorable liver disease progression. Additional investigations are required to explore the molecular mechanisms of the pre-S/S variants involved in the pathogenesis of each stage of liver disease.

New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases.

PubMed

Ji, Cheng

2014-01-01

Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also  in vivo  in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.

[Hepatic cell transplantation: a new therapy in liver diseases].

PubMed

Pareja, Eugenia; Cortés, Miriam; Martínez, Amparo; Vila, Juan José; López, Rafael; Montalvá, Eva; Calzado, Angeles; Mir, José

2010-07-01

Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.

Histopathology of type C liver disease for determining hepatocellular carcinoma risk factors.

PubMed

Matsumura, Hiroshi; Nirei, Kazushige; Nakamura, Hitomi; Higuchi, Teruhisa; Arakawa, Yasuo; Ogawa, Masahiro; Tanaka, Naohide; Moriyama, Mitsuhiko

2013-08-14

To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma (HCC). We studied 232 patients, who underwent liver biopsy for type C chronic liver disease between 1992 and 2009, with sustained virological response (SVR) after interferon therapy. The patients were divided into two groups according to the F stage 0 + 1 + 2 group (n = 182) and F3 + 4 group (n = 50). We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0 + 1 + 2 and F3 + 4 groups. Then, the background factors and liver histopathological findings, including the degree of fibrosis, F stage, inflammation, necrosis, bile duct obstruction, fat deposition, and degree of irregular regeneration (IR) of hepatocytes, were correlated with the risk of developing HCC. HCC developed in three of 182 (1.6%) patients in the F0 + 1 + 2 group, and four of 50 (8.0%) in the F3 + 4 group. The cumulative incidence of HCC in the former group was found to be significantly lower than in the F3 + 4 group (log rank test P = 0.0224). The presence of atypical hepatocytes among IR of hepatocytes in the F3 + 4 group resulted in a higher cumulative incidence of HCC, and was significantly correlated with risk of HCC development (RR = 20.748, 95%CI: 1.335-322.5, P = 0.0303). Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.

Intestinal microbiota in liver disease.

PubMed

Haque, Tanvir R; Barritt, A Sidney

2016-02-01

The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation. Copyright © 2016. Published by Elsevier Ltd.

Liver Disease in Mitochondrial Disorders

PubMed Central

Lee, Way S.; Sokol, Ronald J.

2013-01-01

Liver involvement, a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period, may manifest as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. There are usually significant neuromuscular symptoms, multisystem involvement, and lactic acidemia. The liver disease is usually progressive and eventually fatal. Current medical therapy of mitochondrial hepatopathies is largely ineffective, and the prognosis is usually poor. The role of liver transplantation in patients with liver failure remains poorly defined because of the systemic nature of the disease that does not respond to transplantation. Several specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and deletion or rearrangement of mitochondrial DNA) have been identified in recent years. Prospective, longitudinal multicenter studies will be needed to address the gaps in our knowledge in these rare liver diseases. PMID:17682973

Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

2015-01-01

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.

Complete Plasmodium falciparum liver-stage development in liver-chimeric mice.

PubMed

Vaughan, Ashley M; Mikolajczak, Sebastian A; Wilson, Elizabeth M; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H I

2012-10-01

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase-deficient mouse (Fah-/-, Rag2-/-, Il2rg-/-, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS-to-blood-stage transition of a human malaria parasite.

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

PubMed

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

2013-10-01

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

Ursodeoxycholic acid for cystic fibrosis-related liver disease.

PubMed

Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L

2014-12-15

Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies.Date of the most recent search of the Group's trials register: 29 May 2014. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. Ten trials have been identified, of which three trials involving 118 participants were included; the dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30 participants from two trials. Improvement in biliary excretion was reported in only one trial and no significant change after treatment was shown. There were no data available for analysis for long-term outcomes such as death or need for liver transplantation. There are few

Living Donor Liver Transplantation for Wilson’s Disease Associated with Fulminant Hepatic Failure: A Case Report

PubMed Central

Huang, Yu; Takatsuki, Mitsuhisa; Soyama, Akihiko; Hidaka, Masaaki; Ono, Shinichiro; Adachi, Tomohiko; Hara, Takanobu; Okada, Satomi; Hamada, Takashi; Eguchi, Susumu

2018-01-01

Patient: Female, 17 Final Diagnosis: Fulminant Wilson’s disease Symptoms: General jaundice • malaise • abdominal pain Medication: — Clinical Procedure: ICU Specialty: Transplantology Objective: Rare disease Background: Liver transplantation is indicated for patients with Wilson’s disease (WD) who present either with acute liver failure or with end-stage liver disease and severe hepatic insufficiency as the first sign of disease. However, almost all reported cases have been treated with death donor liver transplantation. Here we report the case of a patient with WD associated with fulminant hepatic failure (WD-FHF) who underwent living donor liver transplantation (LDLT). Case Report: A 17-year-old female was diagnosed with WD-FHF based on high uric copper (10 603 μg/day, normal <100 μg/day), low serum ceruloplasmin (15 mg/dL, normal >20 mg/dL) and Kayser-Fleischer (K-F) corneal ring, and acute liver failure (ALF), acute renal failure (ARF) and grade 2 hepatic encephalopathy (HE). The model for end-stage liver disease (MELD) score was 35. Due to her critical condition, the patient underwent LDLT utilizing a right liver graft from her 44-year-old mother. The right hepatic vein (RHV) and inferior right hepatic vein (iRHV) were reconstructed. She developed severe liver dysfunction due to a crooked hepatic vein caused by compression from the large graft. To straighten the bend, a reoperation was performed. During the operation, we tried to relieve the compressed hepatic vein by adjusting the graft location, but the benefits were limited. We therefore performed stenting in both the RHV and iRHV on postoperative day 9. The patient gradually improved, exhibiting good liver and renal functions, and was finally discharged on postoperative day 114. Conclusions: When WD-FHF deteriorates too rapidly for conservative management, LDLT is an effective therapeutic strategy. PMID:29549236

Interaction between periodontitis and liver diseases

PubMed Central

Han, Pengyu; Sun, Dianxing; Yang, Jie

2016-01-01

Periodontitis is an oral disease that is highly prevalent worldwide, with a prevalence of 30–50% of the population in developed countries, but only ~10% present with severe forms. It is also estimated that periodontitis results in worldwide productivity losses amounting to ~54 billion USD yearly. In addition to the damage it causes to oral health, periodontitis also affects other types of disease. Numerous studies have confirmed the association between periodontitis and systemic diseases, such as diabetes, respiratory disease, osteoporosis and cardiovascular disease. Increasing evidence also indicated that periodontitis may participate in the progression of liver diseases, such as non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma, as well as affecting liver transplantation. However, to the best of our knowledge, there are currently no reviews elaborating upon the possible links between periodontitis and liver diseases. Therefore, the current review summarizes the human trials and animal experiments that have been conducted to investigate the correlation between periodontitis and liver diseases. Furthermore, in the present review, certain mechanisms that have been postulated to be responsible for the role of periodontitis in liver diseases (such as bacteria, pro-inflammatory mediators and oxidative stress) are considered. The aim of the review is to introduce the hypothesis that periodontitis may be important in the progression of liver disease, thus providing dentists and physicians with an improved understanding of this issue. PMID:27588170

Center variation in the use of nonstandardized model for end-stage liver disease exception points.

PubMed

Goldberg, David S; Makar, George; Bittermann, Therese; French, Benjamin

2013-12-01

The Model for End-Stage Liver Disease (MELD) score is an imperfect prognosticator of waitlist dropout, so transplant centers may apply for exception points to increase a waitlist candidate's priority on the waitlist. Exception applications are categorized as recognized exceptional diagnoses (REDs; eg, hepatocellular carcinoma) and non-REDs (eg, cholangitis). Although prior work has demonstrated regional variation in the use of exceptions, no work has examined the between-center variability. We analyzed all new waitlist candidates from February 27, 2002 to June 3, 2011 to explore variations in the use of non-REDs, for which no strict exception criteria exist. There were 58,641 new waitlist candidates, and 4356 (7.4%) applied for a non-RED exception. The number of applications increased steadily over time, as did the approval rates for such applications: from <50% in 2002 to nearly 75% in 2010. When we adjusted for patient factors, there was significant variability (P < 0.001) in the use of non-RED exceptions in 8 of 11 United Network for Organ Sharing (UNOS) regions and in the approval of these exceptions in 6 of 11 UNOS regions. The variability in the use and approval of non-REDs was clinically significant: waitlist candidates with approved exceptions were significantly more likely to undergo transplantation (68.3% versus 53.4%, P < 0.001) and were less likely to be removed for death or clinical deterioration (10.4% versus 16.2%, P < 0.001). Increased median MELD score at transplantation within a donor service area was the only center factor associated with increased odds of applying for exceptions, while no center factors were associated with having non-RED exceptions approved. Further work is needed to identify other sources of variation to ensure the appropriate and equitable use of non-RED exceptions. © 2013 American Association for the Study of Liver Diseases.

In Vivo and In Vitro Characterization of a Plasmodium Liver Stage-Specific Promoter

PubMed Central

Horstmann, Sebastian; Annoura, Takeshi; del Portillo, Hernando A.; Khan, Shahid M.; Heussler, Volker T.

2015-01-01

Little is known about stage-specific gene regulation in Plasmodium parasites, in particular the liver stage of development. We have previously described in the Plasmodium berghei rodent model, a liver stage-specific (lisp2) gene promoter region, in vitro. Using a dual luminescence system, we now confirm the stage specificity of this promoter region also in vivo. Furthermore, by substitution and deletion analyses we have extended our in vitro characterization of important elements within the promoter region. Importantly, the dual luminescence system allows analyzing promoter constructs avoiding mouse-consuming cloning procedures of transgenic parasites. This makes extensive mutation and deletion studies a reasonable approach also in the malaria mouse model. Stage-specific expression constructs and parasite lines are extremely valuable tools for research on Plasmodium liver stage biology. Such reporter lines offer a promising opportunity for assessment of liver stage drugs, characterization of genetically attenuated parasites and liver stage-specific vaccines both in vivo and in vitro, and may be key for the generation of inducible systems. PMID:25874388

Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease.

PubMed

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

2016-06-07

To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0.05]. Certain adipokines may

The Role of Akt in Chronic Liver Disease and Liver Regeneration.

PubMed

Morales-Ruiz, Manuel; Santel, Ansgar; Ribera, Jordi; Jiménez, Wladimiro

2017-02-01

The liver is continuously exposed to diverse insults, which may culminate in pathological processes causing liver disease. An effective therapeutic strategy for chronic liver disease should control the causal factors of the disease and stimulate functional liver regeneration. Preclinical studies have shown that interventions aimed at maintaining Akt activity in a dysfunctional liver meet most of the criteria. Although the central function of Akt is cell survival, other cellular aspects such as glucose uptake, glycogen synthesis, cell-cycle progression, and lipid metabolism have been shown to be prominent functions of Akt in the context of hepatic physiology. In this review, the authors describe the benefits of the Akt signaling pathway, emphasizing its importance in coordinating proper cellular growth and differentiation during liver regeneration, hepatic function, and liver disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Bisphenol A sulfonation is impaired in metabolic and liver disease

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

Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L., E-mail: angela_slitt@uri.edu

Background: Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives: To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods: The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results:more » In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion: Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. - Highlights: • Present study demonstrates that hepatic SULT 1A1/1A3 are primarily sulfonate BPA in mouse and human. • Hepatic BPA sulfonation is profoundly reduced steatosis, diabetes and cirrhosis. • With BPA-S detectable in urine under low or common exposures, these findings are novel and important.« less

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

PubMed Central

Arora, Anil; Sharma, Praveen

2012-01-01

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

Optical spectroscopy for differentiation of liver tissue under distinct stages of fibrosis: an ex vivo study

NASA Astrophysics Data System (ADS)

Fabila, D. A.; Hernández, L. F.; de la Rosa, J.; Stolik, S.; Arroyo-Camarena, U. D.; López-Vancell, M. D.; Escobedo, G.

2013-11-01

Liver fibrosis is the decisive step towards the development of cirrhosis; its early detection affects crucially the diagnosis of liver disease, its prognosis and therapeutic decision making. Nowadays, several techniques are employed to this task. However, they have the limitation in estimating different stages of the pathology. In this paper we present a preliminary study to evaluate if optical spectroscopy can be employed as an auxiliary tool of diagnosis of biopsies of human liver tissue to differentiate the fibrosis stages. Ex vivo fluorescence and diffuse reflectance spectra were acquired from biopsies using a portable fiber-optic system. Empirical discrimination algorithms based on fluorescence intensity ratio at 500 nm and 680 nm as well as diffuse reflectance intensity at 650 nm were developed. Sensitivity and specificity of around 80% and 85% were respectively achieved. The obtained results show that combined use of fluorescence and diffuse reflectance spectroscopy could represent a novel and useful tool in the early evaluation of liver fibrosis.

How predictive quantitative modelling of tissue organisation can inform liver disease pathogenesis.

PubMed

Drasdo, Dirk; Hoehme, Stefan; Hengstler, Jan G

2014-10-01

From the more than 100 liver diseases described, many of those with high incidence rates manifest themselves by histopathological changes, such as hepatitis, alcoholic liver disease, fatty liver disease, fibrosis, and, in its later stages, cirrhosis, hepatocellular carcinoma, primary biliary cirrhosis and other disorders. Studies of disease pathogeneses are largely based on integrating -omics data pooled from cells at different locations with spatial information from stained liver structures in animal models. Even though this has led to significant insights, the complexity of interactions as well as the involvement of processes at many different time and length scales constrains the possibility to condense disease processes in illustrations, schemes and tables. The combination of modern imaging modalities with image processing and analysis, and mathematical models opens up a promising new approach towards a quantitative understanding of pathologies and of disease processes. This strategy is discussed for two examples, ammonia metabolism after drug-induced acute liver damage, and the recovery of liver mass as well as architecture during the subsequent regeneration process. This interdisciplinary approach permits integration of biological mechanisms and models of processes contributing to disease progression at various scales into mathematical models. These can be used to perform in silico simulations to promote unravelling the relation between architecture and function as below illustrated for liver regeneration, and bridging from the in vitro situation and animal models to humans. In the near future novel mechanisms will usually not be directly elucidated by modelling. However, models will falsify hypotheses and guide towards the most informative experimental design. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Antithrombin III is associated with acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support.

PubMed

Hoefer, Judith; Ulmer, Hanno; Kilo, Juliane; Margreiter, Raimund; Grimm, Michael; Mair, Peter; Ruttmann, Elfriede

2017-06-01

There are few data on the role of liver dysfunction in patients with end-stage heart failure supported by mechanical circulatory support. The aim of our study was to investigate predictors for acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support. A consecutive 164 patients with heart failure with New York Heart Association class IV undergoing mechanical circulatory support were investigated for acute liver failure using the King's College criteria. Clinical characteristics of heart failure together with hemodynamic and laboratory values were analyzed by logistic regression. A total of 45 patients (27.4%) with heart failure developed subsequent acute liver failure with a hospital mortality of 88.9%. Duration of heart failure, cause, cardiopulmonary resuscitation, use of vasopressors, central venous pressure, pulmonary capillary wedge pressure, pulmonary pulsatility index, cardiac index, and transaminases were not significantly associated with acute liver failure. Repeated decompensation, atrial fibrillation (P < .001) and the use of inotropes (P = .007), mean arterial (P = .005) and pulmonary pressures (P = .042), cholinesterase, international normalized ratio, bilirubin, lactate, and pH (P < .001) were predictive of acute liver failure in univariate analysis only. In multivariable analysis, decreased antithrombin III was the strongest single measurement indicating acute liver failure (relative risk per %, 0.84; 95% confidence interval, 0.77-0.93; P = .001) and remained an independent predictor when adjustment for the Model for End-Stage Liver Disease score was performed (relative risk per %, 0.89; 95% confidence interval, 0.80-0.99; P = .031). Antithrombin III less than 59.5% was identified as a cutoff value to predict acute liver failure with a corresponding sensitivity of 81% and specificity of 87%. In addition to the Model for End-Stage Liver Disease score, decreased antithrombin III activity tends

Liver Transplant: Nutrition

MedlinePlus

... transplant and liver disease patients. Pre-Transplant Protein Malnutrition -- Many patients with end stage liver disease do ... to lose weight sensibly and slowly, without causing malnutrition (especially protein malnutrition). Losing excess weight decreases the ...

Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation.

PubMed

Sangro, Bruno; Carpanese, Livio; Cianni, Roberto; Golfieri, Rita; Gasparini, Daniele; Ezziddin, Samer; Paprottka, Philipp M; Fiore, Francesco; Van Buskirk, Mark; Bilbao, Jose Ignacio; Ettorre, Giuseppe Maria; Salvatori, Rita; Giampalma, Emanuela; Geatti, Onelio; Wilhelm, Kai; Hoffmann, Ralf Thorsten; Izzo, Francesco; Iñarrairaegui, Mercedes; Maini, Carlo Ludovico; Urigo, Carlo; Cappelli, Alberta; Vit, Alessandro; Ahmadzadehfar, Hojjat; Jakobs, Tobias Franz; Lastoria, Secondo

2011-09-02

A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium-90-labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole-liver (45.2%) or right-lobe (38.5%) infusions. Typically, patients were Child-Pugh class A (82.5%), had underlying cirrhosis (78.5%), and had good Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1; 87.7%), but many had multinodular disease (75.9%) invading both lobes (53.1%) and/or portal vein occlusion (13.5% branch; 9.8% main). Over half had advanced Barcelona Clinic Liver Cancer (BCLC) staging (BCLC C, 56.3%) and one-quarter had intermediate staging (BCLC B, 26.8%). The median overall survival was 12.8 months (95% confidence interval, 10.9-15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6-38.1 months]; BCLC B, 16.9 months [95% CI, 12.8-22.8 months]; BCLC C, 10.0 months [95% CI, 7.7-10.9 months]). Consistent with this finding , survival varied significantly by ECOG status, hepatic function (Child-Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha-fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All-cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively. This analysis provides robust evidence of the survival

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease.

PubMed

Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Molecular and functional characterization of CD133+ stem/progenitor cells infused in patients with end-stage liver disease reveals their interplay with stromal liver cells.

PubMed

Catani, Lucia; Sollazzo, Daria; Bianchi, Elisa; Ciciarello, Marilena; Antoniani, Chiara; Foscoli, Licia; Caraceni, Paolo; Giannone, Ferdinando Antonino; Baldassarre, Maurizio; Giordano, Rosaria; Montemurro, Tiziana; Montelatici, Elisa; D'Errico, Antonia; Andreone, Pietro; Giudice, Valeria; Curti, Antonio; Manfredini, Rossella; Lemoli, Roberto Massimo

2017-12-01

Growing evidence supports the therapeutic potential of bone marrow (BM)-derived stem/progenitor cells for end-stage liver disease (ESLD). We recently demonstrated that CD133 + stem/progenitor cell (SPC) reinfusion in patients with ESLD is feasible and safe and improve, albeit transiently, liver function. However, the mechanism(s) through which BM-derived SPCs may improve liver function are not fully elucidated. Here, we characterized the circulating SPCs compartment of patients with ESLD undergoing CD133 + cell therapy. Next, we set up an in vitro model mimicking SPCs/liver microenvironment interaction by culturing granulocyte colony-stimulating factor (G-CSF)-mobilized CD133 + and LX-2 hepatic stellate cells. We found that patients with ESLD show normal basal levels of circulating hematopoietic and endothelial progenitors with impaired clonogenic ability. After G-CSF treatment, patients with ESLD were capable to mobilize significant numbers of functional multipotent SPCs, and interestingly, this was associated with increased levels of selected cytokines potentially facilitating SPC function. Co-culture experiments showed, at the molecular and functional levels, the bi-directional cross-talk between CD133 + SPCs and human hepatic stellate cells LX-2. Human hepatic stellate cells LX-2 showed reduced activation and fibrotic potential. In turn, hepatic stellate cells enhanced the proliferation and survival of CD133 + SPCs as well as their endothelial and hematopoietic function while promoting an anti-inflammatory profile. We demonstrated that the interaction between CD133 + SPCs from patients with ESLD and hepatic stellate cells induces significant functional changes in both cellular types that may be instrumental for the improvement of liver function in cirrhotic patients undergoing cell therapy. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Left Lobe Auxiliary Liver Transplantation for End-stage Hepatitis B Liver Cirrhosis.

PubMed

Wang, S-F; Chen, X-P; Chen, Z-S; Wei, L; Dong, S-L; Guo, H; Jiang, J-P; Teng, W-H; Huang, Z-Y; Zhang, W-G

2017-06-01

Auxiliary liver transplantation (ALT) for hepatitis B virus (HBV)-related liver cirrhosis previously showed poor results, because the native liver was a significant source of HBV recurrence and the graft could be rapidly destroyed by HBV infection in an immunosuppressive condition. Four patients with HBV-related liver cirrhosis were unable to undergo orthotopic liver transplantation because the only available grafts of left lobe were too small. Under entecavir-based anti-HBV treatment, they underwent ALT in which the recipient left liver was removed and the small left lobe graft was implanted in the corresponding space. The mean graft weight/recipient weight was 0.49% (range, 0.38%-0.55%). One year after transplantation, the graft sizes were increased to 273% and the remnant livers were decreased to 44%. Serum HBV DNA was persistently undetectable. Periodic graft biopsy showed no signs of tissue injury and negative immunostaining for hepatitis B surface antigen and hepatitis B core antigen. After a mean follow-up period of 21 months, all patients live well with normal graft function. Our study suggests that ALT for HBV-related liver cirrhosis is feasible under entecavir-based anti-HBV treatment. Successful application of small left livers in end-stage liver cirrhosis may significantly increase the pool of left liver grafts for adult patients. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Characteristics and outcome of autoimmune liver disease in Asian children.

PubMed

Lee, Way S; Lum, Su H; Lim, Chooi B; Chong, Sze Y; Khoh, Kim M; Ng, Ruey T; Teo, Kai M; Boey, Christopher C M; Pailoor, Jayalakshmi

2015-04-01

Little is known about autoimmune liver disease (AILD) in Asian children. We studied the clinical features and predictors of outcome in childhood AILD in an Asian population. Retrospective review of AILD [autoimmune hepatitis type 1 and 2 (AIH1, AIH2), primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC)] seen at two pediatric liver units in Malaysia. At presentation, 17 (56%) of the 32 children [19 females, 59%; median (range) age 7.7 (1.8-15.5) years] with AILD (AIH1 = 18, AIH2 = 5, PSC = 0, ASC = 9) had liver cirrhosis. At final review [median (range) duration of follow-up 4.8 (0.4-12) years], 24 patients (75%) survived with a native liver. Twenty-one (66%) were in remission; 19 (AIH1 = 11; AIH2 = 4, ASC = 4) were on prednisolone and/or azathioprine, one on cyclosporine and another on mycophenolate mofetil. Three (AIH1 = 3) were in partial remission. Of the two who underwent liver transplantation (LT; 6.5%; both ASC), one died of primary graft failure after LT. Six patients (19%) died without LT (acute liver failure, n = 1; end-stage liver disease, n = 5). The overall survival rate (native liver and survival post-LT) was 78%. A delay in seeking treatment adversely affected the final outcome [survival with native liver vs. LT or death (duration between onset of disease and treatment; median ± standard error) = 2.5 ± 2.9 months vs. 24.0 ± 13.3 months; p = 0.012]. Although remission was achieved in the majority of patients with prednisolone and/or azathioprine therapy, delay in seeking diagnosis and treatment adversely affects the outcome of childhood AILD in Malaysia.

Superior staging of liver tumors with laparoscopy and laparoscopic ultrasound.

PubMed Central

John, T G; Greig, J D; Crosbie, J L; Miles, W F; Garden, O J

1994-01-01

OBJECTIVE. The authors describe the technique of staging laparoscopy with laparoscopic contact ultrasonography in the preoperative assessment of patients with liver tumors, and assess its impact on the selection of patients for hepatic resection with curative intent. SUMMARY BACKGROUND DATA. Laparoscopy may be useful in the selection of patients with a variety of intra-abdominal malignancies for operative intervention. Laparoscopic ultrasonography is a new technique that combines the principles of high resolution intraoperative contact ultrasound with those of the laparoscopic examination, and thus, allows the laparoscopist to perform detailed assessment of the liver. METHODS. This study analyzes a cohort of 50 consecutive patients who were diagnosed as having potentially resectable liver tumors, and in whom staging laparoscopy was successfully undertaken. Laparoscopic ultrasonography was performed in 43 patients, and the impact of the ensuing findings on the decision to proceed to operative assessment of resectability is examined. The resectability rate in those patients assessed laparoscopically and subsequently submitted to laparotomy is compared with a preceding group of patients in whom no laparoscopic assessment was performed. RESULTS. Laparoscopy demonstrated factors precluding curative resection in 23 patients (46%). Laparoscopic ultrasonography identified liver tumors not visible during laparoscopy in 14 patients (33%), and provided staging information in addition to that derived from laparoscopy alone in 18/43 patients (42%). The resectability rate was significantly higher among those patients undergoing laparoscopic staging (93%) compared with those in whom operative assessment was undertaken without laparoscopy (58%). CONCLUSIONS. Staging laparoscopy with laparoscopic ultrasonography optimizes patient selection for liver resection with curative intent. Images Figure 1. Figure 2. PMID:7986136

A microscale human liver platform that supports the hepatic stages of Plasmodium falciparum and vivax

PubMed Central

March, Sandra; Ng, Shengyong; Velmurugan, Soundarapandian; Galstian, Ani; Shan, Jing; Logan, David; Carpenter, Anne; Thomas, David; Lee Sim, B. Kim; Mota, Maria M.; Hoffman, Stephen L.; Bhatia, Sangeeta N.

2013-01-01

SUMMARY The Plasmodium liver stage is an attractive target for the development of anti-malarial drugs and vaccines, as it provides an opportunity to interrupt the life cycle of the parasite at a critical early stage. However, targeting the liver stage has been difficult. Undoubtedly, a major barrier has been the lack of robust, reliable and reproducible in vitro liver stage cultures. Here, we establish the liver stages for both Plasmodium falciparum and Plasmodium vivax in a microscale human liver platform composed of cryopreserved, micropatterned human primary hepatocytes surrounded by supportive stromal cells. Using this system, we have successfully recapitulated the full liver stage of P. falciparum including the release of infected merozoites and infection of overlaid erythrocytes, and also the establishment of small forms in late liver stages of P. vivax. Finally, we validate the potential of this platform as a tool for medium-throughput anti-malarial drug screening and vaccine development. PMID:23870318

Anesthesia for Patients With Liver Disease

PubMed Central

Rahimzadeh, Poupak; Safari, Saeid; Faiz, Seyed Hamid Reza; Alavian, Seyed Moayed

2014-01-01

Context: Liver plays an important role in metabolism and physiological homeostasis in the body. This organ is unique in its structure and physiology. So it is necessary for an anesthesiologist to be familiar with various hepatic pathophysiologic conditions and consequences of liver dysfunction. Evidence Acquisition: We searched MEDLINE (Pub Med, OVID, MD Consult), SCOPUS and the Cochrane database for the following keywords: liver disease, anesthesia and liver disease, regional anesthesia in liver disease, epidural anesthesia in liver disease and spinal anesthesia in liver disease, for the period of 1966 to 2013. Results: Although different anesthetic regimens are available in modern anesthesia world, but anesthetizing the patients with liver disease is still really tough. Spinal or epidural anesthetic effects on hepatic blood flow and function is not clearly investigated, considering both the anesthetic drug-induced changes and outcomes. Regional anesthesia might be used in patients with advanced liver disease. In these cases lower drug dosages are used, considering the fact that locally administered drugs have less systemic effects. In case of general anesthesia it seems that using inhalation agents (Isoflurane, Desflurane or Sevoflurane), alone or in combination with small doses of fentanyl can be considered as a reasonable regimen. When administering drugs, anesthetist must realize and consider the substantially changed pharmacokinetics of some other anesthetic drugs. Conclusions: Despite the fact that anesthesia in chronic liver disease is a scary and pretty challenging condition for every anesthesiologist, this hazard could be diminished by meticulous attention on optimizing the patient’s condition preoperatively and choosing appropriate anesthetic regimen and drugs in this setting. Although there are paucity of statistics and investigations in this specific group of patients but these little data show that with careful monitoring and considering the above

Complete Plasmodium falciparum liver-stage development in liver-chimeric mice

PubMed Central

Vaughan, Ashley M.; Mikolajczak, Sebastian A.; Wilson, Elizabeth M.; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H.I.

2012-01-01

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase–deficient mouse (Fah–/–, Rag2–/–, Il2rg–/–, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS–to–blood-stage transition of a human malaria parasite. PMID:22996664

Liver transplantation for Wilson's disease in pediatric patients: decision making and timing.

PubMed

Narumi, S; Umehara, M; Toyoki, Y; Ishido, K; Kudo, D; Kimura, N; Kobayashi, T; Sugai, M; Hakamada, K

2012-03-01

Transplantation for Wilson's disease occupies 1/3 of the cases for metabolic diseases in Japan. At the end of 2009, 109 transplantations had been performed including three deceased donor cases in the Japanese registry. We herein discuss problems of transplantation for Wilson's disease as well as its indication, timing, and social care. We retrospectively reviewed four fulminant cases and two chronic cases who underwent living donor liver transplantation. There were two boys and two girls. Four adolescents of average age 11.3 years underwent living donor liver transplantation. Duration from onset to transplantation ranged from 10 to 23 days. Average Model for End-stage Liver Disease (MELD) score was 27.8 (range=24-31). All patients were administrated chelates prior to transplantation. MELD, New Wilson's index, Japanese scoring for liver transplantation, and liver atrophy were useful tools for transplantation decision making; however, none of them was an independent decisive tool. Clinical courses after transplantation were almost uneventful. One girl, however, developed an acute rejection episode due to noncompliance at 3 years after transplantation. All patients currently survive without a graft loss. No disease recurrence had been noted even using living related donors. Two adults evaluated for liver transplantation were listed for deceased donor liver transplantation. Both candidates developed cirrhosis despite long-term medical treatment. There were no appropriate living donors for them. There are many problems in transplantation for Wilson's disease. The indications for liver transplantation should be considered individually using some decision-making tools. The safety of the living donor should be paid the most attention. Copyright © 2012 Elsevier Inc. All rights reserved.

Correlation of endothelin-1 concentration and angiotensin-converting enzyme activity with the staging of liver fibrosis.

PubMed

Kardum, Dusko; Fabijanić, Damir; Lukić, Anita; Romić, Zeljko; Petrovecki, Mladen; Bogdanović, Zoran; Jurić, Klara; Urek-Crncević, Marija; Banić, Marko

2012-06-01

Increased serum angiotensin-converting enzyme (SACE) activity and serum concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We investigated a correlation between the different stages of liver fibrosis and SACE activity and serum ET-1 concentration. Seventy patients with pathohistologically established chronic liver disease were divided in three groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak score 0-1, n =20), medium fibrosis (Ishak score 2-5, n=20) and cirrhosis (Ishak score 6, n=30). SACE activity and ET-1 concentration were determined using commercial ELISA kits. SACE activity and ET-1 concentrations were proportional to the severity of disease, the highest being in patients with liver cirrhosis. Maximal increase in SACE activity was found between minimal and medium fibrosis while maximal increase in ET-1 concentration was revealed between medium fibrosis and cirrhosis. The analysis of the Receiver Operating Characteristic (ROC) curve for SACE activity suggested a cut-off value to separate minimal from medium fibrosis at 59.00 U/L (sensitivity 100%, specificity 64.7%). The cut-off value for serum ET-1 concentration to separate medium fibrosis from cirrhosis was 12.4 pg/mL (sensitivity 96.8%, specificity 94.4%). A positive correlation between SACE activity and ET-1 concentration was registered (Spearman's ñ = 0.438, p = 0.004). Both SACE activity and ET-1 concentration were increased in all stages of liver fibrosis. Cut-off points for SACE activity and ET-1 concentration could be a biochemical marker for the progression of fibrosis. Positive correlation between SACE activity and ET-1 concentration might indicate their interaction in the development of liver cirrhosis.

Tuberculosis and liver disease: management issues.

PubMed

Sonika, Ujjwal; Kar, Premashis

2012-01-01

Tuberculosis is one of the most common diseases in India and has attained epidemic proportions. Tuberculosis and liver are related in many ways. Liver disease can occur due to hepatic tuberculosis or the treatment with various anti-tubercular drugs may precipitate hepatic injury or patients with chronic liver disease may develop tuberculosis and pose special management problems. Tuberculosis per se can affect liver in three forms. The most common form is the diffuse hepatic involvement, seen along with pulmonary or miliary tuberculosis. The second is granulomatous hepatitis and the third, much rarer form presents as focal/local tuberculoma or abscess. Tubercular disease of liver occurring along with pulmonary involvement as in disseminated tuberculosis is treated with standard regimen for pulmonary tuberculosis. Granulomatous hepatitis and tubercular liver abscess are treated like any other extra-pulmonary tubercular lesions without any extra risk of hepatotoxicity by anti-tubercular drugs. Treatment of tuberculosis in patients who already have a chronic liver disease poses various clinical challenges. There is an increased risk of drug induced hepatitis in these patients and its implications are potentially more serious in these patients as their hepatic reserve is already depleted. However, hepatotoxic anti-tubercular drugs can be safely used in these patients if the number of drugs used is adjusted appropriately. Thus, the main principle is to closely monitor the patient for signs of worsening liver disease and to reduce the number of hepatotoxic drugs in the anti-tubercular regimen according to the severity of underlying liver disease.

Microbiota-Liver Axis in Hepatic Disease

PubMed Central

Chassaing, Benoit; Etienne-Mesmin, Lucie; Gewirtz, Andrew T.

2014-01-01

Accumulating evidence indicates that the gut microbiota, long appreciated to be a key determinant of intestinal inflammation, is also playing a key role in chronic inflammatory disease of the liver. Such studies have yielded a general central hypothesis whereby microbiota products activate the innate immune system to drive pro-inflammatory gene expression thus promoting chronic inflammatory disease of the liver. This article reviews the background supporting this hypothesis, outlines how it can potentially explain classic and newly emerging epidemiological chronic inflammatory liver disease, and discusses potential therapeutic means to manipulate the microbiota so as to prevent and/or treat liver disease. PMID:23703735

Evaluation of nutritional indicators and body composition in patients with advanced liver disease enrolled for liver transplantation.

PubMed

Vulcano, Daniela Salate Biagioni; Carvalhaes, Maria Antonieta de Barros Leite; Bakonyi Neto, Alexandre

2013-10-01

Malnutrition is prevalent in patients with advanced liver disease (LD) related to multifactorial causes. Fluid retention can underestimate the nutritional status based on anthropometric measures. We evaluated nutritional indicators and body composition (BC) in patients with liver cirrhosis and correlated them with LD severity. Forty three patients with LD enrolled for liver transplantation were evaluated by Anthropometric measures, subjective evaluation (Global Assessment of Nutritional Status - SGA) and biochemical indicators. Single-frequency electrical bioimpedance (SFE-BIA) was used to evaluate body composition (BC). It measured resistance (R), reactance (Xc) and the phase angle (PA). LD severity was estimated by Child-Pugh and Meld criteria (Model for End-Stage Liver Disease). Child-Pugh index between patients was 7.11 ± 1.70 and Meld was 12.23 ± 4.22. Arm Circumference, Arm Muscle Circumference and Arm Muscle Area, SGA, hemoglobin, hematocrit and albumin showed better correlation with disease severity. Xc and PA showed correlation both with Meld and Child-Pugh score when BC were evaluated. PA was depleted in 55.8% of the patients. Diagnosis of malnutrition varied according to the method. Global assessment of nutritional status showed better correlation with disease severity than with objective methods. Single-frequency electrical bioimpedance for body composition analysis in cirrhotic patients must be cautiously used; however, primary vectors seems to be valid and promising in clinical practice.

Flow Cytometry Based Detection and Isolation of Plasmodium falciparum Liver Stages In Vitro.

PubMed

Dumoulin, Peter C; Trop, Stefanie A; Ma, Jinxia; Zhang, Hao; Sherman, Matthew A; Levitskaya, Jelena

2015-01-01

Malaria, the disease caused by Plasmodium parasites, remains a major global health burden. The liver stage of Plasmodium falciparum infection is a leading target for immunological and pharmacological interventions. Therefore, novel approaches providing specific detection and isolation of live P. falciparum exoerythrocytic forms (EEFs) are warranted. Utilizing a recently generated parasite strain expressing green fluorescent protein (GFP) we established a method which, allows for detection and isolation of developing live P. falciparum liver stages by flow cytometry. Using this technique we compared the susceptibility of five immortalized human hepatocyte cell lines and primary hepatocyte cultures from three donors to infection by P. falciparum sporozoites. Here, we show that EEFs can be detected and isolated from in vitro infected cultures of the HC-04 cell line and primary human hepatocytes. We confirmed the presence of developing parasites in sorted live human hepatocytes and characterized their morphology by fluorescence microscopy. Finally, we validated the practical applications of our approach by re-examining the importance of host ligand CD81 for hepatocyte infection by P. falciparum sporozoites in vitro and assessment of the inhibitory activity of anti-sporozoite antibodies. This methodology provides us with the tools to study both, the basic biology of the P. falciparum liver stage and the effects of host-derived factors on the development of P. falciparum EEFs.

Flow Cytometry Based Detection and Isolation of Plasmodium falciparum Liver Stages In Vitro

PubMed Central

Dumoulin, Peter C.; Trop, Stefanie A.; Ma, Jinxia; Zhang, Hao; Sherman, Matthew A.; Levitskaya, Jelena

2015-01-01

Malaria, the disease caused by Plasmodium parasites, remains a major global health burden. The liver stage of Plasmodium falciparum infection is a leading target for immunological and pharmacological interventions. Therefore, novel approaches providing specific detection and isolation of live P. falciparum exoerythrocytic forms (EEFs) are warranted. Utilizing a recently generated parasite strain expressing green fluorescent protein (GFP) we established a method which, allows for detection and isolation of developing live P. falciparum liver stages by flow cytometry. Using this technique we compared the susceptibility of five immortalized human hepatocyte cell lines and primary hepatocyte cultures from three donors to infection by P. falciparum sporozoites. Here, we show that EEFs can be detected and isolated from in vitro infected cultures of the HC-04 cell line and primary human hepatocytes. We confirmed the presence of developing parasites in sorted live human hepatocytes and characterized their morphology by fluorescence microscopy. Finally, we validated the practical applications of our approach by re-examining the importance of host ligand CD81 for hepatocyte infection by P. falciparum sporozoites in vitro and assessment of the inhibitory activity of anti-sporozoite antibodies. This methodology provides us with the tools to study both, the basic biology of the P. falciparum liver stage and the effects of host-derived factors on the development of P. falciparum EEFs. PMID:26070149

The Relationship Between Fatty Liver Disease and Periodontal Disease

DTIC Science & Technology

2017-03-22

Periodontitis is a highly prevalent and destructive chronic disease. Numerous studies support an association between periodontal disease and other...systemic diseases (diabetes, cardiovascular disease, chronic kidney disease, adverse pregnancy outcome, etc.). Non-alcoholic fatty liver disease is a... chronic inflammatory disease that is characterized by accumulation of triglycerides and fat in the liver which may lead to fibrosis and even cirrhosis

The model for the end-stage liver disease and Child-Pugh score in predicting prognosis in patients with liver cirrhosis and esophageal variceal bleeding.

PubMed

Benedeto-Stojanov, Daniela; Nagorni, Aleksandar; Bjelaković, Goran; Stojanov, Dragan; Mladenović, Bojan; Djenić, Nebojsa

2009-09-01

Esophageal variceal bleeding is one of the most frequent and gravest complications of liver cirrhosis, directly life-threatening. By monitoring certain clinical and laboratory hepatocellular insufficiency parameters (Child-Pugh score), it is possible to determine prognosis in patients who are bleeding and evaluate further therapy. Recently, the Model for the End-Stage Liver Disease (MELD) has been proposed as a tool to predict mortality risk in cirrhotic patients. The aim of the study was to evaluate survival prognosis of cirrhotic patients by the MELD and Child-Pugh scores and to analyze the MELD score prognostic value in patients with both liver cirrhosis and variceal bleeding. We retrospectively evaluated the survival rate of a group of 100 cirrhotic patients of a median age of 57 years. The Child-Pugh score was calculated and the MELD score was computed according to the original formula for each patient. We also analysed clinical and laboratory hepatocellular insufficiency parameters in order to examine their connection with a 15-month survival. The MELD values were correlated with the Child-Pugh scores. The Student's t-test was used for statistical analysis. Twenty-two patients died within 15-months followup. Age and gender did not affect survival rate. The Child-Pugh and MELD scores, as well as ascites and encephalopathy significantly differed between the patients who survived and those who died (p < 0.0001). The International Normalized Ratio (INR) values, serum creatinine and bilirubin were significantly higher, and albumin significantly lower in the patients who died (p < 0.0001). The MELD score was significantly higher in the group of patients who died due to esophageal variceal bleeding (p < 0.0001). In cirrhotic patients the MELD score is an excellent survival predictor at least as well as the Child-Pugh score. Increase in the MELD score is associated with decrease in residual liver function. In the group of patients with liver cirrhosis and esophageal

Nuclear Receptor Variants in Liver Disease

PubMed Central

Müllenbach, Roman; Weber, Susanne N.; Lammert, Frank

2012-01-01

This review aims to provide a snapshot of the actual state of knowledge on genetic variants of nuclear receptors (NR) involved in regulating important aspects of liver metabolism. It recapitulates recent evidence for the application of NR in genetic diagnosis of monogenic (“Mendelian”) liver disease and their use in clinical diagnosis. Genetic analysis of multifactorial liver diseases such as viral hepatitis or fatty liver disease identifies key players in disease predisposition and progression. Evidence from these analyses points towards a role of NR polymorphisms in common diseases, linking regulatory networks to complex and variable phenotypes. The new insights into NR variants also offer perspectives and cautionary advice for their use as handles towards diagnosis and treatment. PMID:22523693

Effects of Melatonin on Liver Injuries and Diseases

PubMed Central

Zhang, Jiao-Jiao; Meng, Xiao; Li, Ya; Zhou, Yue; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

2017-01-01

Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver diseases involve a wide range of liver pathologies, including hepatic steatosis, fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocarcinoma. Despite all the studies performed up to now, therapy choices for liver injuries and diseases are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries and diseases remains a priority. Melatonin is a well-known natural antioxidant, and has many bioactivities. There are numerous studies investigating the effects of melatonin on liver injuries and diseases, and melatonin could regulate various molecular pathways, such as inflammation, proliferation, apoptosis, metastasis, and autophagy in different pathophysiological situations. Melatonin could be used for preventing and treating liver injuries and diseases. Herein, we conduct a review summarizing the potential roles of melatonin in liver injuries and diseases, paying special attention to the mechanisms of action. PMID:28333073

Epigenetic Modifications in the Biology of Nonalcoholic Fatty Liver Disease

PubMed Central

Pirola, Carlos J.; Scian, Romina; Gianotti, Tomas Fernández; Dopazo, Hernán; Rohr, Cristian; Martino, Julio San; Castaño, Gustavo O.; Sookoian, Silvia

2015-01-01

Abstract The 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification whose role in the pathogenesis of metabolic-related complex diseases remains unexplored; 5-hmC appears to be prevalent in the mitochondrial genome. The Ten-Eleven-Translocation (TET) family of proteins is responsible for catalyzing the conversion of 5-methylcytosine to 5-hmC. We hypothesized that epigenetic editing by 5-hmC might be a novel mechanism through which nonalcoholic fatty liver disease (NAFLD)-associated molecular traits could be explained. Hence, we performed an observational study to explore global levels of 5-hmC in fresh liver samples of patients with NAFLD and controls (n = 90) using an enzyme-linked-immunosorbent serologic assay and immunohistochemistry. We also screened for genetic variation in TET 1–3 loci by next generation sequencing to explore its contribution to the disease biology. The study was conducted in 2 stages (discovery and replication) and included 476 participants. We observed that the amount of 5-hmC in the liver of both NAFLD patients and controls was relatively low (up to 0.1%); a significant association was found with liver mitochondrial DNA copy number (R = 0.50, P = 0.000382) and PPARGC1A-mRNA levels (R = −0.57, P = 0.04). We did not observe any significant difference in the 5-hmC nuclear immunostaining score between NAFLD patients and controls; nevertheless, we found that patients with NAFLD (0.4 ± 0.5) had significantly lower nonnuclear-5-hmC staining compared with controls (1.8 ± 0.8), means ± standard deviation, P = 0.028. The missense p.Ile1123Met variant (TET1-rs3998860) was significantly associated with serum levels of caspase-generated CK-18 fragment-cell death biomarker in the discovery and replication stage, and the disease severity (odds ratio: 1.47, 95% confidence interval: 1.10–1.97; P = 0.005). The p.Ile1762Val substitution (TET2-rs2454206) was associated with liver PPARGC1A-methylation and

Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys.

PubMed

Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P; Guo, Xiuqing; Kwon, Soonil; Schwimmer, Jeffrey; Molleston, Jean P; Loomba, Rohit; Brunt, Elizabeth M; Chen, Yii-Der Ida; Goodarzi, Mark O; Taylor, Kent D; Yates, Katherine P; Tonascia, James; Rotter, Jerome I

2017-11-01

To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7 -07 ). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9 -07 ). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data

PubMed Central

Saberi, Behnam; Dadabhai, Alia S; Nanavati, Julie; Wang, Lin; Shinohara, Russell T; Mullin, Gerard E

2018-01-01

AIM To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). METHODS Two individual reviewers identified relevant studies using the PubMed, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows: (1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and (2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant. RESULTS A total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference = -0.86, P = 0.08 (-4.17, 2.46)]. A meta-regression evaluation of serum vitamin 25 (OH)D levels across the individual stages (F0-F4) of fibrosis did not show an association for the six included studies. CONCLUSION Low vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD. PMID:29399288

Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data.

PubMed

Saberi, Behnam; Dadabhai, Alia S; Nanavati, Julie; Wang, Lin; Shinohara, Russell T; Mullin, Gerard E

2018-01-27

To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). Two individual reviewers identified relevant studies using the PubMed, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows: (1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and (2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant. A total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference = -0.86, P = 0.08 (-4.17, 2.46)]. A meta-regression evaluation of serum vitamin 25 (OH)D levels across the individual stages (F0-F4) of fibrosis did not show an association for the six included studies. Low vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD.

In silico identification of genetically attenuated vaccine candidate genes for Plasmodium liver stage.

PubMed

Kumar, Hirdesh; Frischknecht, Friedrich; Mair, Gunnar R; Gomes, James

2015-12-01

Genetically attenuated parasites (GAPs) that lack genes essential for the liver stage of the malaria parasite, and therefore cause developmental arrest, have been developed as live vaccines in rodent malaria models and recently been tested in humans. The genes targeted for deletion were often identified by trial and error. Here we present a systematic gene - protein and transcript - expression analyses of several Plasmodium species with the aim to identify candidate genes for the generation of novel GAPs. With a lack of liver stage expression data for human malaria parasites, we used data available for liver stage development of Plasmodium yoelii, a rodent malaria model, to identify proteins expressed in the liver stage but absent from blood stage parasites. An orthology-based search was then employed to identify orthologous proteins in the human malaria parasite Plasmodium falciparum resulting in a total of 310 genes expressed in the liver stage but lacking evidence of protein expression in blood stage parasites. Among these 310 possible GAP candidates, we further studied Plasmodium liver stage proteins by phyletic distribution and functional domain analyses and shortlisted twenty GAP-candidates; these are: fabB/F, fabI, arp, 3 genes encoding subunits of the PDH complex, dnaJ, urm1, rS5, ancp, mcp, arh, gk, lisp2, valS, palm, and four conserved Plasmodium proteins of unknown function. Parasites lacking one or several of these genes might yield new attenuated malaria parasites for experimental vaccination studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Targeting Dysbiosis for the Treatment of Liver Disease.

PubMed

Anand, Gobind; Zarrinpar, Amir; Loomba, Rohit

2016-02-01

The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging

PubMed Central

Gomaa, Asmaa I; Al-Khatib, Alzhraa; Abdel-Razek, Wael; Hashim, Mohammed Saad; Waked, Imam

2015-01-01

AIM: To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival. METHODS: The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed. RESULTS: At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites

Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging.

PubMed

Gomaa, Asmaa I; Al-Khatib, Alzhraa; Abdel-Razek, Wael; Hashim, Mohammed Saad; Waked, Imam

2015-05-14

To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival. The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed. At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites, patients with AFP ≥ 200

Real time shear wave elastography in chronic liver diseases: Accuracy for predicting liver fibrosis, in comparison with serum markers

PubMed Central

Jeong, Jae Yoon; Kim, Tae Yeob; Sohn, Joo Hyun; Kim, Yongsoo; Jeong, Woo Kyoung; Oh, Young-Ha; Yoo, Kyo-Sang

2014-01-01

AIM: To evaluate the correlation between liver stiffness measurement (LSM) by real-time shear wave elastography (SWE) and liver fibrosis stage and the accuracy of LSM for predicting significant and advanced fibrosis, in comparison with serum markers. METHODS: We consecutively analyzed 70 patients with various chronic liver diseases. Liver fibrosis was staged from F0 to F4 according to the Batts and Ludwig scoring system. Significant and advanced fibrosis was defined as stage F ≥ 2 and F ≥ 3, respectively. The accuracy of prediction for fibrosis was analyzed using receiver operating characteristic curves. RESULTS: Seventy patients, 15 were belonged to F0-F1 stage, 20 F2, 13 F3 and 22 F4. LSM was increased with progression of fibrosis stage (F0-F1: 6.77 ± 1.72, F2: 9.98 ± 3.99, F3: 15.80 ± 7.73, and F4: 22.09 ± 10.09, P < 0.001). Diagnostic accuracies of LSM for prediction of F ≥ 2 and F ≥ 3 were 0.915 (95%CI: 0.824-0.968, P < 0.001) and 0.913 (95%CI: 0.821-0.967, P < 0.001), respectively. The cut-off values of LSM for prediction of F ≥ 2 and F ≥ 3 were 8.6 kPa with 78.2% sensitivity and 93.3% specificity and 10.46 kPa with 88.6% sensitivity and 80.0% specificity, respectively. However, there were no significant differences between LSM and serum hyaluronic acid and type IV collagen in diagnostic accuracy. CONCLUSION: SWE showed a significant correlation with the severity of liver fibrosis and was useful and accurate to predict significant and advanced fibrosis, comparable with serum markers. PMID:25320528

Real time shear wave elastography in chronic liver diseases: accuracy for predicting liver fibrosis, in comparison with serum markers.

PubMed

Jeong, Jae Yoon; Kim, Tae Yeob; Sohn, Joo Hyun; Kim, Yongsoo; Jeong, Woo Kyoung; Oh, Young-Ha; Yoo, Kyo-Sang

2014-10-14

To evaluate the correlation between liver stiffness measurement (LSM) by real-time shear wave elastography (SWE) and liver fibrosis stage and the accuracy of LSM for predicting significant and advanced fibrosis, in comparison with serum markers. We consecutively analyzed 70 patients with various chronic liver diseases. Liver fibrosis was staged from F0 to F4 according to the Batts and Ludwig scoring system. Significant and advanced fibrosis was defined as stage F ≥ 2 and F ≥ 3, respectively. The accuracy of prediction for fibrosis was analyzed using receiver operating characteristic curves. Seventy patients, 15 were belonged to F0-F1 stage, 20 F2, 13 F3 and 22 F4. LSM was increased with progression of fibrosis stage (F0-F1: 6.77 ± 1.72, F2: 9.98 ± 3.99, F3: 15.80 ± 7.73, and F4: 22.09 ± 10.09, P < 0.001). Diagnostic accuracies of LSM for prediction of F ≥ 2 and F ≥ 3 were 0.915 (95%CI: 0.824-0.968, P < 0.001) and 0.913 (95%CI: 0.821-0.967, P < 0.001), respectively. The cut-off values of LSM for prediction of F ≥ 2 and F ≥ 3 were 8.6 kPa with 78.2% sensitivity and 93.3% specificity and 10.46 kPa with 88.6% sensitivity and 80.0% specificity, respectively. However, there were no significant differences between LSM and serum hyaluronic acid and type IV collagen in diagnostic accuracy. SWE showed a significant correlation with the severity of liver fibrosis and was useful and accurate to predict significant and advanced fibrosis, comparable with serum markers.

Challenges in transplantation for alcoholic liver disease.

PubMed

Berlakovich, Gabriela A

2014-07-07

Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist's assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient's pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key

Elastography in Chronic Liver Disease: Modalities, Techniques, Limitations, and Future Directions

PubMed Central

Srinivasa Babu, Aparna; Wells, Michael L.; Teytelboym, Oleg M.; Mackey, Justin E.; Miller, Frank H.; Yeh, Benjamin M.; Ehman, Richard L.

2016-01-01

Chronic liver disease has multiple causes, many of which are increasing in prevalence. The final common pathway of chronic liver disease is tissue destruction and attempted regeneration, a pathway that triggers fibrosis and eventual cirrhosis. Assessment of fibrosis is important not only for diagnosis but also for management, prognostic evaluation, and follow-up of patients with chronic liver disease. Although liver biopsy has traditionally been considered the reference standard for assessment of liver fibrosis, noninvasive techniques are the emerging focus in this field. Ultrasound-based elastography and magnetic resonance (MR) elastography are gaining popularity as the modalities of choice for quantifying hepatic fibrosis. These techniques have been proven superior to conventional cross-sectional imaging for evaluation of fibrosis, especially in the precirrhotic stages. Moreover, elastography has added utility in the follow-up of previously diagnosed fibrosis, the assessment of treatment response, evaluation for the presence of portal hypertension (spleen elastography), and evaluation of patients with unexplained portal hypertension. In this article, a brief overview is provided of chronic liver disease and the tools used for its diagnosis. Ultrasound-based elastography and MR elastography are explored in depth, including a brief glimpse into the evolution of elastography. Elastography is based on the principle of measuring tissue response to a known mechanical stimulus. Specific elastographic techniques used to exploit this principle include MR elastography and ultrasonography-based static or quasistatic strain imaging, one-dimensional transient elastography, point shear-wave elastography, and supersonic shear-wave elastography. The advantages, limitations, and pitfalls of each modality are emphasized. ©RSNA, 2016 PMID:27689833

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.

Fibrosis in nonalcoholic fatty liver disease: Noninvasive assessment using computed tomography volumetry.

PubMed

Fujita, Nobuhiro; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Shirabe, Ken; Yoshizumi, Tomoharu; Kotoh, Kazuhiro; Furusyo, Norihiro; Hida, Tomoyuki; Oda, Yoshinao; Fujioka, Taisuke; Honda, Hiroshi

2016-10-28

To evaluate the diagnostic performance of computed tomography (CT) volumetry for discriminating the fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). A total of 38 NAFLD patients were enrolled. On the basis of CT imaging, the volumes of total, left lateral segment (LLS), left medial segment, caudate lobe, and right lobe (RL) of the liver were calculated with a dedicated liver application. The relationship between the volume percentage of each area and fibrosis stage was analyzed using Spearman's rank correlation coefficient. A receiver operating characteristic (ROC) curve analysis was performed to determine the accuracy of CT volumetry for discriminating fibrosis stage. The volume percentages of the caudate lobe and the LLS significantly increased with the fibrosis stage ( r = 0.815, P < 0.001; and r = 0.465, P = 0.003, respectively). Contrarily, the volume percentage of the RL significantly decreased with fibrosis stage ( r = -0.563, P < 0.001). The volume percentage of the caudate lobe had the best diagnostic accuracy for staging fibrosis, and the area under the ROC curve values for discriminating fibrosis stage were as follows: ≥ F1, 0.896; ≥ F2, 0.929; ≥ F3, 0.955; and ≥ F4, 0.923. The best cut-off for advanced fibrosis (F3-F4) was 4.789%, 85.7% sensitivity and 94.1% specificity. The volume percentage of the caudate lobe calculated by CT volumetry is a useful diagnostic parameter for staging fibrosis in NAFLD patients.

Higher Mortality in registrants with sudden model for end-stage liver disease increase: Disadvantaged by the current allocation policy.

PubMed

Massie, Allan B; Luo, Xun; Alejo, Jennifer L; Poon, Anna K; Cameron, Andrew M; Segev, Dorry L

2015-05-01

Liver allocation is based on current Model for End-Stage Liver Disease (MELD) scores, with priority in the case of a tie being given to those waiting the longest with a given MELD score. We hypothesized that this priority might not reflect risk: registrants whose MELD score has recently increased receive lower priority but might have higher wait-list mortality. We studied wait-list and posttransplant mortality in 69,643 adult registrants from 2002 to 2013. By likelihood maximization, we empirically defined a MELD spike as a MELD increase ≥ 30% over the previous 7 days. At any given time, only 0.6% of wait-list patients experienced a spike; however, these patients accounted for 25% of all wait-list deaths. Registrants who reached a given MELD score after a spike had higher wait-list mortality in the ensuing 7 days than those with the same resulting MELD score who did not spike, but they had no difference in posttransplant mortality. The spike-associated wait-list mortality increase was highest for registrants with medium MELD scores: specifically, 2.3-fold higher (spike versus no spike) for a MELD score of 10, 4.0-fold higher for a MELD score of 20, and 2.5-fold higher for a MELD score of 30. A model incorporating the MELD score and spikes predicted wait-list mortality risk much better than a model incorporating only the MELD score. Registrants with a sudden MELD increase have a higher risk of short-term wait-list mortality than is indicated by their current MELD score but have no increased risk of posttransplant mortality; allocation policy should be adjusted accordingly. © 2015 American Association for the Study of Liver Diseases.

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.

Transient elastography for the assessment of chronic liver disease: Ready for the clinic?

PubMed Central

Cobbold, JFL; Morin, S; Taylor-Robinson, SD

2007-01-01

Transient elastography is a recently developed non-invasive technique for the assessment of hepatic fibrosis. The technique has been subject to rigorous evaluation in a number of studies in patients with chronic liver disease of varying aetiology. Transient elastography has been compared with histological assessment of percutaneous liver biopsy, with high sensitivity and specificity for the diagnosis of cirrhosis, and has also been used to assess pre-cirrhotic disease. However, the cut-off values between different histological stages vary substantially in different studies, patient groups and aetiology of liver disease. More recent studies have examined the possible place of transient elastography in clinical practice, including risk stratification for the development of complications of cirrhosis. This review describes the technique of transient elastography and discusses the interpretation of recent studies, emphasizing its applicability in the clinical setting. PMID:17828808

Oily fish, coffee and walnuts: Dietary treatment for nonalcoholic fatty liver disease.

PubMed

Gupta, Vikas; Mah, Xian-Jun; Garcia, Maria Carmela; Antonypillai, Christina; van der Poorten, David

2015-10-07

Rates of non-alcoholic fatty liver disease (NAFLD) are increasing worldwide in tandem with the metabolic syndrome, with the progressive form of disease, non-alcoholic steatohepatitis (NASH) likely to become the most common cause of end stage liver disease in the not too distant future. Lifestyle modification and weight loss remain the main focus of management in NAFLD and NASH, however, there has been growing interest in the benefit of specific foods and dietary components on disease progression, with some foods showing protective properties. This article provides an overview of the foods that show the most promise and their potential benefits in NAFLD/NASH, specifically; oily fish/ fish oil, coffee, nuts, tea, red wine, avocado and olive oil. Furthermore, it summarises results from animal and human trials and highlights potential areas for future research.

Liver disease stage determines whether the immune response stifles or stimulates tumor growth | Center for Cancer Research

Cancer.gov

Researchers at the Center for Cancer Research and colleagues from three cancer research centers in Germany have discovered a mechanism whereby precancerous liver cells, found in individuals with chronic liver disease, can prevent neighboring cells from becoming cancerous but can also speed the growth of cells that have already become cancerous.  Learn more...

[Liver ultrasound: focal lesions and diffuse diseases].

PubMed

Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

2016-01-01

Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Access to Liver Transplantation in Different ABO-Blood Groups and "Exceptions Points" in a Model for End-Stage Liver Disease Allocation System: A Brazilian Single-Center Study.

PubMed

Martino, R B; Waisberg, D R; Dias, A P M; Inoue, V B S; Arantes, R M; Haddad, L B P; Rocha-Santos, V; Pinheiro, R S N; Nacif, L S; D'Albuquerque, L A C

2018-04-01

In the Model for End-Stage Liver Disease (MELD) system, patients with "MELD exceptions" points may have unfair privilege in the competition for liver grafts. Furthermore, organ distribution following identical ABO blood types may also result in unjust organ allocation. The aim of this study was to investigate access to liver transplantation in a tertiary Brazilian center, regarding "MELD exceptions" situations and among ABO-blood groups. A total of 465 adult patients on the liver waitlist from August 2015 to August 2016 were followed up until August 2017. Patients were divided into groups according to ABO-blood type and presence of "exceptions points." No differences in outcomes were observed among ABO-blood groups. However, patients from B and AB blood types spent less time on the list than patients from A and O groups (median, 46, 176, 415, and 401 days, respectively; P = .03). "Exceptions points" were granted for 141 patients (30.1%), hepatocellular carcinoma being the most common reason (52.4%). Patients with "exceptions points" showed higher transplantation rate, lower mortality on the list, and lower delta-MELD than non-exceptions patients (56.7% vs 19.1% [P < .01]; 18.4% vs 38.5% [P < .01], and 2.0 ± 2.6 vs 6.9 ± 7.0 [P < .01], respectively). Patients with refractory ascites had a higher mortality rate than those with other "exceptions" or without (48%). The MELD system provides equal access to liver transplantation among ABO-blood types, despite shorter time on the waitlist for AB and B groups. The current MELD exception system provides advantages for candidates with "exception points," resulting in superior outcomes compared with those without exceptions. Copyright © 2018 Elsevier Inc. All rights reserved.

Nutritional lipid liver disease of grass carp Ctenopharyngodon idullus (C. et V.)

NASA Astrophysics Data System (ADS)

Lin, Ding; Mao, Yongqing; Cai, Fasheng

1990-12-01

The inadequate nutrient content of pellet feeds widely used in recent years in China for grass carp farming led to lipid liver degeneration in the fish. The present studies show that the pathological features of lipid liver disease are anaemia and hepatic ceroidosis. Other clinical features are; the ratio of liver to body weight exceeds 3% and lipid content exceeds 5%. Extreme infiltration of hepaiocytes by lipid results in the following deteriorative effects: swelling of the liver cells, increase of lipid droplets in the cytoplasm and dislocation of the nucleus, loss of cytoplasm staining affinity, and increased activities of GOT and GPT in serum. Lipid liver degeneration of grass carp can be divided into three stages: 1) deposition of liver lipid; 2) lipid infiltration of hepatic parenchyma; 3) atrophy of liver nucleus. The causes of lipid liver degeneration are complicated, but the main cause is assumed to be an imbalance of nutrients in daily feed and the lock of some lipotropic substances.

Interactions Between the Intestinal Microbiome and Liver Diseases

PubMed Central

Schnabl, Bernd; Brenner, David A.

2014-01-01

The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial products in animal models. However, the contribution of the intestinal microbiome to liver disease goes beyond simple translocation of bacterial products that promote hepatic injury and inflammation. Microbial metabolites produced in a dysbiotic intestinal environment and host factors are equally important in the pathogenesis of liver disease. We review how the combination of liver insult and disruptions in intestinal homeostasis contribute to liver disease. PMID:24440671

Significance of oliguria in critically ill patients with chronic liver disease.

PubMed

Amathieu, Roland; Al-Khafaji, Ali; Sileanu, Florentina E; Foldes, Emily; DeSensi, Rebecca; Hilmi, Ibtesam; Kellum, John A

2017-11-01

Clinical guidelines recommend using Kidney Disease Improving Global Outcomes (KDIGO) criteria for the diagnosis and classification of acute kidney injury (AKI) in patients with chronic liver disease (CLD). Concerns have been raised about the use of urine output (UO) criteria in CLD. We examined the significance of oliguria meeting the urine output criteria for AKI (AKI-UO) and examined its association with clinical outcomes in CLD patients. Using an 8-year clinical database from a large university medical center, 3458 patients with CLD were identified. AKI occurred in 2854 (82.5%) patients when they fulfilled any KDIGO criteria. When serum creatinine (SC) and UO criteria were used, 604 patients (17.5%) had no evidence of AKI and had the lowest hospital mortality rate (5%). Using AKI-UO criteria alone, 2103 patients (60.8%) were classified as stage 2-3 AKI. When only SC criteria were applied, 1281 (61%) of those patients with stage 2-3 AKI-UO were misclassified as either no AKI or AKI stage 1. Patients reclassified with AKI according to UO criteria (AKI-UO) had nearly a 3-fold increased rate of hospital mortality compared with patients without any AKI (14.6% versus 5%; P < 0.001) and more than a 50% increased mortality compared with stage 1 AKI-SC (14.6% versus 9%; P < 0.001). Patients with transient oliguria (AKI-UO stage 1) had increased mortality rates compared with patients without oliguria (14.9% versus 6.9%; P < 0.001). CLD patients have a high incidence of AKI. Compared with creatinine criteria alone, incorporating UO into the diagnostic criteria increased the measured incidence of AKI. Stage 2-3 AKI-UO has a high negative impact on hospital mortality. (Hepatology 2017;66:1592-1600). © 2017 by the American Association for the Study of Liver Diseases.

Screening for Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Diseases: A Cohort Study Using Transient Elastography.

PubMed

Saroli Palumbo, Chiara; Restellini, Sophie; Chao, Che-Yung; Aruljothy, Achuthan; Lemieux, Carolyne; Wild, Gary; Afif, Waqqas; Lakatos, Peter L; Bitton, Alain; Cocciolillo, Sila; Ghali, Peter; Bessissow, Talat; Sebastiani, Giada

2018-06-07

Inflammatory bowel disease (IBD) patients may be at risk for nonalcoholic fatty liver disease (NAFLD) due to chronic inflammation, hepatotoxic drugs, and alteration of the gut microbiota. Prospective data using accurate diagnostic methods are lacking. We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography (TE) with associated controlled attenuation parameter (CAP) in IBD patients as part of a routine screening program. NAFLD was defined as CAP ≥248 dB/m. Significant liver fibrosis (stage 2 or higher out of 4) was defined as TE measurement ≥7.0 kPa. Predictors of NAFLD and significant liver fibrosis were determined by logistic regression analysis. A total of 384 patients (mean age 42.4 years, 45.0% male, 64.6% with Crohn's disease) with no significant alcohol intake were included. Prevalence of NAFLD and significant liver fibrosis was 32.8% and 12.2%, respectively. Independent predictors of NAFLD were older age (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.15-1.82), higher body mass index (BMI; aOR, 1.31; 95% CI, 1.20-1.42) and higher triglycerides (aOR, 1.45; 95% CI, 1.01-2.09). Significant liver fibrosis was independently predicted by older age (aOR, 1.38; 95% CI, 1.12-1.64) and higher BMI (aOR, 1.14; 95% CI, 1.07-1.23). Extrahepatic diseases were more common in IBD patients with NAFLD compared with those without, namely chronic kidney disease (10.3 vs 2.3%; P < 0.001) and cardiovascular diseases (11.3 vs 4.7%; P = 0.02). NAFLD diagnosed by TE with CAP is a frequent comorbidity in IBD patients and is associated with extrahepatic diseases. Noninvasive screening strategies could help early diagnosis and initiation of interventions, including weight loss, correction of dyslipidemia, and linkage to care. 10.1093/ibd/izy200_video1izy200.video15794817619001.

Phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease

PubMed Central

Sanchez-Pareja, Andrea; Clément, Sophie; Peyrou, Marion; Spahr, Laurent; Negro, Francesco; Rubbia-Brandt, Laura; Foti, Michelangelo

2016-01-01

AIM: To investigate the protein expression of phosphatase and tensin homolog (PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease. METHODS: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffin-embedded liver sections of patients with non-alcoholic fatty liver disease (NAFLD) (n = 44) or alcoholic liver disease (ALD) (n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients’ clinical history. RESULTS: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis (r = 0.3061, P = 0.0459) and the BMI (r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor (P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients (P < 0.0001). CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN

Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Disease: Is the Liver Another Target?

PubMed Central

Mirrakhimov, Aibek E.; Polotsky, Vsevolod Y.

2012-01-01

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway during sleep leading to intermittent hypoxia (IH). OSA has been associated with all components of the metabolic syndrome as well as with non-alcoholic fatty liver disease (NAFLD). NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to steatohepatitis (NASH), liver fibrosis, and cirrhosis. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Obesity and insulin resistance lead to liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of NAFLD on liver biopsy. However, neither prospective nor interventional studies with continuous positive airway pressure treatment have been performed. Studies in a mouse model showed that IH causes triglyceride accumulation in the liver and liver injury as well as hepatic inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1) IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing free fatty acids (FFA) flux into the liver; (2) IH up-regulates lipid biosynthetic pathways in the liver; (3) IH induces oxidative stress in the liver; (4) IH up-regulates hypoxia inducible factor 1 alpha and possibly HIF-2 alpha, which may increase hepatic steatosis and induce liver inflammation and fibrosis. However, the role of FFA and different transcription factors in the pathogenesis of IH-induced NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done. PMID:23087670

Ursodeoxycholic acid for cystic fibrosis-related liver disease.

PubMed

Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L

2017-09-11

Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. This is an update of a previous review. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies and searched online trial registries.Date of the most recent search of the Group's trials register: 09 April 2017. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. The authors used GRADE to assess the quality of the evidence. Twelve trials have been identified, of which four trials involving 137 participants were included; data were only available from three of the trials (118 participants) since one cross-over trial did not report appropriate data. The dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30

The Use of Induced Pluripotent Stem Cells for the Study and Treatment of Liver Diseases.

PubMed

Hansel, Marc C; Davila, Julio C; Vosough, Massoud; Gramignoli, Roberto; Skvorak, Kristen J; Dorko, Kenneth; Marongiu, Fabio; Blake, William; Strom, Stephen C

2016-02-01

Liver disease is a major global health concern. Liver cirrhosis is one of the leading causes of death in the world and currently the only therapeutic option for end-stage liver disease (e.g., acute liver failure, cirrhosis, chronic hepatitis, cholestatic diseases, metabolic diseases, and malignant neoplasms) is orthotropic liver transplantation. Transplantation of hepatocytes has been proposed and used as an alternative to whole organ transplant to stabilize and prolong the lives of patients in some clinical cases. Although these experimental therapies have demonstrated promising and beneficial results, their routine use remains a challenge due to the shortage of donor livers available for cell isolation, variable quality of those tissues, the potential need for lifelong immunosuppression in the transplant recipient, and high costs. Therefore, new therapeutic strategies and more reliable clinical treatments are urgently needed. Recent and continuous technological advances in the development of stem cells suggest they may be beneficial in this respect. In this review, we summarize the history of stem cell and induced pluripotent stem cell (iPSC) technology in the context of hepatic differentiation and discuss the potential applications the technology may offer for human liver disease modeling and treatment. This includes developing safer drugs and cell-based therapies to improve the outcomes of patients with currently incurable health illnesses. We also review promising advances in other disease areas to highlight how the stem cell technology could be applied to liver diseases in the future. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Endocannabinoids in liver disease and hepatic encephalopathy.

PubMed

Magen, Iddo; Avraham, Yosefa; Berry, Elliot; Mechoulam, Raphael

2008-01-01

Chronic liver disease results from a variety of causes such as hepatitis virus infections, autoimmune processes and alcohol consumption. Its complications include fat deposition, hemodynamic changes and fibrosis. Clinically there may be progression to portal-hypertension and porto-systemic encephalopathy. Pioneering research from the laboratory of Kunos at NIH has stressed the importance of endocannabinoids (ECs) as mediators of some of the pathological processes in chronic liver disease. The present review summarizes the literature on the association between ECs and liver disease, as well as the therapeutic potential of ECs and exogenous cannabinoids in liver disease with emphasis on hepatic encephalopathy.

4(1H)-Quinolones with liver stage activity against Plasmodium berghei.

PubMed

Lacrue, Alexis N; Sáenz, Fabián E; Cross, R Matthew; Udenze, Kenneth O; Monastyrskyi, Andrii; Stein, Steven; Mutka, Tina S; Manetsch, Roman; Kyle, Dennis E

2013-01-01

With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenic Plasmodium berghei parasite (1052Cl1; PbGFP-Luc(con)) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activity in vitro and causal prophylactic activity in vivo. This potent activity makes these compounds ideal candidates for advancement as novel antimalarials.

Early life programming and the risk of non-alcoholic fatty liver disease.

PubMed

Lynch, C; Chan, C S; Drake, A J

2017-06-01

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease and can be considered the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of disease, from the relatively benign simple steatosis to the more serious non-alcoholic steatohepatitis, which can progress to liver cirrhosis, hepatocellular carcinoma and end-stage liver failure, necessitating liver transplantation. Although the increasing prevalence of NAFLD in developed countries has substantial implications for public health, many of the precise mechanisms accounting for the development and progression of NAFLD are unclear. The environment in early life is an important determinant of cardiovascular disease risk in later life and studies suggest this also extends to NAFLD. Here we review data from animal models and human studies which suggest that fetal and early life exposure to maternal under- and overnutrition, excess glucocorticoids and environmental pollutants may confer an increased susceptibility to NAFLD development and progression in offspring and that such effects may be sex-specific. We also consider studies aimed at identifying potential dietary and pharmacological interventions aimed at reducing this risk. We suggest that further human epidemiological studies are needed to ensure that data from animal models are relevant to human health.

Oily fish, coffee and walnuts: Dietary treatment for nonalcoholic fatty liver disease

PubMed Central

Gupta, Vikas; Mah, Xian-Jun; Garcia, Maria Carmela; Antonypillai, Christina; van der Poorten, David

2015-01-01

Rates of non-alcoholic fatty liver disease (NAFLD) are increasing worldwide in tandem with the metabolic syndrome, with the progressive form of disease, non-alcoholic steatohepatitis (NASH) likely to become the most common cause of end stage liver disease in the not too distant future. Lifestyle modification and weight loss remain the main focus of management in NAFLD and NASH, however, there has been growing interest in the benefit of specific foods and dietary components on disease progression, with some foods showing protective properties. This article provides an overview of the foods that show the most promise and their potential benefits in NAFLD/NASH, specifically; oily fish/ fish oil, coffee, nuts, tea, red wine, avocado and olive oil. Furthermore, it summarises results from animal and human trials and highlights potential areas for future research. PMID:26457022

Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests.

PubMed

Kukuk, Guido M; Schaefer, Stephanie G; Fimmers, Rolf; Hadizadeh, Dariusch R; Ezziddin, Samer; Spengler, Ulrich; Schild, Hans H; Willinek, Winfried A

2014-10-01

To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a

Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis.

PubMed

Molloy, Jeffrey W; Calcagno, Christopher J; Williams, Christopher D; Jones, Frances J; Torres, Dawn M; Harrison, Stephen A

2012-02-01

Coffee caffeine consumption (CC) is associated with reduced hepatic fibrosis in patients with chronic liver diseases, such as hepatitis C. The association of CC with nonalcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to correlate CC with the prevalence and severity of NAFLD. Patients involved in a previously published NAFLD prevalence study, as well as additional NASH patients identified in the Brooke Army Medical Center Hepatology clinic, were queried about their caffeine intake. A validated questionnaire for CC was utilized to assess for a relationship between caffeine and four groups: ultrasound negative (controls), bland steatosis/not-NASH, NASH stage 0-1, and NASH stage 2-4. A total of 306 patients responded to the CC questionnaire. Average milligrams of total caffeine/coffee CC per day in controls, bland steatosis/not-NASH, NASH stage 0-1, and NASH stage 2-4 were 307/228, 229/160, 351/255, and 252/152, respectively. When comparing patients with bland steatosis/not-NASH to those with NASH stage 0-1, there was a significant difference in CC between the two groups (P = 0.005). Additionally, when comparing patients with NASH stage 0-1 to those with NASH stage 2-4, there was a significant difference in coffee CC (P = 0.016). Spearman's rank correlation analysis further supported a negative relationship between coffee CC and hepatic fibrosis (r = -0.215; P = 0.035). Coffee CC is associated with a significant reduction in risk of fibrosis among NASH patients. Copyright © 2011 American Association for the Study of Liver Diseases.

Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease.

PubMed

Reilly, Norelle R; Lebwohl, Benjamin; Hultcrantz, Rolf; Green, Peter H R; Ludvigsson, Jonas F

2015-06-01

Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

PubMed

Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

2018-01-01

An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

Bacterial Infections Change Natural History of Cirrhosis Irrespective of Liver Disease Severity.

PubMed

Dionigi, Elena; Garcovich, Matteo; Borzio, Mauro; Leandro, Gioacchino; Majumdar, Avik; Tsami, Aikaterini; Arvaniti, Vasiliki; Roccarina, Davide; Pinzani, Massimo; Burroughs, Andrew K; O'Beirne, James; Tsochatzis, Emmanuel A

2017-04-01

We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of cirrhosis. We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria. We used competing risk analysis and propensity score matching for data analysis. 501 patients (63% male, 48% alcoholic liver disease, median Model of End-stage Liver Disease (MELD)=17) underwent 781 admissions over the study period. Portal hypertensive bleeding and complicated ascites were the commonest reasons of admission. The incidence of proven bacterial infection was 25.6% (60% community acquired and 40% nosocomial). Survival rates at 3, 6, 12, and 30 months were 83%, 77%, 71%, and 62% in patients without diagnosis of infection, vs. 50%, 46%, 41%, and 34% in patients with diagnosis of infection. Overall survival was independently associated with MELD score (hazards ratio (HR) 1.099), intensive care (ITU) stay (HR 1.967) and bacterial infection (HR 2.226). Bacterial infection was an independent predictor of survival even when patients who died within the first 30 days were excluded from the analysis in Cox regression (HR 2.013) and competing risk Cox models in all patients (HR 1.46) and propensity risk score-matched infected and non-infected patients (HR 1.67). Infection most likely represents a distinct prognostic stage of cirrhosis, which affects survival irrespective of disease severity, even after recovery from the infective episode.

Liver Disease in the HIV-Infected Individual

PubMed Central

Price, Jennifer C.; Thio, Chloe L.

2010-01-01

Since the advent of effective antiretroviral therapy (ART) for human immunodeficiency virus-1 (HIV), there has been a substantial decrease in deaths related to acquired immunodeficiency syndrome (AIDS). However, in the ART-era liver disease is now the most common non-AIDS related cause of death among HIV-infected patients, accounting for 14-18% of all deaths in this population and almost half of deaths among hospitalized HIV-infected patients. Just as the burden of non-AIDS morbidity and mortality has changed in the ART-era, the types of liver disease the clinician is likely to encounter among these patients have changed as well. This review will discuss the causes of liver disease in the HIV-infected population in the ART-era, including chronic hepatitis C virus, chronic hepatitis B virus, medication-related hepatotoxicity, alcohol abuse, nonalcoholic fatty liver disease, and AIDS-related liver diseases. PMID:20851211

Validation of Shear Wave Elastography Cutoff Values on the Supersonic Aixplorer for Practical Clinical Use in Liver Fibrosis Staging.

PubMed

Dhyani, Manish; Grajo, Joseph R; Bhan, Atul K; Corey, Kathleen; Chung, Raymond; Samir, Anthony E

2017-06-01

The purpose of this study was to determine the validity of previously established ultrasound shear wave elastography (SWE) cut-off values (≥F2 fibrosis) on an independent cohort of patients with chronic liver disease. In this cross-sectional study, approved by the institutional review board and compliant with the Health Insurance Portability and Accountability Act, 338 patients undergoing liver biopsy underwent SWE using an Aixplorer ultrasound machine (SuperSonic Imagine, Aix-en-Provence, France). Median SWE values were calculated from sets of 10 elastograms. A single blinded pathologist evaluated METAVIR fibrosis staging as the gold standard. The study analyzed 277 patients with a mean age of 48 y. On pathologic examination, 212 patients (76.5%) had F0-F1 fibrosis, whereas 65 (23.5%) had ≥F2 fibrosis. Spearman's correlation of fibrosis with SWE was 0.456 (p < 0.001). A cut-off value of 7.29 kPa yielded sensitivity of 95.4% and specificity of 50.5% for the diagnosis of METAVIR stage ≥F2 liver fibrosis in patients with liver disease using the SuperSonic Imagine Aixplorer SWE system. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Neutrophil gelatinase‐associated lipocalin level is a prognostic factor for survival in rat and human chronic liver diseases

PubMed Central

Yoshikawa, Kyoko; Iwasa, Motoh; Kojima, Shinichi; Yoshizawa, Naohiko; Tempaku, Mina; Sugimoto, Ryosuke; Yamamoto, Norihiko; Sugimoto, Kazushi; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Takei, Yoshiyuki

2017-01-01

Chronic liver disease patients often have complications, such as hepatocellular carcinoma (HCC) and acute bacterial infection. Model for end‐stage liver disease and Child‐Pugh scores are useful prognostic factors for chronic liver diseases but not for all chronic conditions, such as HCC. Our investigative aim targeted the prognostic abilities of neutrophil gelatinase‐associated lipocalin (NGAL) in rat and human chronic liver diseases. Blood NGAL levels were measured by enzyme‐linked immunosorbent assay in rats with cirrhosis and 96 patients with chronic liver disease and HCC. We examined the correlation between blood NGAL levels and liver functions as well as survival. In our rat model, liver NGAL expression was assessed by immunostaining, real‐time quantitative polymerase chain reaction, and immunoblot. In rats with cirrhosis, blood NGAL levels were continuously and significantly elevated in the deceased group and were significantly correlated with liver functions. Liver NGAL, toll‐like receptor 4, and interleukin‐6 levels were increased in the deceased group compared to the survival group. Blood NGAL levels were significantly correlated with liver NGAL levels, indicating blood NGAL was derived from the liver. In patients with chronic liver disease, blood NGAL levels were associated with liver function and renal function. Blood NGAL levels were significantly increased in patients with chronic liver disease with HCC compared to without HCC. For the survival group, 38 out of 96 patients were dead in the average follow‐up period of 9.9 months. The patients with blood NGAL ≤119 ng/mL had significantly longer rates of survival compared to patients with blood NGAL >119 ng/mL. Conclusion: Blood NGAL predicts the survival rate in rat and human chronic liver diseases. Our findings suggest blood NGAL may be prognostic of survival in chronic liver diseases complicated by HCC. (Hepatology Communications 2017;1:946–956) PMID:29404502

Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

PubMed

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases

PubMed Central

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations. PMID:18528476

Childhood Liver Cancer Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

Cancer.gov

Liver cancer is rare in children and adolescents. There are two main types of childhood liver cancer. Hepatoblastoma usually affects children 3 years and younger, and hepatocellular carcinoma occurs in older children and teenagers. Learn about risk factors, tests to diagnose, and stages of childhood liver cancer.

Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging.

PubMed

Ploemen, Ivo H J; Prudêncio, Miguel; Douradinha, Bruno G; Ramesar, Jai; Fonager, Jannik; van Gemert, Geert-Jan; Luty, Adrian J F; Hermsen, Cornelus C; Sauerwein, Robert W; Baptista, Fernanda G; Mota, Maria M; Waters, Andrew P; Que, Ivo; Lowik, Clemens W G M; Khan, Shahid M; Janse, Chris J; Franke-Fayard, Blandine M D

2009-11-18

The quantitative analysis of Plasmodium development in the liver in laboratory animals in cultured cells is hampered by low parasite infection rates and the complicated methods required to monitor intracellular development. As a consequence, this important phase of the parasite's life cycle has been poorly studied compared to blood stages, for example in screening anti-malarial drugs. Here we report the use of a transgenic P. berghei parasite, PbGFP-Luc(con), expressing the bioluminescent reporter protein luciferase to visualize and quantify parasite development in liver cells both in culture and in live mice using real-time luminescence imaging. The reporter-parasite based quantification in cultured hepatocytes by real-time imaging or using a microplate reader correlates very well with established quantitative RT-PCR methods. For the first time the liver stage of Plasmodium is visualized in whole bodies of live mice and we were able to discriminate as few as 1-5 infected hepatocytes per liver in mice using 2D-imaging and to identify individual infected hepatocytes by 3D-imaging. The analysis of liver infections by whole body imaging shows a good correlation with quantitative RT-PCR analysis of extracted livers. The luminescence-based analysis of the effects of various drugs on in vitro hepatocyte infection shows that this method can effectively be used for in vitro screening of compounds targeting Plasmodium liver stages. Furthermore, by analysing the effect of primaquine and tafenoquine in vivo we demonstrate the applicability of real time imaging to assess parasite drug sensitivity in the liver. The simplicity and speed of quantitative analysis of liver-stage development by real-time imaging compared to the PCR methodologies, as well as the possibility to analyse liver development in live mice without surgery, opens up new possibilities for research on Plasmodium liver infections and for validating the effect of drugs and vaccines on the liver stage of

Visualisation and Quantitative Analysis of the Rodent Malaria Liver Stage by Real Time Imaging

PubMed Central

Douradinha, Bruno G.; Ramesar, Jai; Fonager, Jannik; van Gemert, Geert-Jan; Luty, Adrian J. F.; Hermsen, Cornelus C.; Sauerwein, Robert W.; Baptista, Fernanda G.; Mota, Maria M.; Waters, Andrew P.; Que, Ivo; Lowik, Clemens W. G. M.; Khan, Shahid M.; Janse, Chris J.; Franke-Fayard, Blandine M. D.

2009-01-01

The quantitative analysis of Plasmodium development in the liver in laboratory animals in cultured cells is hampered by low parasite infection rates and the complicated methods required to monitor intracellular development. As a consequence, this important phase of the parasite's life cycle has been poorly studied compared to blood stages, for example in screening anti-malarial drugs. Here we report the use of a transgenic P. berghei parasite, PbGFP-Luccon, expressing the bioluminescent reporter protein luciferase to visualize and quantify parasite development in liver cells both in culture and in live mice using real-time luminescence imaging. The reporter-parasite based quantification in cultured hepatocytes by real-time imaging or using a microplate reader correlates very well with established quantitative RT-PCR methods. For the first time the liver stage of Plasmodium is visualized in whole bodies of live mice and we were able to discriminate as few as 1–5 infected hepatocytes per liver in mice using 2D-imaging and to identify individual infected hepatocytes by 3D-imaging. The analysis of liver infections by whole body imaging shows a good correlation with quantitative RT-PCR analysis of extracted livers. The luminescence-based analysis of the effects of various drugs on in vitro hepatocyte infection shows that this method can effectively be used for in vitro screening of compounds targeting Plasmodium liver stages. Furthermore, by analysing the effect of primaquine and tafenoquine in vivo we demonstrate the applicability of real time imaging to assess parasite drug sensitivity in the liver. The simplicity and speed of quantitative analysis of liver-stage development by real-time imaging compared to the PCR methodologies, as well as the possibility to analyse liver development in live mice without surgery, opens up new possibilities for research on Plasmodium liver infections and for validating the effect of drugs and vaccines on the liver stage of

Torins are potent antimalarials that block replenishment of Plasmodium liver stage parasitophorous vacuole membrane proteins

PubMed Central

Hanson, Kirsten K.; Ressurreição, Ana S.; Buchholz, Kathrin; Prudêncio, Miguel; Herman-Ornelas, Jonathan D.; Rebelo, Maria; Beatty, Wandy L.; Wirth, Dyann F.; Hänscheid, Thomas; Moreira, Rui; Marti, Matthias; Mota, Maria M.

2013-01-01

Residence within a customized vacuole is a highly successful strategy used by diverse intracellular microorganisms. The parasitophorous vacuole membrane (PVM) is the critical interface between Plasmodium parasites and their possibly hostile, yet ultimately sustaining, host cell environment. We show that torins, developed as ATP-competitive mammalian target of rapamycin (mTOR) kinase inhibitors, are fast-acting antiplasmodial compounds that unexpectedly target the parasite directly, blocking the dynamic trafficking of the Plasmodium proteins exported protein 1 (EXP1) and upregulated in sporozoites 4 (UIS4) to the liver stage PVM and leading to efficient parasite elimination by the hepatocyte. Torin2 has single-digit, or lower, nanomolar potency in both liver and blood stages of infection in vitro and is likewise effective against both stages in vivo, with a single oral dose sufficient to clear liver stage infection. Parasite elimination and perturbed trafficking of liver stage PVM-resident proteins are both specific aspects of torin-mediated Plasmodium liver stage inhibition, indicating that torins have a distinct mode of action compared with currently used antimalarials. PMID:23836641

Burden of Gastrointestinal and Liver Diseases in Iran: Estimates Based on the Global Burden of Disease, Injuries, and Risk Factors Study, 2010.

PubMed

Malekzadeh, Fatemeh; Sepanlou, Sadaf Ghajarieh; Poustchi, Hossein; Naghavi, Mohsen; Forouzanfar, Mohammad Hossein; Shahraz, Saeid; Moradi-Lakeh, Maziar; Malekzadeh, Reza

2015-07-01

BACKGROUND Gastrointestinal and liver diseases (GILD) constitute a noteworthy portion of causes of death and disability in Iran. However, data on their prevalence and burden is sparse in Iran. The Global Burden of Disease (GBD) study in 2010 has provided invaluable comprehensive data on the burden of GILD in Iran. METHODS Estimations of death, years of life lost due to premature death (YLL), years of life lost due to disability (YLD), disability-adjusted life years (DALY), life expectancy, and healthy life expectancy have been reported for 291 diseases, 67 risk factors, 1160 sequelae, for both sexes and 19 age groups, form 1990 to 2010 for 187 countries. In the current paper, 5 major categories of gastrointestinal (GI) and liver diseases have been investigated as follows: GI infectious diseases, GI and liver cancers, liver infections, chronic end stage liver disease, and other digestive diseases. RESULTS Among women, 7.6% of all deaths and 3.9% of all DALYs were due to digestive and liver diseases in 2010. The respective figures in men were 7.8% of deaths and 4.6% of DALYs. The most important cause of death among children under 5 is diarrhea. Among adults between 15 to 49 years old, the main causes of death are GI and liver cancers and cirrhosis, while diarrhea still remains a major cause of DALY. Among adults 50 years and above, GI and liver cancers and cirrhosis are the main causes of both deaths and DALYs. Gastritis and duodenitis, diarrheal diseases, gall bladder and bile duct diseases, acute hepatitis A, peptic ulcer disease, appendicitis, and acute hepatitis A mainly cause disability rather than death. CONCLUSION GBD study provides invaluable source of data on burden of GILD in Iran. However, there exist limitations, namely overestimation of burden of liver cancer and underestimation of the burden of GI diseases that are usually diagnosed in outpatient settings. The collaboration of scientists across the world and specifically those from developing countries

Steatosis induced CCL5 contributes to early-stage liver fibrosis in nonalcoholic fatty liver disease progress.

PubMed

Li, Bing-Hang; He, Fang-Ping; Yang, Xin; Chen, Yuan-Wen; Fan, Jian-Gao

2017-02-01

The rapidly increasing prevalence of nonalcoholic fatty liver disease (NAFLD) has become one of the major public health threats in China and worldwide. However, during the development of NAFLD, the key mechanism underlying the progression of related fibrosis remains unclear, which greatly impedes the development of optimal NAFLD therapy. In the current study, we were endeavored to characterize a proinflammatory cytokine, CCL5, as a major contributor for fibrosis in NAFLD. The results showed that CCL5 was highly expressed in fatty liver and NASH patients. In NAFLD rats induced by 8-week-HFD, CCL5 and its receptor, CCR5, were significantly up-regulated and liver fibrosis exclusively occurred in this group. In addition, we showed that hepatocytes are the major source contributing to this CCL5 elevation. Interestingly, a CCL5 inhibitor Met-CCL5, significantly decreased liver fibrosis but not hepatic steatosis. Using a cell model of hepatic steatosis, we found that the conditioned medium of lipid-overloaded hepatocytes (Fa2N-4 cells) which produced excessive CCL5 stimulated the profibrotic activities of hepatic stellate cells (LX-2) as manifested by increased migration rate, proliferation and collagen production of LX-2 cells. CCL5 knockdown in Fa2N-4 cells, Met-CCL5 or CCR5 antibody treatment on LX-2 cells all significantly inhibited the conditioned medium of FFA-treated Fa2N-4 cells to exert stimulatory effects on LX-2 cells. Consistently, the conditioned medium of Fa2N-4 cells with CCL5 over-expression significantly enhanced migration rate, cell proliferation and collagen production of LX-2 cells. All these results support that CCL5 produced by steatotic hepatocytes plays an essential role in fibrotic signaling machinery of NAFLD. In addition, we were able to identify C/EBP-β as the up-stream regulator of CCL5 gene transcription in hepatocytes treated with free fatty acid (FFA). Our data strongly supported that CCL5 plays a pivotal regulatory role in

Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease.

PubMed

Bamias, Giorgos; Gizis, Michalis; Delladetsima, Ioanna; Laoudi, Eyfrosyni; Siakavellas, Spyros I; Koutsounas, Ioannis; Kaltsa, Garyfallia; Vlachogiannakos, John; Vafiadis-Zouboulis, Irene; Daikos, George L; Papatheodoridis, George V; Ladas, Spiros D

2016-01-01

Background. Decoy-receptor 3 (DcR3) exerts antiapoptotic and immunomodulatory function and is overexpressed in neoplastic and inflammatory conditions. Serum DcR3 (sDcR3) levels during the chronic hepatitis/cirrhosis/hepatocellular carcinoma (HCC) sequence have not been explored. Objective. To assess the levels and significance of sDcR3 protein in various stages of chronic liver disease. Methods. We compared sDcR3 levels between healthy controls and patients with chronic viral hepatitis (CVH), decompensated cirrhosis (DC), and HCC. Correlations between sDcR3 levels and various patient- and disease-related factors were analyzed. Results. sDcR3 levels were significantly higher in patients with CVH than in controls (P < 0.01). sDcR3 levels were elevated in DC and HCC, being significantly higher compared not only to controls (P < 0.001 for both) but to CVH patients as well (P < 0.001 for both). In addition, DcR3 protein was detected in large quantities in the ascitic fluid of cirrhotics. In patients with CVH, sDcR3 significantly correlated to fibrosis severity, as estimated by Ishak score (P = 0.019) or by liver stiffness measured with elastography (Spearman r = 0.698, P < 0.001). In cirrhotic patients, significant positive correlations were observed between sDcR3 levels and markers of severity of hepatic impairment, including MELD score (r = 0.653, P < 0.001). Conclusions. Circulating levels of DcR3 are elevated during chronic liver disease and correlate with severity of liver damage. sDcR3 may serve as marker for liver fibrosis severity and progression to end-stage liver disease.

Focus on emerging drugs for the treatment of patients with non-alcoholic fatty liver disease

PubMed Central

Federico, Alessandro; Zulli, Claudio; de Sio, Ilario; Del Prete, Anna; Dallio, Marcello; Masarone, Mario; Loguercio, Carmela

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in Western countries and is increasingly being recognized in developing nations. Fatty liver disease encompasses a spectrum of hepatic pathology, ranging from simple steatosis to non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and end-stage liver disease. Moreover, NAFLD is often associated with other metabolic conditions, such as diabetes mellitus type 2, dyslipidemia and visceral obesity. The most recent guidelines suggest the management and treatment of patients with NAFLD considering both the liver disease and the associated metabolic co-morbidities. Diet and physical exercise are considered the first line of treatment for patients with NAFLD, but their results on therapeutic efficacy are often contrasting. Behavior therapy is necessary most of the time to achieve a sufficient result. Pharmacological therapy includes a wide variety of classes of molecules with different therapeutic targets and, often, little evidence supporting the real efficacy. Despite the abundance of clinical trials, NAFLD therapy remains a challenge for the scientific community, and there are no licensed therapies for NAFLD. Urgently, new pharmacological approaches are needed. Here, we will focus on the challenges facing actual therapeutic strategies and the most recent investigated molecules. PMID:25492998

Non-Alcoholic Fatty Liver Disease in HIV Infection.

PubMed

Macías, Juan; Pineda, Juan A; Real, Luis M

2017-01-01

Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population.

Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

PubMed

Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

2018-02-09

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

Liver Biopsy in Chronic Liver Diseases: Is There a Favorable Benefit: Risk Balance?

PubMed

Larrey, Dominique; Meunier, Lucy; Ursic-Bedoya, José

2017-01-01

Liver biopsy is still useful in selected clinical situations in which it is the only tool to obtain information necessary for the diagnosis, the prognosis, and the decision for treatment. Main examples are viral hepatitis with confounding co-morbidities, non alcoholic fatty liver disease, and autoimmune liver diseases.

Single-Pass Percutaneous Liver Biopsy for Diffuse Liver Disease Using an Automated Device: Experience in 154 Procedures

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

Rivera-Sanfeliz, Gerant, E-mail: gerantrivera@ucsd.edu; Kinney, Thomas B.; Rose, Steven C.

2005-06-15

Purpose: To describe our experience with ultrasound (US)-guided percutaneous liver biopsies using the INRAD 18G Express core needle biopsy system.Methods: One hundred and fifty-four consecutive percutaneous core liver biopsy procedures were performed in 153 men in a single institution over 37 months. The medical charts, pathology reports, and radiology files were retrospectively reviewed. The number of needle passes, type of guidance, change in hematocrit level, and adequacy of specimens for histologic analysis were evaluated.Results: All biopsies were performed for histologic staging of chronic liver diseases. The majority of patients had hepatitis C (134/153, 90.2%). All patients were discharged to homemore » after 4 hr of postprocedural observation. In 145 of 154 (94%) biopsies, a single needle pass was sufficient for diagnosis. US guidance was utilized in all but one of the procedures (153/154, 99.4%). The mean hematocrit decrease was 1.2% (44.1-42.9%). Pain requiring narcotic analgesia, the most frequent complication, occurred in 28 of 154 procedures (18.2%). No major complications occurred. The specimens were diagnostic in 152 of 154 procedures (98.7%).Conclusions: Single-pass percutaneous US-guided liver biopsy with the INRAD 18G Express core needle biopsy system is safe and provides definitive pathologic diagnosis of chronic liver disease. It can be performed on an outpatient basis. Routine post-biopsy monitoring of hematocrit level in stable, asymptomatic patients is probably not warranted.« less

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.

Liver Disease and Pulmonary Hypertension

MedlinePlus

... Liver disease can cause what is known as “portal hypertension,” meaning increased blood pressure in the veins that ... diagnosed? A specialist can diagnose POPH by identifying portal hypertension (high pressure in the veins of the liver), ...

PNPLA3 gene in liver diseases.

PubMed

Trépo, Eric; Romeo, Stefano; Zucman-Rossi, Jessica; Nahon, Pierre

2016-08-01

Genome-wide association studies (GWAS) in the field of liver diseases have revealed previously unknown pathogenic loci and generated new biological hypotheses. In 2008, a GWAS performed in a population-based sample study, where hepatic liver fat content was measured by magnetic spectroscopy, showed a strong association between a variant (rs738409 C>G p.I148M) in the patatin-like phospholipase domain containing 3 (PNPLA3) gene and nonalcoholic fatty liver disease. Further replication studies have shown robust associations between PNPLA3 and steatosis, fibrosis/cirrhosis, and hepatocellular carcinoma on a background of metabolic, alcoholic, and viral insults. The PNPLA3 protein has lipase activity towards triglycerides in hepatocytes and retinyl esters in hepatic stellate cells. The I148M substitution leads to a loss of function promoting triglyceride accumulation in hepatocytes. Although PNPLA3 function has been extensively studied, the molecular mechanisms leading to hepatic fibrosis and carcinogenesis remain unclear. This unsuspected association has highlighted the fact that liver fat metabolism may have a major impact on the pathophysiology of liver diseases. Conversely, alone, this locus may have limited predictive value with regard to liver disease outcomes in clinical practice. Additional studies at the genome-wide level will be required to identify new variants associated with liver damage and cancer to explain a greater proportion of the heritability of these phenotypes. Thus, incorporating PNPLA3 and other genetic variants in combination with clinical data will allow for the development of tailored predictive models. This attractive approach should be evaluated in prospective cohorts. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemotherapy between the first and second stages of a two-stage hepatectomy for colorectal liver metastases: should we routinely recommend it?

PubMed

Muratore, Andrea; Zimmitti, Giuseppe; Ribero, Dario; Mellano, Alfredo; Viganò, Luca; Capussotti, Lorenzo

2012-04-01

The aim of the present study is to examine the effect of systemic chemotherapy after the 1st-stage hepatectomy (CT×2) on the progression of disease and dropout rates. A major pitfall of the 2-stage hepatectomy procedure is a high dropout rate after the 1st-stage hepatectomy due to progression of disease (PD). Routine use of CT×2 has been advocated. A total of 47 patients with multiple, bilateral unresectable liver metastases were selected for a 2-stage hepatectomy procedure (±portal vein occlusion). Of the total, 37 patients (78.7%) underwent systemic chemotherapy before the 1st-stage hepatectomy (CT×1) and 25 patients (53.2%) underwent CT×2; PD was significantly more common during CT×2 than during CT×1 (P=.002). Of the 47 patients planned for the 2nd-stage hepatectomy, 36 (76.6%) completed the procedure. Of these 47 patients, 25 (53.2%) showed PD after the 1st-stage hepatectomy, 12 in the CT×2 group and 13 in the no-CT×2 group; administration of CT×2 did not significantly affect the PD rate (P=.561). The overall dropout rate was 23.4% (n=11 patients): 16% in the CT×2 group vs. 31.8% in the no-CT×2 group (P=.303). The routine use of chemotherapy between the 1st- and 2nd-stage hepatectomy does not guarantee lower PD and dropout rates.

Managing non-alcoholic fatty liver disease

PubMed Central

Ngu, Jing Hieng; Goh, George Boon Bee; Poh, Zhongxian; Soetikno, Roy

2016-01-01

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment. PMID:27439352

Diet - liver disease

MedlinePlus

... of toxic waste products. Increasing your intake of carbohydrates to be in proportion with the amount of ... severe liver disease include: Eat large amounts of carbohydrate foods. Carbohydrates should be the major source of ...

Management of alcohol misuse in patients with liver diseases

PubMed Central

Peng, Jennifer L; Patel, Milan Prakash; McGee, Breann; Liang, Tiebing; Chandler, Kristina; Tayarachakul, Sucharat; O’Connor, Sean; Liangpunsakul, Suthat

2017-01-01

Excessive alcohol use not only causes alcoholic liver disease (ALD) but also increases the risk of liver-related mortality in patients who already have other chronic liver diseases. Screening for alcohol misuse or alcohol use disorder (AUD) among patients with underlying liver disease is essential. This clinical review covers what is known about ALD, the impact of alcohol in patients with underlying liver diseases, current management of alcohol misuse and AUD, and the management of alcohol misuse and AUD specifically in patients with liver diseases. Several treatment options for alcohol misuse and AUD exist such as psychosocial intervention and behavioral and pharmacological therapies. The strategies used in the treatment of alcohol misuse and AUD are still applicable in those who consume alcohol and have underlying liver disease. However, certain medications still need to be carefully used due to potentially worsening already compromised liver function. Screening of ongoing alcohol use in subjects with liver disease is important, and prompt intervention is needed to prevent the associated morbidity and mortality from the detrimental effects of continued alcohol use on underlying liver disease. Considering alcoholism is a complex disease, probably a multidisciplinary approach combining psychotherapy and comprehensive medical care will be the most effective. Future research could focus on identifying additional treatment options for addressing the psychotherapy component since the self-determination and will to quit drinking alcohol can play such a crucial role in promoting abstinence. PMID:27940551

Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease.

PubMed

Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies.

PubMed

Pimpin, Laura; Cortez-Pinto, Helena; Negro, Francesco; Corbould, Emily; Lazarus, Jeffrey V; Webber, Laura; Sheron, Nick

2018-05-16

The burden of liver disease in Europe continues to grow. We aimed to describe the epidemiology of liver diseases and their risk factors in European countries, and identify public health interventions that could impact on these risk factors to reduce the burden of liver disease. As part of the HEPAHEALTH project, commissioned by EASL, we extracted information on historical and current prevalence and mortality from national and international literature and databases on liver disease in 35 countries in the WHO European region, as well as historical and recent prevalence data on their main determinants; alcohol consumption, obesity and hepatitis B and C virus infections. We extracted information from peer-reviewed and grey literature to identify public health interventions targeting these risk factors. The epidemiology of liver disease is diverse and countries cluster with similar pictures, although the exact composition of diseases and the trends in risk factors which drive them is varied. Prevalence and mortality data indicate that increasing cirrhosis and liver cancer may be linked to dramatic increases in harmful alcohol consumption in Northern European countries, and viral hepatitis epidemics in Eastern and Southern European countries. Countries with historically low levels of liver disease may experience an increase in non-alcoholic fatty liver disease in the future, given the rise of obesity across the majority of European countries. Interventions exist for curbing harmful alcohol use, reducing obesity, preventing or treating viral hepatitis, and screening for liver disease at an early stage. Liver disease in Europe is a serious issue, with increasing cirrhosis and liver cancer. The public health and hepatology communities are uniquely placed to implement measures aimed at reducing their causes: harmful alcohol consumption, child and adult obesity prevalence and chronic infection with hepatitis viruses, which will in turn reduce the burden of liver disease. The

Psychiatric morbidity in patients with alcoholic liver disease.

PubMed Central

Ewusi-Mensah, I; Saunders, J B; Wodak, A D; Murray, R M; Williams, R

1983-01-01

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients' likelihood of complying with such advice. PMID:6416437

Psychiatric morbidity in patients with alcoholic liver disease.

PubMed

Ewusi-Mensah, I; Saunders, J B; Wodak, A D; Murray, R M; Williams, R

1983-11-12

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients' likelihood of complying with such advice.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

PubMed Central

Firneisz, Gábor

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients. PMID:25083080

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

PubMed

Firneisz, Gábor

2014-07-21

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

Ultrasound Shear Wave Elastography for Liver Disease. A Critical Appraisal of the Many Actors on the Stage.

PubMed

Piscaglia, F; Salvatore, V; Mulazzani, L; Cantisani, V; Schiavone, C

2016-02-01

In the last 12 - 18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(®) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by

TREM2 governs Kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection

PubMed Central

Gonçalves, Lígia Antunes; Rodrigues-Duarte, Lurdes; Rodo, Joana; Vieira de Moraes, Luciana; Marques, Isabel; Penha-Gonçalves, Carlos

2013-01-01

Plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. Here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (TREM2) and MHC class II molecules as determinants of Plasmodium berghei liver stage infection in mice. Locus belr1 confers resistance to malaria liver stage infection. The use of newly derived subcongenic mouse lines allowed to map belr1 to a 4-Mb interval on mouse chromosome 17 that contains the Trem2 gene. We show that Trem2 expression in the nonparenchymal liver cells closely correlates with resistance to liver stage infection, implicating TREM2 as a mediator of the belr1 genetic effect. Trem2-deficient mice are more susceptible to liver stage infection than their WT counterparts. We found that Kupffer cells are the principle cells expressing TREM2 in the liver, and that Trem2−/− Kupffer cells display altered functional activation on exposure to P. berghei sporozoites. TREM2 expression in Kupffer cells contributes to the limitation of parasite expansion in isolated hepatocytes in vitro, potentially explaining the increased susceptibility of Trem2−/− mice to liver stage infection. The MHC locus was also found to control liver parasite burden, possibly owing to the expression of MHC class II molecules in hepatocytes. Our findings implicate unexpected Kupffer–hepatocyte cross-talk in the control Plasmodium liver stage infection and demonstrate that TREM2 is involved in host responses against the malaria parasite. PMID:24218563

TREM2 governs Kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection.

PubMed

Gonçalves, Lígia Antunes; Rodrigues-Duarte, Lurdes; Rodo, Joana; Vieira de Moraes, Luciana; Marques, Isabel; Penha-Gonçalves, Carlos

2013-11-26

Plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. Here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (TREM2) and MHC class II molecules as determinants of Plasmodium berghei liver stage infection in mice. Locus belr1 confers resistance to malaria liver stage infection. The use of newly derived subcongenic mouse lines allowed to map belr1 to a 4-Mb interval on mouse chromosome 17 that contains the Trem2 gene. We show that Trem2 expression in the nonparenchymal liver cells closely correlates with resistance to liver stage infection, implicating TREM2 as a mediator of the belr1 genetic effect. Trem2-deficient mice are more susceptible to liver stage infection than their WT counterparts. We found that Kupffer cells are the principle cells expressing TREM2 in the liver, and that Trem2(-/-) Kupffer cells display altered functional activation on exposure to P. berghei sporozoites. TREM2 expression in Kupffer cells contributes to the limitation of parasite expansion in isolated hepatocytes in vitro, potentially explaining the increased susceptibility of Trem2(-/-) mice to liver stage infection. The MHC locus was also found to control liver parasite burden, possibly owing to the expression of MHC class II molecules in hepatocytes. Our findings implicate unexpected Kupffer-hepatocyte cross-talk in the control Plasmodium liver stage infection and demonstrate that TREM2 is involved in host responses against the malaria parasite.

Alcoholic liver disease

MedlinePlus

... FF, ed. Ferri's Clinical Advisor 2018 . Philadelphia, PA: Elsevier; 2018:59-60. Carithers RL, McClain C. Alcoholic ... Gastrointestinal and Liver Disease . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 86. Haines EJ, Oyama LC. ...

Orthotopic liver transplantation in an adult with cholesterol ester storage disease.

PubMed

Ambler, Graeme K; Hoare, Matthew; Brais, Rebecca; Shaw, Ashley; Butler, Andrew; Flynn, Paul; Deegan, Patrick; Griffiths, William J H

2013-01-01

Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit.

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

PubMed

Wallen, M P; Hall, A; Dias, K A; Ramos, J S; Keating, S E; Woodward, A J; Skinner, T L; Macdonald, G A; Arena, R; Coombes, J S

2017-10-01

Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing. To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease. This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope. Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P <.01) and peak oxygen uptake (P = .02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P = .04). The oxygen uptake efficiency slope was not impacted by beta-blocker use. Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population. © 2017 John Wiley & Sons Ltd.

Ursodeoxycholic acid in chronic liver disease.

PubMed Central

de Caestecker, J S; Jazrawi, R P; Petroni, M L; Northfield, T C

1991-01-01

The hydrophilic bile acid ursodeoxycholic acid has recently been shown to reduce biochemical markers of both cholestasis and hepatocellular damage in patients with chronic liver diseases. The most compelling evidence available is for chronic cholestatic liver diseases, in particular primary biliary cirrhosis, primary sclerosing cholangitis, and cholestasis associated with cystic fibrosis. The effects may be less beneficial in patients with advanced liver disease from these conditions. Data from placebo controlled trials are now available in support of earlier uncontrolled observations, but it is not yet clear whether short term benefit results in an improvement in longterm prognosis. The mechanism of action of the compound seems to reside in its displacement of toxic hydrophobic bile acids from both the bile acid pool and hepatocellular membranes. There may be an independent effect on bile flow, which could be of particular importance in cystic fibrosis, and possibly an effect on the immune system. Ursodeoxycholic acid should now be regarded as occupying a central place in the medical management of chronic cholestatic liver diseases, in particular primary biliary cirrhosis, because it improves cholestasis and reduces hepatocellular damage and it is not toxic. Research should now be targeted on whether treatment with ursodeoxycholic acid, initiated early in cholestatic liver conditions, improves the long-term outcome. PMID:1916492

[Are non-invasive tests going to replace liver biopsy for diagnosis of liver fibrosis?].

PubMed

Restellini, Sophie; Spahr, Laurent

2012-06-27

Liver fibrosis is associated with chronic liver diseases, and may evolve into cirrhosis that may be complicated by liver failure and portal hypertension. Detection and quantification of liver fibrosis is a key point in the follow-up of patients with chronic liver diseases. Liver biopsy is the gold standard method to assess and quantify fibrosis, but its invasiveness is a limiting factor in everyday clinical practice. Non invasive markers using either biological or radiological parameters have been developed and may decrease the need for liver biopsy in some cases. However, information is limited to fibrosis, and cut-offs values and diagnostic accuracies for significant fibrosis may vary according to the etiology of liver disease. Liver biopsy allows the assessment of intermediate stages of fibrosis and describes accompanying lesions.

Liver disease in adult transfusion-dependent beta-thalassaemic patients: investigating the role of iron overload and chronic HCV infection.

PubMed

Kountouras, Dimitrios; Tsagarakis, Nikolaos J; Fatourou, Evangelia; Dalagiorgos, Efthimios; Chrysanthos, Nikolaos; Berdoussi, Helen; Vgontza, Niki; Karagiorga, Markissia; Lagiandreou, Athanasios; Kaligeros, Konstantinos; Voskaridou, Ersi; Roussou, Paraskevi; Diamanti-Kandarakis, Evanthia; Koskinas, John

2013-03-01

Iron overload and hepatitis-C virus (HCV) infection, have been implicated in the evolution of liver disease, in patients with transfusion-dependent beta-thalassaemia major (BTM). However, the impact of these factors in late stages of liver disease in adults with BTM, has not been extensively studied. To investigate serum indices of iron overload, HCV infection and liver disease, in a cohort of 211 adult Greek patients with BTM, in relation with the findings from liver biopsies. In this cross-sectional study, 211 patients with BTM were enrolled and studied, in relation with HCV infection, ferritin, transaminases, chelation treatment and antiviral treatment. Based on 109 patients biopsied, we correlated liver fibrosis, haemosiderosis and inflammation, with serum indices and HCV status Among all patients, 74.4% were anti-HCV positive (HCV+). Ferritin was positively correlated with transaminases and negatively correlated with age, while it was not significantly different among HCV+ and HCV- patients. Among the HCV+ patients, 55.4% reported antiviral treatment, while genotype 1 predominated. In a subfraction of 109 patients, in which liver biopsy was performed, 89% were HCV+ and 11% HCV-. Fibrosis was significantly correlated with age (P = 0.046), AST (P = 0.004), ALT (P = 0.044) and inflammation (P < 0.001). Advanced fibrosis was present with even minimal haemosiderosis, independently of ferritin values or HCV history. These data suggest that in the late stages of liver disease in BTM patients, iron overload may be the critical determinant, since fibrosis is related to the minimal haemosiderosis, independently of HCV history. © 2012 John Wiley & Sons A/S.

LiverAtlas: a unique integrated knowledge database for systems-level research of liver and hepatic disease.

PubMed

Zhang, Yanqiong; Yang, Chunyuan; Wang, Shaochuang; Chen, Tao; Li, Mansheng; Wang, Xue; Li, Dongsheng; Wang, Kang; Ma, Jie; Wu, Songfeng; Zhang, Xueli; Zhu, Yunping; Wu, Jinsheng; He, Fuchu

2013-09-01

A large amount of liver-related physiological and pathological data exist in publicly available biological and bibliographic databases, which are usually far from comprehensive or integrated. Data collection, integration and mining processes pose a great challenge to scientific researchers and clinicians interested in the liver. To address these problems, we constructed LiverAtlas (http://liveratlas.hupo.org.cn), a comprehensive resource of biomedical knowledge related to the liver and various hepatic diseases by incorporating 53 databases. In the present version, LiverAtlas covers data on liver-related genomics, transcriptomics, proteomics, metabolomics and hepatic diseases. Additionally, LiverAtlas provides a wealth of manually curated information, relevant literature citations and cross-references to other databases. Importantly, an expert-confirmed Human Liver Disease Ontology, including relevant information for 227 types of hepatic disease, has been constructed and is used to annotate LiverAtlas data. Furthermore, we have demonstrated two examples of applying LiverAtlas data to identify candidate markers for hepatocellular carcinoma (HCC) at the systems level and to develop a systems biology-based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC differential diagnosis. LiverAtlas is the most comprehensive liver and hepatic disease resource, which helps biologists and clinicians to analyse their data at the systems level and will contribute much to the biomarker discovery and diagnostic performance enhancement for liver diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nonalcoholic fatty liver disease and vascular disease: State-of-the-art

PubMed Central

Fargion, Silvia; Porzio, Marianna; Fracanzani, Anna Ludovica

2014-01-01

Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular

Extracellular Matrix and Liver Disease

PubMed Central

Arriazu, Elena; Ruiz de Galarreta, Marina; Cubero, Francisco Javier; Varela-Rey, Marta; Pérez de Obanos, María Pilar; Leung, Tung Ming; Lopategi, Aritz; Benedicto, Aitor; Abraham-Enachescu, Ioana

2014-01-01

Abstract Significance: The extracellular matrix (ECM) is a dynamic microenvironment that undergoes continuous remodeling, particularly during injury and wound healing. Chronic liver injury of many different etiologies such as viral hepatitis, alcohol abuse, drug-induced liver injury, obesity and insulin resistance, metabolic disorders, and autoimmune disease is characterized by excessive deposition of ECM proteins in response to persistent liver damage. Critical Issues: This review describes the main collagenous and noncollagenous components from the ECM that play a significant role in pathological matrix deposition during liver disease. We define how increased myofibroblasts (MF) from different origins are at the forefront of liver fibrosis and how liver cell-specific regulation of the complex scarring process occurs. Recent Advances: Particular attention is paid to the role of cytokines, growth factors, reactive oxygen species, and newly identified matricellular proteins in the regulation of fibrillar type I collagen, a field to which our laboratory has significantly contributed over the years. We compile data from recent literature on the potential mechanisms driving fibrosis resolution such as MF’ apoptosis, senescence, and reversal to quiescence. Future Directions: We conclude with a brief description of how epigenetics, an evolving field, can regulate the behavior of MF and of how new “omics” tools may advance our understanding of the mechanisms by which the fibrogenic response to liver injury occurs. Antioxid. Redox Signal. 21, 1078–1097. PMID:24219114

Coeliac disease in autoimmune liver disease: a cross-sectional study and a systematic review.

PubMed

Mirzaagha, Foroozandeh; Azali, Sepideh Hagh; Islami, Farhad; Zamani, Farhad; Khalilipour, Elias; Khatibian, Morteza; Malekzadeh, Reza

2010-09-01

Several studies have reported an association between coeliac disease and autoimmune liver disease, but there is little information on the prevalence of coeliac disease in certain autoimmune liver diseases, particularly from non-European, non-American countries. To investigate prevalence of coeliac disease in autoimmune liver disease in Iran and to summarize previous literature. We investigated prevalence of coeliac disease among 100 autoimmune liver disease patients and compared it with the prevalence in healthy individuals. We also performed an extensive search of the English literature in PubMed Database. We found substantially elevated prevalence of coeliac disease in patients with overlap syndrome (10-15%) compared to the general population (0.1-1%). To a lesser extent, the prevalence was high in patients with autoimmune hepatitis (2-4%). In our systematic review, prevalence of coeliac disease in autoimmune hepatitis in the majority of studies was 4% or more; several studies also reported such prevalence in primary biliary cirrhosis. Since coeliac disease is common among patients with autoimmune liver disease, screening autoimmune liver disease patients for coeliac disease is indicated. Although the magnitude of benefit from a gluten-free diet in reversing autoimmune liver disease in patients with coeliac disease is controversial, it may reduce the risk of further complications of coeliac disease. Copyright (c) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Ambiguous roles of innate lymphoid cells in chronic development of liver diseases.

PubMed

Shen, Yue; Li, Jing; Wang, Si-Qi; Jiang, Wei

2018-05-14

Innate lymphoid cells (ILCs) are defined as a distinct arm of innate immunity. According to their profile of secreted cytokines and lineage-specific transcriptional factors, ILCs can be categorized into the following three groups: group 1 ILCs (including natural killer (NK) cells and ILC1s) are dependent on T-bet and can produce interferon-γ; group 2 ILCs (ILC2s) are dependent on GATA3 and can produce type 2 cytokines, including interleukin (IL)-5 and IL-13; and, group 3 ILCs (including lymphoid tissue-like cells and ILC3s) are dependent on RORγt and can produce IL-22 and IL-17. Collaborative with adaptive immunity, ILCs are highly reactive innate effectors that promptly orchestrate immunity, inflammation and tissue repair. Dysregulation of ILCs might result in inflammatory disorders. Evidence regarding the function of intrahepatic ILCs is emerging from longitudinal studies of inflammatory liver diseases wherein they exert both physiological and pathological functions, including immune homeostasis, defenses and surveillance. Their overall effect on the liver depends on the balance of their proinflammatory and antiinflammatory populations, specific microenvironment and stages of immune responses. Here, we review the current data about ILCs in chronic liver disease progression, to reveal their roles in different stages as well as to discuss their therapeutic potency as intervention targets.

Ambiguous roles of innate lymphoid cells in chronic development of liver diseases

PubMed Central

Shen, Yue; Li, Jing; Wang, Si-Qi; Jiang, Wei

2018-01-01

Innate lymphoid cells (ILCs) are defined as a distinct arm of innate immunity. According to their profile of secreted cytokines and lineage-specific transcriptional factors, ILCs can be categorized into the following three groups: group 1 ILCs (including natural killer (NK) cells and ILC1s) are dependent on T-bet and can produce interferon-γ; group 2 ILCs (ILC2s) are dependent on GATA3 and can produce type 2 cytokines, including interleukin (IL)-5 and IL-13; and, group 3 ILCs (including lymphoid tissue-like cells and ILC3s) are dependent on RORγt and can produce IL-22 and IL-17. Collaborative with adaptive immunity, ILCs are highly reactive innate effectors that promptly orchestrate immunity, inflammation and tissue repair. Dysregulation of ILCs might result in inflammatory disorders. Evidence regarding the function of intrahepatic ILCs is emerging from longitudinal studies of inflammatory liver diseases wherein they exert both physiological and pathological functions, including immune homeostasis, defenses and surveillance. Their overall effect on the liver depends on the balance of their proinflammatory and antiinflammatory populations, specific microenvironment and stages of immune responses. Here, we review the current data about ILCs in chronic liver disease progression, to reveal their roles in different stages as well as to discuss their therapeutic potency as intervention targets. PMID:29760540

Comparison of the sequential organ failure assessment score with the King's College Hospital criteria and the model for end-stage liver disease score for the prognosis of acetaminophen-induced acute liver failure.

PubMed

Cholongitas, Evangelos; Theocharidou, Eleni; Vasianopoulou, Panayota; Betrosian, Alex; Shaw, Steve; Patch, David; O'Beirne, James; Agarwal, Banwari; Burroughs, Andrew K

2012-04-01

Acetaminophen-induced acute liver failure (ALF) is a complex multiorgan illness. An assessment of the prognosis is essential for the accurate identification of patients for whom survival without liver transplantation (LT) is unlikely. The aims of this study were the comparison of prognostic models [King's College Hospital (KCH), Model for End-Stage Liver Disease, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II)] and the identification of independent prognostic indicators of outcome. We evaluated consecutive patients with severe acetaminophen-induced ALF who were admitted to the intensive care unit. At admission, demographic, clinical, and laboratory parameters were recorded. The discriminative ability of each prognostic score at the baseline was evaluated with the area under the receiver operating characteristic curve (AUC). In addition, using a multiple logistic regression, we assessed independent factors associated with outcome. In all, 125 consecutive patients with acetaminophen-induced ALF were evaluated: 67 patients (54%) survived with conservative medical management (group 1), and 58 patients (46%) either died without LT (28%) or underwent LT (18%; group 2). Group 1 patients had significantly lower median APACHE II (10 versus 14) and SOFA scores (9 versus 12) than group 2 patients (P < 0.001). The independent indicators associated with death or LT were a longer prothrombin time (P = 0.007), the inspiratory oxygen concentration (P = 0.005), and the lactate level at 12 hours (P < 0.001). The KCH criteria had the highest specificity (83%) but the lowest sensitivity (47%), and the SOFA score had the best discriminative ability (AUC = 0.79). In conclusion, for patients with acetaminophen-induced ALF, the SOFA score performed better than the other prognostic scores, and this reflected the presence of multiorgan dysfunction. A further evaluation of SOFA with the KCH criteria is warranted. Copyright © 2012

Pathology and biopsy assessment of non-alcoholic fatty liver disease.

PubMed

Straub, Beate Katharina; Schirmacher, Peter

2010-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases in Western industrialized countries with dramatically rising incidence. The diagnosis of NAFLD requires the existence of steatosis in the absence of significant alcohol consumption. In cases of relevant inflammation pathogenetically linked to steatosis, it is termed non-alcoholic steatohepatitis (NASH). While pure steatosis represents a relatively harmless and rapidly reversible condition without a significant tendency to progression, NASH carries a significant morbidity and progression risk. Noninvasive methods neither reliably establish the diagnosis nor define the extent of disease in NASH, making histopathology the diagnostic gold standard. Since current therapeutic options in NASH are limited, indication for biopsy is made in the clinical context, predominantly in unclear clinical constellations, prior to invasive measures, for follow-up purposes and in the context of clinical studies. Histological hallmarks of NASH are steatosis, hepatocellular ballooning (with and without Mallory-Denk bodies), necroinflammation, and progressing disease a characteristic with perisinusoidal fibrosis. For semiquantitative assessment of necroinflammation (grading) and fibrosis (staging), a score has recently been implemented. Although histology does not reliably distinguish alcoholic steatohepatitis/alcoholic fatty liver disease from NASH/NAFLD, it may give valuable hints. NASH has a tendency for more steatosis, the so-called glycogenated nuclei, and less necroinflammatory activity. Future development of biopsy diagnosis will be coupled to the development of differential systemic therapeutic approaches. Especially in the context of clinical studies, detailed histological evaluation should be considered for the detection of predictive parameters. Copyright 2010 S. Karger AG, Basel.

Quality of life in patients with nonalcoholic fatty liver disease in combination with essential hypertension considering taste sensitivity to sodium chloride.

PubMed

Mashura, Hanna Y; Hanych, Taras M; Rishko, Alexander A

2016-01-01

Nonalcoholic fatty liver disease and hypertensive disease - is the most common combination of abnormalities that occur in people suffering from metabolic syndrome. Their combination not only causes concurrent damage of the liver and the heart, caused by common pathogenic beginning, and also mutually complicate the disease course of each other. The leading role in the development of nonalcoholic fatty liver disease belongs to abdominal obesity and insulin resistance, and is seen as a manifestation of liver disease in metabolic syndrome. Genetic predisposition, lifestyle, improper nutrition, including excessive use of sodium chloride, lead to excessive formation of visceral adipose tissue with development of abdominal obesity, which is a likely criterion of insulin resistance. The long course of nonalcoholic fatty liver disease in combination with essential hypertension in excessive consumption of sodium chloride may negatively affect their quality of life. The aim of the study is to find out the features of quality of life in patients with nonalcoholic fatty liver disease in combination with hypertensive disease with different taste sensitivity to sodium chloride. We have investigated the quality of life of 65 patients with nonalcoholic fatty liver disease in combination with hypertensive disease II stage with different taste sensitivity to sodium chloride. Salt taste sensitivity threshold to sodium chloride is determined by the method of R. Henkin. Assessment of quality of life was performed using the Ukrainian version of the questionnaire Medical Outcomes Study Short Form 36 (MO S SF-36). Was revealed that in patients with nonalcoholic fatty liver disease in combination with hypertensive disease II stage with high salt taste sensitivity threshold observed the decline in the quality of life that manifests as a decline in physical condition (especially of the physical functioning, physical role functioning and general health perceptions) and mental health

Quantification of liver fat: A comprehensive review.

PubMed

Goceri, Evgin; Shah, Zarine K; Layman, Rick; Jiang, Xia; Gurcan, Metin N

2016-04-01

Fat accumulation in the liver causes metabolic diseases such as obesity, hypertension, diabetes or dyslipidemia by affecting insulin resistance, and increasing the risk of cardiac complications and cardiovascular disease mortality. Fatty liver diseases are often reversible in their early stage; therefore, there is a recognized need to detect their presence and to assess its severity to recognize fat-related functional abnormalities in the liver. This is crucial in evaluating living liver donors prior to transplantation because fat content in the liver can change liver regeneration in the recipient and donor. There are several methods to diagnose fatty liver, measure the amount of fat, and to classify and stage liver diseases (e.g. hepatic steatosis, steatohepatitis, fibrosis and cirrhosis): biopsy (the gold-standard procedure), clinical (medical physics based) and image analysis (semi or fully automated approaches). Liver biopsy has many drawbacks: it is invasive, inappropriate for monitoring (i.e., repeated evaluation), and assessment of steatosis is somewhat subjective. Qualitative biomarkers are mostly insufficient for accurate detection since fat has to be quantified by a varying threshold to measure disease severity. Therefore, a quantitative biomarker is required for detection of steatosis, accurate measurement of severity of diseases, clinical decision-making, prognosis and longitudinal monitoring of therapy. This study presents a comprehensive review of both clinical and automated image analysis based approaches to quantify liver fat and evaluate fatty liver diseases from different medical imaging modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oral Anticoagulation in Patients With Liver Disease.

PubMed

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?

PubMed Central

Mikolasevic, Ivana; Filipec-Kanizaj, Tajana; Mijic, Maja; Jakopcic, Ivan; Milic, Sandra; Hrstic, Irena; Sobocan, Nikola; Stimac, Davor; Burra, Patrizia

2018-01-01

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation (LT), on patients on the waiting list for transplant, on post-transplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of MetS and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population. PMID:29662288

Clinico-biochemical correlation to histological findings in alcoholic liver disease: a single centre study from eastern India.

PubMed

Ray, Sayantan; Khanra, Dibbendhu; Sonthalia, Nikhil; Kundu, Supratip; Biswas, Kaushik; Talukdar, Arunansu; Saha, Manjari; Bera, Himel

2014-10-01

Alcoholism is a health problem not only in developed countries but also in developing countries. Cirrhosis due to alcohol is a common cause of death among individuals abusing alcohol. A better knowledge of the spectrum of alcoholic liver diseases, its clinical, biochemical and histopathological features could result in early detection and prevention of alcoholic liver diseases before it's catastrophic and life threatening effects. A total of 200 patients with alcoholic liver diseases were studied with respect to alcohol consumption, clinical features, biochemical and histopathological changes. The clinical features, biochemical parameters, and histopathology of liver including Ishak's modified histological activity index (HAI) were correlated with the amount and duration of alcohol consumed. Majority of the patients were in the age group of 40-49 years and all the cases were males. Majority consumed alcohol of about 75-90 grams per day for a duration of 10-12 years. Anorexia and jaundice were the most common symptom and clinical finding respectively. Hyperbilirubinemia and hypoalbuminemia were the most common abnormalities observed in liver function tests. Advanced HAI stages with features of cirrhosis were most frequent histo-pathological finding noted in this study. Clinico-biochemical profile was significantly correlated with degree of alcohol ingestion as well as with liver histopathology. The wide prevalence of alcoholic liver disease including cirrhosis among Indian males was noted with significantly lower quantity and duration of alcohol ingestion. The severity of liver damage is directly proportional to the quantity and duration of alcohol consumed. Clinical features and biochemical changes may forecast the liver histopathology among the patients of alcoholic liver disease.

Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice.

PubMed

Al-Quraishy, Saleh; Dkhil, Mohamed A; Abdel-Baki, Abdel-Azeem S; Ghanjati, Foued; Erichsen, Lars; Santourlidis, Simeon; Wunderlich, Frank; Araúzo-Bravo, Marcos J

2017-05-01

Epigenetic mechanisms such as DNA methylation are increasingly recognized to be critical for vaccination efficacy and outcome of different infectious diseases, but corresponding information is scarcely available for host defense against malaria. In the experimental blood-stage malaria Plasmodium chabaudi, we investigate the possible effects of a blood-stage vaccine on DNA methylation of gene promoters in the liver, known as effector against blood-stage malaria, using DNA methylation microarrays. Naturally susceptible Balb/c mice acquire, by protective vaccination, the potency to survive P. chabaudi malaria and, concomitantly, modifications of constitutive DNA methylation of promoters of numerous genes in the liver; specifically, promoters of 256 genes are hyper(=up)- and 345 genes are hypo(=down)-methylated (p < 0.05). Protective vaccination also leads to changes in promoter DNA methylation upon challenge with P. chabaudi at peak parasitemia on day 8 post infection (p.i.), when 571 and 1013 gene promoters are up- and down-methylated, respectively, in relation to constitutive DNA methylation (p < 0.05). Gene set enrichment analyses reveal that both vaccination and P. chabaudi infections mainly modify promoters of those genes which are most statistically enriched with functions relating to regulation of transcription. Genes with down-methylated promoters encompass those encoding CX3CL1, GP130, and GATA2, known to be involved in monocyte recruitment, IL-6 trans-signaling, and onset of erythropoiesis, respectively. Our data suggest that vaccination may epigenetically improve parts of several effector functions of the liver against blood-stage malaria, as, e.g., recruitment of monocyte/macrophage to the liver accelerated liver regeneration and extramedullary hepatic erythropoiesis, thus leading to self-healing of otherwise lethal P. chabaudi blood-stage malaria.

HIV/HCV Co-infection, Liver Disease Progression, and Age-Related IGF-1 Decline.

PubMed

Quinn, Jeffrey; Astemborski, Jacquie; Mehta, Shruti H; Kirk, Gregory D; Thomas, David L; Balagopal, Ashwin

2017-01-01

We have previously reported that persons co-infected with HIV and hepatitis C virus (HCV) had liver disease stages similar to HIV-uninfected individuals who were approximately 10 years older. Insulin-like growth factor 1(IGF-1) levels have long been known to decline with advancing age in humans and non-humans alike. We examined whether HIV infection affects the expected decline in IGF-1 in persons with chronic hepatitis C virus (HCV) infection and if that alteration in IGF-1 decline contributes to the link between HIV, aging, and liver disease progression. A total of 553 individuals with HCV infection were studied from the AIDS Linked to the Intravenous Experience (ALIVE) cohort for whom more than 10 years of follow-up was available. Serum IGF-1 levels were determined by ELISA and evaluated according to baseline characteristics and over time by HIV status and liver disease progression. Linear regression with generalized estimating equations was used to determine whether IGF-1 decline over time was independently associated with liver disease progression. Baseline IGF-1 levels were strongly associated with age ( P < 0.0001) but not with gender or HIV infection. Levels of IGF-1 declined at a rate of -1.75 ng/mL each year in HCV mono-infected individuals and at a rate of -1.23 ng/mL each year in HIV/HCV co-infected individuals ( P < 0.05). In a multivariable linear regression model, progression of liver fibrosis was associated with HIV infection and age, as well as with a slower rate of IGF-1 decline ( P = 0.001); however, the rate of IGF-1 decline did not alter the strength of the associations between HIV, liver disease, and age. The normal decline in IGF-1 levels with age was attenuated in HIV/HCV co-infected individuals compared to those with HCV mono-infection, and slower IGF-1 decline was independently associated with liver disease progression.

The global burden of liver disease: the major impact of China.

PubMed

Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang

2014-12-01

Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its "leader in liver diseases" title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. © 2014 by the American Association for the Study of Liver Diseases.

Genetics of liver disease: From pathophysiology to clinical practice.

PubMed

Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

2015-04-01

Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis, End-Stage Renal Disease and Transplant Medicine.

PubMed

Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H; Heinzow, Hauke S

2015-08-05

Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts.

Discharge Disposition After Stroke in Patients With Liver Disease.

PubMed

Parikh, Neal S; Merkler, Alexander E; Schneider, Yecheskel; Navi, Babak B; Kamel, Hooman

2017-02-01

Liver disease is associated with both hemorrhagic and thrombotic processes, including an elevated risk of intracranial hemorrhage. We sought to assess the relationship between liver disease and outcomes after stroke, as measured by discharge disposition. Using administrative claims data, we identified a cohort of patients hospitalized with stroke in California, Florida, and New York from 2005 to 2013. The predictor variable was liver disease. All diagnoses were defined using validated diagnosis codes. Ordinal logistic regression was used to analyze the association between liver disease and worsening discharge disposition: home, nursing/rehabilitation facility, or death. Secondarily, multiple logistic regression was used to analyze the association between liver disease and in-hospital mortality. Models were adjusted for demographics, vascular risk factors, and comorbidities. We identified 121 428 patients with intracerebral hemorrhage and 703 918 with ischemic stroke. Liver disease was documented in 13 584 patients (1.7%). Liver disease was associated with worse discharge disposition after both intracerebral hemorrhage (global odds ratio, 1.28; 95% confidence interval, 1.19-1.38) and ischemic stroke (odds ratio, 1.23; 95% confidence interval, 1.17-1.29). Similarly, liver disease was associated with in-hospital death after both intracerebral hemorrhage (odds ratio, 1.33; 95% confidence interval, 1.23-1.44) and ischemic stroke (odds ratio, 1.60; 95% confidence interval, 1.51-1.71). Liver disease was associated with worse hospital discharge disposition and in-hospital mortality after stroke, suggesting worse functional outcomes. © 2016 American Heart Association, Inc.

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

Hyaluronic acid concentration in liver diseases.

PubMed

Gudowska, Monika; Gruszewska, Ewa; Panasiuk, Anatol; Cylwik, Bogdan; Flisiak, Robert; Świderska, Magdalena; Szmitkowski, Maciej; Chrostek, Lech

2016-11-01

The aim of this study was to evaluate the effect of liver diseases of different etiologies and clinical severity of liver cirrhosis on the serum level of hyaluronic acid. The results were compared with noninvasive markers of liver fibrosis: APRI, GAPRI, HAPRI, FIB-4 and Forn's index. Serum samples were obtained from 20 healthy volunteers and patients suffering from alcoholic cirrhosis (AC)-57 patients, non-alcoholic cirrhosis (NAC)-30 and toxic hepatitis (HT)-22. Cirrhotic patients were classified according to Child-Pugh score. Hyaluronic acid concentration was measured by the immunochemical method. Non-patented indicators were calculated using special formulas. The mean serum hyaluronic acid concentration was significantly higher in AC, NAC and HT group in comparison with the control group. There were significant differences in the serum hyaluronic acid levels between liver diseases, and in AC they were significantly higher than those in NAC and HT group. The serum hyaluronic acid level differs significantly due to the severity of cirrhosis and was the highest in Child-Pugh class C. The sensitivity, specificity, accuracy, positive and negative predictive values and the area under the ROC curve for hyaluronic acid and all non-patented algorithms were high and similar to each other. We conclude that the concentration of hyaluronic acid changes in liver diseases and is affected by the severity of liver cirrhosis. Serum hyaluronic acid should be considered as a good marker for noninvasive diagnosis of liver damage, but the combination of markers is more useful.

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.

Nutrition management in chronic liver disease.

PubMed

Bavdekar, Ashish; Bhave, Sheila; Pandit, Anand

2002-05-01

Liver has a central role in nutritional homeostasis and any liver disease leads to abnormalities in nutrient metabolism and subsequent malnutrition. All children with chronic liver disease (CLD) must undergo a periodic nutritional assessment--medical history, anthropometry esp. skinfold thickness and mid-arm circumference, and biochemical estimation of body nutrients. Nutritional rehabilitation is catered to the individual child but generally the caloric intake is increased to 130% of RDA by adding glucose polymers and/or MCT oil (coconut oil) with essential fatty acid supplementation (sunflower oil). The enteral route is preferred and occasionally nasogastric and/or nocturnal feeding are required to ensure an adequate intake. Proteins rich in branched chain amino acids are given in moderation (2-3 gm/kg/day) in compensated cirrhotics unless encephalopathy occurs when protein restriction may be necessary (1 gm/kg/day). Fat-soluble vitamins are supplemented in large quantities esp. in cholestasis along with other vitamins and minerals. Dietary therapy is the mainstay of management of some metabolic liver diseases and may be curative in disorders like galactosemia, fructosemia and glycogen storage disorders. Pre and postoperative nutritional support is an important factor in improving survival after liver transplantation.

APSA Awardee Submission: Tumor/cancer stem cell marker doublecortin-like kinase 1 in liver diseases.

PubMed

Nguyen, Charles B; Houchen, Courtney W; Ali, Naushad

2017-02-01

Liver diseases are the fourth leading cause of mortality among adults in the United States. Patients with chronic liver diseases such as viral hepatitis, fibrosis, and cirrhosis have significantly higher risks of developing hepatocellular carcinoma (HCC). With a dismal five-year survival rate of 11%, HCC is the third most common cause of cancer-related deaths worldwide. Regardless of the underlying cause, late presentation and a lack of effective therapy are the major impediments for successful treatment of HCC. Therefore, there is a considerable interest in developing new strategies for the prevention and treatment of chronic liver diseases at the early stages. Cancer stem cells (CSCs), a small cell subpopulation in a tumor, exhibit unlimited self-renewal and differentiation capacity. These cells are believed to play pivotal roles in the initiation, growth, metastasis, and drug-resistance of tumors. In this review, we will briefly discuss pivotal roles of the CSC marker doublecortin-like kinase 1 (DCLK1) in hepatic tumorigenesis. Recent evidence suggests that anti-DCLK1 strategies hold promising clinical potential for the treatment of cancers of the liver, pancreas, and colon.

Waitlist Outcomes for Patients Relisted Following Failed Donation After Cardiac Death Liver Transplant: Implications for Awarding Model for End-Stage Liver Disease Exception Scores.

PubMed

Croome, K P; Lee, D D; Nguyen, J H; Keaveny, A P; Taner, C B

2017-09-01

Understanding of outcomes for patients relisted for ischemic cholangiopathy following a donation after cardiac death (DCD) liver transplant (LT) will help standardization of a Model for End-Stage Liver Disease exception scheme for retransplantation. Early relisting (E-RL) for DCD graft failure caused by primary nonfunction (PNF) or hepatic artery thrombosis (HAT) was defined as relisting ≤14 days after DCD LT, and late relisting (L-RL) due to biliary complications was defined as relisting 14 days to 3 years after DCD LT. Of 3908 DCD LTs performed nationally between 2002 and 2016, 540 (13.8%) patients were relisted within 3 years of transplant (168 [4.3%] in the E-RL group, 372 [9.5%] in the L-RL group). The E-RL and L-RL groups had waitlist mortality rates of 15.4% and 10.5%, respectively, at 3 mo and 16.1% and 14.3%, respectively, at 1 year. Waitlist mortality in the L-RL group was higher than mortality and delisted rates for patients with exception points for both hepatocellular carcinoma (HCC) and hepatopulmonary syndrome (HPS) at 3- to 12-mo time points (p < 0.001). Waitlist outcomes differed in patients with early DCD graft failure caused by PNF or HAT compared with those with late DCD graft failure attributed to biliary complications. In L-RL, higher rates of waitlist mortality were noted compared with patients listed with exception points for HCC or HPS. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

The role of ultrasound elastographic techniques in chronic liver disease: current status and future perspectives.

PubMed

Piscaglia, Fabio; Marinelli, Sara; Bota, Simona; Serra, Carla; Venerandi, Laura; Leoni, Simona; Salvatore, Veronica

2014-03-01

This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment. The characterization of focal liver lesions and the prognostic role of the elastographic technique in the prediction of complications of cirrhosis are still under investigation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The emerging role of mast cells in liver disease.

PubMed

Jarido, Veronica; Kennedy, Lindsey; Hargrove, Laura; Demieville, Jennifer; Thomson, Joanne; Stephenson, Kristen; Francis, Heather

2017-08-01

The depth of our knowledge regarding mast cells has widened exponentially in the last 20 years. Once thought to be only important for allergy-mediated events, mast cells are now recognized to be important regulators of a number of pathological processes. The revelation that mast cells can influence organs, tissues, and cells has increased interest in mast cell research during liver disease. The purpose of this review is to refresh the reader's knowledge of the development, type, and location of mast cells and to review recent work that demonstrates the role of hepatic mast cells during diseased states. This review focuses primarily on liver diseases and mast cells during autoimmune disease, hepatitis, fatty liver disease, liver cancer, and aging in the liver. Overall, these studies demonstrate the potential role of mast cells in disease progression.