Leading Indication For Liver Transplantation Research Articles

Key molecular pathways in the progression of non-alcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide and also become an emerging risk factor for liver-related complications, such as cirrhosis and hepatocellular carcinoma (HCC). The liver-related burden of NASH is likely to increase and nonalcoholic steatohepatitis (NASH) is probably to be the leading indication for liver transplantation by 2020, as a consequence of increased disease prevalence and of the lack of an effective treatment. The first step in the NAFLD development is represented by fat accumulation in the liver, a condition that is commonly associated with features of the metabolic syndrome. Notably, it has been acknowledged that the step from nonalcoholic fatty liver (NAFL) to NASH is key step in the NASH formation, and the mechanisms behind this transition have been extensively studied. Emerging evidence indicates that innate immunity is a driving force in NAFLD progression because it directly regulates all key pathogenic features of the disease processes, including metabolic dysregulation, inflammation, and fibrosis. In this review, we summarize the currently available signaling pathways of NASH formation, including oxidative stress, NOD-like receptors (NLRs), mitochondria-associated pathways, Toll-like receptors (TLRs), nuclear receptors, and other signal pathways, for the aim of a better understanding of this disease.

Alcoholic Liver Disease Replaces Hepatitis C Virus Infection as the Leading Indication for Liver Transplantation in the United States

Alcoholic Liver Disease Replaces Hepatitis C Virus Infection as the Leading Indication for Liver Transplantation in the United States

Cancer prevention through better sleeping habits: the circadian clock and hepatocellular cancer

© Translational Cancer Research. All rights reserved. tcr.amegroups.com Transl Cancer Res 2017 The incidence of hepatocellular cancer (HCC) has been steadily increasing in the United States for the last several decades, and currently HCC constitutes the fastest growing cause of cancer deaths in the country. The majority of HCC occurs in the setting of chronic liver disease with viral infections [hepatitis B virus (HBV) or hepatitis C virus (HCV)] and alcohol-related liver disease being the most common risk factors. Recently non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been recognized as conditions predisposing to the development of end stage liver disease and HCC (1). It is estimated that in the next 10 years, NASH will become the leading indication for liver transplantation in the Western world (1-2).

1146 THE EFFECTS OF BROADLY NEUTRALIZING ANTIBODIES IN EXPERIMENTAL HCV INFECTION

Hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the US. The graft is universally infected after transplantation, and this typically results in accelerated fibrosis progression. Current HCV therapies have poor efficacy and tolerability in the challenging pre- and posttransplant populations. Alternative pre- and post-transplantation measures are needed to prevent graft infection. One potential strategy to prevent such infection is the administration of potent broadly neutralizing antibodies (bnAbs).

Hepatitis C virus entry and glucocorticosteroids

Pole Hepato-digestif, Hopitaux Universitaires de Strasbourg, Strasbourg, FranceCOMMENTARY ON:Glucocorticosteroids increase cell entry by hepatitis C virus.Ciesek S, Steinmann E, Iken M, Ott M, Helfritz FA, Wappler I,Manns MP, Wedemeyer H, Pietschmann T. Gastroenterology.2010;138:1875–84. Copyright (2010). Abstract reprinted withpermission from Elsevier.http://www.ncbi.nlm.nih.gov/pubmed/20152835Background & Aims:Corticosteroids are used as immunosuppres-sants in patients with autoimmune disorders and transplant recipi-ents. However, these drugs worsen hepatitis C virus (HCV)recurrence after liver transplantation, suggesting that they maydirectly exacerbate HCV infection.Methods:The influence of immunosuppressive drugs on HCV repli-cation, assembly, and entry was assessed in Huh-7.5 cells and pri-mary human hepatocytes using cell culture- and patient-derivedHCV. Replication was quantified by immunofluorescence, luciferaseassays, quantitative reverse-transcriptase polymerase chain reac-tion, or core enzyme-linked immunosorbent assays. Expression ofHCV entry factors was evaluated by cell sorting and immunoblotanalyses.Results:Glucocorticosteroids slightly reduced HCV RNA replicationbut increased efficiency of HCV entry by up to 10-fold. This was inde-pendent of HCV genotype but specific to HCV because vesicular sto-matitis virus glycoprotein-dependent infection was not affected bythese drugs. The increase in HCV entry was accompanied by up-reg-ulation of messenger RNA and protein levels of occludin and thescavenger receptor class B type I – two host cell proteins requiredfor HCV infection;increase of entry by glucocorticosteroids wasablated by RU-486, an inhibitor of glucocorticosteroid signalling.Glucocorticosteroids increased propagation of cell culture-derivedHCV approximately 5- to 10-fold in partially differentiated humanhepatoma cells and increased infection of primary human hepato-cytes by cell culture- and patient-derived HCV.Conclusions:Glucocorticosteroides specifically increase HCV entryby up-regulating the cell entry factors occludin and scavenger recep-tor class B type I. Our data suggest that the potential effects of high-dose glucocorticosteroids on HCV infection in vivo may be due toincreased HCV dissemination. 2010 European Association for the Study of the Liver. Publishedby Elsevier B.V. All rights reserved.Hepatitis C-associated liver failure is the leading indication forliver transplantation (LT). Hepatitis C virus (HCV) re-infection ofthe liver graft occurs immediately after transplantation with arapid increase in HCV RNA post-transplantation [1]. HCV recur-rence is characterized by accelerated histological progression,with up to 30% of patients developing cirrhosis after five yearsfollowing LT [1]. A prophylactic strategy for prevention of re-infection is lacking and interferon-based antiviral therapies havelimited efficacy and tolerability in LT recipients [2]. Thus, recur-rent liver disease with poor outcome has become an increasingproblem facing hepatologists and transplant surgeons [2].Viral and host factors contribute to HCV re-infection and pro-gression of liver disease. Viral factors include efficiency of entry,replication, and production of progeny virus. Host factors includeimmune responses and graft- or donor-related factors. Advanceddonor age and the use of immunosuppression have been postu-lated as risk factors for more rapid fibrosis following LT [3].Furthermore,theadministrationofhighdosesofglucocorticoster-oids(GCs)appearstobeassociatedwiththeseverityofHCVrecur-rence, increased mortality, and graft loss in LT recipients [3].To better understand the impact of immunosuppressive drugson HCV infection, an elegant study from Thomas Pietschmann’slaboratory investigated the effect of GC, cyclosporin A, tacroli-mus, mycophenolate sodium, basiliximab, evrolimus, and azathi-oprine on the HCV life cycle [4]. To identify virus-druginteractions, Ciesek et al. studied HCV entry, replication, andassembly in permissive Huh-7.5 hepatoma cells and primaryhuman hepatocytes using HCV pseudoparticles and infectiousvirions. Using this approach, Ciesek et al. uncovered that GCsenhance HCV entry and dissemination into hepatocytes. Prednis-olone (starting at 10–50

Cost Effectiveness of Treating Hepatitis C with Interferon and Ribivirin

Hepatitis C virus (HCV) is the leading cause of chronic liver disease in the U.S. and the leading indication for liver transplant. All current

Initial Viral Load Predicts Therapeutic Response to Consensus Interferon for Hepatitis C

Hepatitis C virus (HCV) affects 2% of the U.S. population, can progress to cirrhosis, and is the leading indication for liver transplantation. Although