Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Hepatitis: HELP
Articles from Goethe Universitat Frankfurt
Based on 339 articles published since 2008
||||

These are the 339 published articles about Hepatitis that originated from Goethe Universitat Frankfurt during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14
1 Guideline [Prophylaxis, diagnosis and therapy of hepatitis C virus (HCV) infection: the German guidelines on the management of HCV infection]. 2010

Sarrazin, C / Berg, T / Ross, R S / Schirmacher, P / Wedemeyer, H / Neumann, U / Schmidt, H H / Spengler, U / Wirth, S / Kessler, H H / Peck-Radosavljevic, M / Ferenci, P / Vogel, W / Moradpour, D / Heim, M / Cornberg, M / Protzer, U / Manns, M P / Fleig, W E / Dollinger, M M / Zeuzem, S. ·Medizinische Klinik I, Johann-Wolfgang-Goethe-Universität, Frankfurt am Main, Germany. ·Z Gastroenterol · Pubmed #20119896.

ABSTRACT: -- No abstract --

2 Editorial Overcoming the roadblocks in hepatitis C virus infection. 2014

Baumert, Thomas F / Zeuzem, Stefan. ·Inserm U1110, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Electronic address: Thomas.Baumert@unistra.fr. · Department of Medicine, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany. Electronic address: zeuzem@em.uni-frankfurt.de. ·J Hepatol · Pubmed #25443338.

ABSTRACT: -- No abstract --

3 Editorial [Revolution in the treatment of hepatitis C -- how to adopt the guidelines afterwards?]. 2014

Lynen Jansen, P / Kopp, I / Nothacker, M / Zeuzem, S. ·Geschäftsstelle der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten, Berlin. · AWMF Institut für Medizinisches Wissensmanagement (IMWI), Philipps-Universität Marburg. · Medizinische Klinik 1, Klinikum der Goethe-Universität, Frankfurt a. M. ·Z Gastroenterol · Pubmed #25313625.

ABSTRACT: -- No abstract --

4 Review Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH): cascade of events, clinical aspects, and pharmacotherapy options. 2018

Teschke, Rolf. ·a Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Hanau, Academic Teaching Hospital of the Medical Faculty , Goethe University Frankfurt/Main , Frankfurt/Main , Germany. ·Expert Opin Pharmacother · Pubmed #29708448.

ABSTRACT: INTRODUCTION: Clinicians caring for patients with alcoholic hepatitis (AH) are often confronted with the question of the best pharmacotherapy to be used. AREAS COVERED: This article covers metabolic aspects of alcohol as the basis of understanding pharmacotherapy and to facilitate choosing the drug therapeutic options for patients with severe AH. EXPERT OPINION: Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH) as terms are often used interchangeably in scientific literature but a stringent differentiation is recommended for proper clarity. As opposed to ASH, the clinical course of AH is often severe and requires an effective drug treatment strategy, in addition to absolute alcohol abstinence and nutritional support. Drug options include corticosteroids as a first choice and pentoxifylline, an inhibitor of phosphodiesterase, as a second line therapy, especially in patients with contraindications for a corticosteroid therapy such as infections or sepsis. At seven days under corticosteroids, treatment should be terminated in non-responders, and patients must then be evaluated for liver transplantation. Pentoxifylline is not effective as a rescue therapy for these patients. Other treatments such as infliximab, propylthiouracil, N-acetylcysteine, silymarin, colchicine, insulin and glucagon, oxandrolone, testosterone, and polyunsaturated lecithin are not effective in severe AH. For liver transplantation, few patients will be eligible.

5 Review Protease inhibitor therapy for hepatitis C virus-infection. 2018

de Leuw, P / Stephan, C. ·a Medical Clinic II, Infectious Diseases Unit , Goethe-University Hospital Frankfurt , Frankfurt am Main , Germany. ·Expert Opin Pharmacother · Pubmed #29595065.

ABSTRACT: INTRODUCTION: The hepatitis C virus (HCV) has affected an estimated of 80 million individuals worldwide and is a strain on public health. Around 25-30% of patients in Europe and the US who are infected with HIV are coinfected with HCV. Prior to 2013, treatment modalities containing an NS3/4A protease inhibitor in combination with pegylated interferon and ribavirin improved sustained virological response (SVR) rates. However, rates of severe side effects were high. Nowadays, oral direct-acting antiviral (DAA) combination therapy offers excellent treatment efficacy, safety and tolerability. AREAS COVERED: This review focuses on the current literature and clinical evidence and their impact regarding NS3/4A protease inhibitors. The pitfalls encountered in treating HIV- and HBV-coinfected patients are also discussed. EXPERT OPINION: In the era of DAA treatment, third-generation pan-genotypic NS3/4A protease inhibitors (mainly glecaprevir and voxilaprevir) show high antiviral activity and a genetic resistance barrier with cure rates of over 95% when combined with an NS5A inhibitor, irrespective of baseline resistance associated variants (RASs) being present. These new key components of DAA combination therapy are impressive options to eradicate HCV in the so-called difficult-to-treat population (e.g. compensated cirrhosis, end-stage renal disease and patients who failed previous DAA treatment).

6 Review Autoantibodies in Autoimmune Hepatitis: Can Epitopes Tell Us about the Etiology of the Disease? 2018

Christen, Urs / Hintermann, Edith. ·Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany. ·Front Immunol · Pubmed #29503645.

ABSTRACT: Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are serious autoimmune liver diseases that are characterized by a progressive destruction of the liver parenchyma and/or the hepatic bile ducts and the development of chronic fibrosis. Left untreated autoimmune liver diseases are often life-threatening, and patients require a liver transplantation to survive. Thus, an early and reliable diagnosis is paramount for the initiation of a proper therapy with immunosuppressive and/or anticholelithic drugs. Besides the analysis of liver biopsies and serum markers indicating liver damage, the screening for specific autoantibodies is an indispensable tool for the diagnosis of autoimmune liver diseases. Such liver autoantigen-specific antibodies might be involved in the disease pathogenesis, and their epitope specificity may give some insight into the etiology of the disease. Here, we will mainly focus on the generation and specificity of autoantibodies in AIH patients. In addition, we will review data from animal models that aim toward a better understanding of the origins and pathogenicity of such autoantibodies.

7 Review Hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C: a systematic review and meta-analysis. 2018

Mücke, Marcus M / Backus, Lisa I / Mücke, Victoria T / Coppola, Nicola / Preda, Carmen M / Yeh, Ming-Lun / Tang, Lydia S Y / Belperio, Pamela S / Wilson, Eleanor M / Yu, Ming-Lung / Zeuzem, Stefan / Herrmann, Eva / Vermehren, Johannes. ·Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany. · Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA. · Department of Mental Health and Public Medicine, University of Campania, Naples, Italy. · Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Bucharest, Romania. · Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. · Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. · Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA; Division of Infectious Diseases, Department of Medicine, VA Maryland Health Care System, Baltimore, MD, USA. · Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, Frankfurt am Main, Germany. · Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany. Electronic address: johannes.vermehren@kgu.de. ·Lancet Gastroenterol Hepatol · Pubmed #29371017.

ABSTRACT: BACKGROUND: Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection might pose a risk for hepatitis B virus (HBV) reactivation in patients coinfected with chronic or resolved HBV infection. The need for HBV antiviral prophylaxis during DAA treatment remains controversial. We aimed to analyse the absolute risk of HBV reactivation in patients with active or resolved HBV infection treated with DAAs for HCV infection. METHODS: For this systematic review and meta-analysis, we searched PubMed, Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and Web of Science from Oct 1, 2010, to Sept 30, 2017, to identify studies of patients with chronic or resolved HBV infection at baseline treated with DAAs for chronic HCV infection. Conference proceedings, abstract books, and references from relevant reviews were also examined for potential studies. Two independent researchers extracted data and assessed quality and risk of bias. Data were pooled by use of random-effects models. The primary outcome was HBV reactivation defined by standardised nomenclature. This study is registered with PROSPERO, number CRD42017065882. FINDINGS: We identified 17 observational studies involving 1621 patients with chronic (n=242) or resolved (n=1379) HBV infection treated with different DAAs. The pooled proportion of patients who had HBV reactivation was 24% (95% CI 19-30) in patients with chronic HBV infection and 1·4% (0·8-2·4) in those with resolved HBV infection. In patients with chronic HBV infection, the pooled proportion of patients with HBV-reactivation-related hepatitis was 9% (95% CI 5-16) and the relative risk (RR) of HBV-reactivation-related hepatitis was significantly lower in patients with HBV DNA below the lower limit of quantification at baseline than in those with quantifiable HBV DNA (RR 0·17, 95% CI 0·06-0·50; p=0·0011). Three major clinical events related to HBV reactivation in patients with chronic HBV infection were reported (one patient had liver decompensation and two had liver failure, one of whom required liver transplantation). In patients with resolved HBV infection, no HBV-reactivation-related hepatitis was reported. INTERPRETATION: HBV reactivation occurs frequently in patients with chronic HBV and HCV coinfection receiving DAA therapy but is rare among patients with resolved HBV infection. Use of antiviral prophylaxis might be warranted in patients who test positive for hepatitis B surface antigen (HBsAg), particularly those with quantifiable HBV DNA. FUNDING: None.

8 Review Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis. 2018

Herrmann, Eva / de Lédinghen, Victor / Cassinotto, Christophe / Chu, Winnie C-W / Leung, Vivian Y-F / Ferraioli, Giovanna / Filice, Carlo / Castera, Laurent / Vilgrain, Valérie / Ronot, Maxime / Dumortier, Jérôme / Guibal, Aymeric / Pol, Stanislas / Trebicka, Jonel / Jansen, Christian / Strassburg, Christian / Zheng, Rongqin / Zheng, Jian / Francque, Sven / Vanwolleghem, Thomas / Vonghia, Luisa / Manesis, Emanuel K / Zoumpoulis, Pavlos / Sporea, Ioan / Thiele, Maja / Krag, Aleksander / Cohen-Bacrie, Claude / Criton, Aline / Gay, Joel / Deffieux, Thomas / Friedrich-Rust, Mireen. ·Department of Medicine, Institute of Biostatistics and Mathematical Modelling, Goethe University Frankfurt, Frankfurt, Germany. · Hepatology Unit, Centre Hospitalier Universitaire, Bordeaux, France. · INSERM U1053, Bordeaux University, Bordeaux, France. · Department of Diagnostic and Interventional Imaging, Centre Hospitalier Universitaire du Haut-Lévèque, Bordeaux, France. · Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China. · Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. · Infectious Diseases Department, Ultrasound Unit, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. · Department of Hepatology, Assistance Publique de Hôpitaux de ParisHôpital Universitaire Beaujon, Clichy, France. · Department of Radiology, Assistance Publique de Hôpitaux de Paris, Hôpital Universitaire Beaujon, Clichy, France. · Department of Hepatology, Hospices Civils de Lyon, Hôpital Universitaire Edouard Herriot, Lyon, France. · Department of Radiology, Centre Hospitalier Général de Perpignan, Perpignan, France. · Department of Hepatology, Assistance Publique de Hôpitaux de Paris, Hôpital Cochin, and Université Paris Descartes and INSERM UMS20, Institut Pasteur, Paris, France. · Department of Internal Medicine I, Universitätsklinikum Bonn, Bonn, Germany. · Research Unit for Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark. · European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain. · Department of Medical Ultrasonics, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. · Division of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium. · Department of Internal Medicine, Athens University School of Medicine, Athens, Greece. · Department of Radiology, Athens University School of Medicine, Athens, Greece. · Department of Gastroenterology and Hepatology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania. · SuperSonic Imagine, Aix-en-Provence, France. · INSERM U979-Institut Langevin-ESPCI ParisTec, Paris, France. · Department of Internal Medicine, Goethe University Hospital Frankfurt, Frankfurt, Germany. ·Hepatology · Pubmed #28370257.

ABSTRACT: Two-dimensional shear wave elastography (2D-SWE) has proven to be efficient for the evaluation of liver fibrosis in small to moderate-sized clinical trials. We aimed at running a larger-scale meta-analysis of individual data. Centers which have worked with Aixplorer ultrasound equipment were contacted to share their data. Retrospective statistical analysis used direct and paired receiver operating characteristic and area under the receiver operating characteristic curve (AUROC) analyses, accounting for random effects. Data on both 2D-SWE and liver biopsy were available for 1,134 patients from 13 sites, as well as on successful transient elastography in 665 patients. Most patients had chronic hepatitis C (n = 379), hepatitis B (n = 400), or nonalcoholic fatty liver disease (n = 156). AUROCs of 2D-SWE in patients with hepatitis C, hepatitis B, and nonalcoholic fatty liver disease were 86.3%, 90.6%, and 85.5% for diagnosing significant fibrosis and 92.9%, 95.5%, and 91.7% for diagnosing cirrhosis, respectively. The AUROC of 2D-SWE was 0.022-0.084 (95% confidence interval) larger than the AUROC of transient elastography for diagnosing significant fibrosis (P = 0.001) and 0.003-0.034 for diagnosing cirrhosis (P = 0.022) in all patients. This difference was strongest in hepatitis B patients. CONCLUSION: 2D-SWE has good to excellent performance for the noninvasive staging of liver fibrosis in patients with hepatitis B; further prospective studies are needed for head-to-head comparison between 2D-SWE and other imaging modalities to establish disease-specific appropriate cutoff points for assessment of fibrosis stage. (Hepatology 2018;67:260-272).

9 Review Treatment Options in Hepatitis C. 2017

Zeuzem, Stefan. ·Medical Clinik I, Department of Internal Medicine, J.W. Goethe University Hospital, Frankfurt/Main. ·Dtsch Arztebl Int · Pubmed #28143635.

ABSTRACT: BACKGROUND: Among patients with chronic hepatitis C, 20-30% develop hepatic cirrhosis and its complications within 30 years. The antiviral treatment of hepatitis C, previously interferon-based, has recently become inter - feron-free, with resulting improvements in sustained virological response rates, safety, and tolerability and a shorter duration of treatment. METHODS: This review is based on relevant publications retrieved by a selective literature search, and particularly on studies and reviews concerning the course and treatment of hepatitis C. RESULTS: The available drugs for interferon-free antiviral treatment of hepatitis C include inhibitors of the RNAdependent RNA polymerase, NS3/4A protease, and NS5A protein of the hepatitis C virus (HCV), and ribavirin. Typically, two specific inhibitors are given in combination; the usual duration of treatment is 12 weeks.The antiviral drugs differ in their genotypic antiviral effectiveness and resistance barriers. The appropriate drug(s) should be chosen in consideration of the patient's hepatic and renal function and potential drug interactions. These drugs are safe and well-tolerated and result in sustained virological response rates between 90% and 100%. CONCLUSION: All patients with hepatitis C, whatever their disease stage, can derive a sustained eradication of HCV from a combination of drugs with direct antiviral activity. Viral eradication is associated with a better quality of life and with lower morbidity and mortality.

10 Review Special populations: treating hepatitis C in patients with decompensated cirrhosis and/or advanced renal impairment. 2017

Mücke, Marcus M / Mücke, Victoria T / Lange, Christian M / Zeuzem, Stefan. ·Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt a.M., Germany. ·Liver Int · Pubmed #28052635.

ABSTRACT: Direct-acting antivirals have revolutionized the treatment of hepatitis C. Sustained virological response rates of at least 95% have become common in the general population. However, along with the ageing of the HCV population, physicians face a growing group of HCV-infected patients with advanced liver and/or renal impairment. The safety and efficacy of treatment remains a clinical challenge in these patients. This review focuses on the current state of knowledge and treatment regimens in patients with decompensated cirrhosis and severe renal impairment. It shows that distinct interferon-free treatments can achieve favourable sustained virological response rates in these difficult-to-treat patients. Moreover, pitfalls and special considerations as well as new emerging challenges in an era of interferon-free regimens will be presented in this article.

11 Review Immunopathogenic Mechanisms of Autoimmune Hepatitis: How Much Do We Know from Animal Models? 2016

Christen, Urs / Hintermann, Edith. ·Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany. christen@med.uni-frankfurt.de. · Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany. hintermann@med.uni-frankfurt.de. ·Int J Mol Sci · Pubmed #27916939.

ABSTRACT: Autoimmune hepatitis (AIH) is characterized by a progressive destruction of the liver parenchyma and a chronic fibrosis. The current treatment of autoimmune hepatitis is still largely dependent on the administration of corticosteroids and cytostatic drugs. For a long time the development of novel therapeutic strategies has been hampered by a lack of understanding the basic immunopathogenic mechanisms of AIH and the absence of valid animal models. However, in the past decade, knowledge from clinical observations in AIH patients and the development of innovative animal models have led to a situation where critical factors driving the disease have been identified and alternative treatments are being evaluated. Here we will review the insight on the immunopathogenesis of AIH as gained from clinical observation and from animal models.

12 Review Concise review: Interferon-free treatment of hepatitis C virus-associated cirrhosis and liver graft infection. 2016

Weiler, Nina / Zeuzem, Stefan / Welker, Martin-Walter. ·Nina Weiler, Stefan Zeuzem, Martin-Walter Welker, Universitätsklinikum Frankfurt, Medizinische Klinik 1, 60590 Frankfurt, Germany. ·World J Gastroenterol · Pubmed #27895394.

ABSTRACT: Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to (pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response (SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte (CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis.

13 Review Diagnostics in hepatitis C: The end of response-guided therapy? 2016

Maasoumy, Benjamin / Vermehren, Johannes. ·Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Germany. · Universitätsklinikum Frankfurt, Medizinische Klinik 1, Frankfurt am Main, Germany. Electronic address: Johannes.vermehren@kgu.de. ·J Hepatol · Pubmed #27641989.

ABSTRACT: On-treatment hepatitis C virus (HCV) RNA has been used to predict response to interferon (IFN)-based therapy. The concept of response-guided treatment (RGT) was established to determine optimal treatment duration and to early identify patients not responding to futile therapies. RGT helped to improve sustained virologic response (SVR) rates and lower the rates of adverse effects. RGT was of particular importance for telaprevir- and boceprevir-based triple therapies. RGT strategies are dependent on highly sensitive and reproducible HCV RNA quantification. However, different HCV RNA assays are used in routine clinical practice and these differ significantly in their performance characteristics. The development of IFN-free therapies has fundamentally changed the role of on-treatment HCV RNA for SVR prediction. Given the high efficacy and excellent tolerability of IFN-free regimens, the interest in treatment individualization has decreased. However, shorter treatment durations may still be desirable, particularly with respect to the high costs of current IFN-free direct-acting antiviral agents (DAAs). Moreover, some difficult-to-treat patients remain, e.g., those infected with HCV genotype 3 in whom the current standard of care may not always be sufficient to achieve SVR, especially in treatment-experienced patients with cirrhosis. Here, a RGT extension may be feasible. However, current data on the predictive value of on-treatment HCV RNA are limited and have shown conflicting results. As more potent DAAs become available, the role of response prediction may diminish further. Currently, shorter treatment duration is only based on baseline HCV RNA whereas no RGT strategy is recommended for any of the approved DAA regimens available.

14 Review The Honolulu Liver Disease Cluster at the Medical Center: Its Mysteries and Challenges. 2016

Teschke, Rolf / Eickhoff, Axel. ·Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/Main, Leimenstrasse 20, D-63450 Hanau, Germany. rolf.teschke@gmx.de. · Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/Main, Leimenstrasse 20, D-63450 Hanau, Germany. Axel_Eickhoff@klinikum-hanau.de. ·Int J Mol Sci · Pubmed #27043544.

ABSTRACT: In 2013, physicians at the Honolulu Queen's Medical Center (QMC) noticed that seven liver disease patients reported the use of OxyELITE Pro (OEP), a widely consumed dietary supplement (DS). Assuming a temporal association between OEP use and disease, they argued that OEP was the cause of this mysterious cluster. Subsequent reexamination, however, has revealed that this QMC cohort is heterogeneous and not a cluster with a single agent causing a single disease. It is heterogeneous because patients used multiple DS's and drugs and because patients appeared to have suffered from multiple liver diseases: liver cirrhosis, liver failure by acetaminophen, hepatotoxicity by non-steroidal antiinflammatory drugs (NSAIDs), resolving acute viral hepatitis by hepatitis B virus (HBV), herpes simplex virus (HSV), and varicella zoster virus (VZV), and suspected hepatitis E virus (HEV). Failing to exclude these confounders and to consider more viable diagnoses, the QMC physicians may have missed specific treatment options in some of their patients. The QMC physicians unjustifiably upgraded their Roussel Uclaf Causality Assessment Method (RUCAM) causality scores so that all patients would appear to be "probable" for OEP. However, subsequent RUCAM reassessments by our group demonstrated a lack of causality for OEP in the evaluated QMC cases. The QMC's questionable approaches explain the extraordinary accumulation of suspected OEP cases at the QMC in Hawaii as single place, whereas similar cohorts were not published by any larger US liver center, substantiating that the problem is with the QMC. In this review article, we present and discuss new case data and critically evaluate upcoming developments of problematic regulatory assessments by the US Centers for Disease Control and Prevention (CDC), the Hawaii Department of Health (HDOH), and the Food and Drug Administration (FDA), as based on invalid QMC conclusions, clarifying now also basic facts and facilitating constructive discussions.

15 Review New HCV Therapies and Liver Transplantation. 2016

Werner, Jens M / Vermehren, Johannes. ·1 Department of Surgery, University Hospital Regensburg, Regensburg, Bavaria, Germany. 2 Department of Internal Medicine, University Hospital Frankfurt, Frankfurt, Germany. ·Transplantation · Pubmed #26813409.

ABSTRACT: -- No abstract --

16 Review The importance of resistance to direct antiviral drugs in HCV infection in clinical practice. 2016

Sarrazin, Christoph. ·J. W. Goethe-University Hospital, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: sarrazin@em.uni-frankfurt.de. ·J Hepatol · Pubmed #26409317.

ABSTRACT: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antiviral agents (DAA) is associated with high rates of sustained virologic response. Remaining factors associated with treatment failure include advanced stages of liver fibrosis, response to previous antiviral therapy and viral factors such as baseline viral load and suboptimal interaction of the DAA with the target based on viral variants. Heterogeneity within NS3, NS5A, and NS5B areas interacting with DAAs exist between HCV geno- and subtypes as well as HCV isolates of the same geno- and subtype and amino acid polymorphisms associated with suboptimal efficacy of DAAs are termed resistance-associated variants (RAVs). RAVs may be associated with virologic treatment failure. However, virologic treatment failure typically occurs only if other negative predictive host or viral factors are present at the same time, susceptibility to additional antiviral agents is reduced or duration of treatment is suboptimal. In this review geno- and phenotypic resistance testing as well as clinical data on the importance of RAVs for conventional triple therapies with sofosbuvir, simeprevir, and daclatasvir and available interferon-free DAA combinations are discussed.

17 Review Hepatitis C Virus: A European Perspective. 2015

Dultz, Georg / Zeuzem, Stefan. ·Department of Medicine 1, Goethe University Hospital, Theodor-Stern-Kai 7, Frankfurt 60590, Germany. · Department of Medicine 1, Goethe University Hospital, Theodor-Stern-Kai 7, Frankfurt 60590, Germany. Electronic address: zeuzem@em.uni-frankfurt.de. ·Gastroenterol Clin North Am · Pubmed #26600221.

ABSTRACT: Chronic hepatitis C virus (HCV) infection is a major public health burden in Europe, being one of the leading causes of chronic liver disease, liver cirrhosis, and hepatocellular carcinoma. Properties of the HCV disease burden are heterogeneous across the European continent, with differences in incidence, prevalence, diagnosis and treatment rates, transmission routes, and genotype distribution. Recent estimates expect an increase in HCV-related morbidity and mortality in most European countries until 2030 even when current treatment options are taken into account. The European perspective on hepatitis C virus infection is summarized herein.

18 Review Development of sofosbuvir for the treatment of hepatitis C virus infection. 2015

Lawitz, Eric / Jacobson, Ira M / Nelson, David R / Zeuzem, Stefan / Sulkowski, Mark S / Esteban, Rafael / Brainard, Diana / McNally, John / Symonds, William T / McHutchison, John G / Dieterich, Douglas / Gane, Edward. ·Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas. · Icahn School of Medicine at Mount Sinai, New York, New York. · University of Florida, Gainesville, Florida. · Medical Center, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. · Johns Hopkins University School of Medicine, Baltimore, Maryland. · Hospital Universitario Val d'Hebron, Barcelona, Spain. · Gilead Sciences, Foster City, California. · Mount Sinai School of Medicine, New York, New York. · Auckland City Hospital, Auckland, New Zealand. ·Ann N Y Acad Sci · Pubmed #26235748.

ABSTRACT: The nucleotide analog NS5B polymerase inhibitor sofosbuvir was approved by the U.S. Food and Drug Administration (FDA) in December 2013 for the treatment of chronic hepatitis C virus (HCV) infection in combination with ribavirin or peginterferon and ribavirin. Sofosbuvir was developed to meet an urgent medical need for shorter, safer, simplified, more effective HCV treatment regimens and to reduce or eliminate the need for peginterferon. New treatment regimens were especially required for patient populations with limited treatment options, including patients who had failed prior HCV therapy, those with compensated and decompensated cirrhosis, and those who were either intolerant of or had contraindications to interferon. Sofosbuvir plus ribavirin for patients with genotype 2 or 3 HCV infection was the first approved all-oral treatment option. Sofosbuvir is also the backbone of the first regimen available for patients awaiting liver transplantation to prevent HCV recurrence, as well as the first oral interferon-free regimen for patients coinfected with HCV and HIV. This paper describes the development of sofosbuvir up to its original FDA approval.

19 Review From non-A, non-B hepatitis to hepatitis C virus cure. 2015

Pawlotsky, Jean-Michel / Feld, Jordan J / Zeuzem, Stefan / Hoofnagle, Jay H. ·National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France. Electronic address: jean-michel.pawlotsky@hmn.aphp.fr. · Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada. · Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany. · Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States. ·J Hepatol · Pubmed #25920094.

ABSTRACT: The hepatitis C virus (HCV) was discovered in the late 1980s. Interferon (IFN)-α was proposed as an antiviral treatment for chronic hepatitis C at about the same time. Successive improvements in IFN-α-based therapy (dose finding, pegylation, addition of ribavirin) increased the rates of sustained virologic response, i.e. the rates of curing HCV infection. These rates were further improved by adding the first available direct-acting antiviral (DAA) drugs to the combination of pegylated IFN-α and ribavirin. An IFN-free era finally started in 2014, yielding rates of sustained virologic response over 90% in patients treated for 8 to 24 weeks with all-oral regimens. Major challenges however remain in implementation of these new treatment strategies, not only in low- to middle-income countries, but also in high-income countries where the price of these therapies is still prohibitive. Elimination of HCV infection through treatment in certain areas is possible but raises major public health issues.

20 Review An Update on Animal Models of Autoimmune Hepatitis: Are we There Yet? 2015

Christen, Urs / Hintermann, Edith. ·Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe Universitat, Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany. christen@med.uni-frankfurt.de. ·Curr Pharm Des · Pubmed #25777755.

ABSTRACT: Autoimmune hepatitis is characterized by a progressive destruction of the liver parenchyma and a chronic fibrosis. Although the major targets of this autoimmune-mediated disease have been identified more than two decades ago, the current treatment of autoimmune hepatitis is still based on traditional therapies including a glucocorticoid treatment. One reason for this impasse is the limited availability of reliable animal models that reflect the clinical features of autoimmune hepatitis and allow for the identification of critical factors driving the autoimmune destruction and the evaluation of innovative therapies. However, the status of the liver as an immune privileged organ harbouring many immunosuppressing mechanisms hampers the development of such models. Here we will review the past and present attempts to develop a consistent animal model for autoimmune hepatitis.

21 Review Interferon-free antiviral combination therapies without nucleosidic polymerase inhibitors. 2014

Welzel, Tania Mara / Dultz, Georg / Zeuzem, Stefan. ·Department of Medicine 1, Johann Wolfgang Goethe-University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. · Department of Medicine 1, Johann Wolfgang Goethe-University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: zeuzem@em.uni-frankfurt.de. ·J Hepatol · Pubmed #25443350.

ABSTRACT: The establishment of robust HCV cell culture systems and characterization of the viral life cycle provided the molecular basis for highly innovative, successful years in HCV drug development. With the identification of direct-acting antiviral agents (DAAs), such as NS3/4A protease inhibitors, NS5A replication complex inhibitors, nucleotide and non-nucleoside polymerase inhibitors, as well as host cell targeting agents, novel therapeutic strategies were established and competitively entered clinical testing. The first-in-class NS3/4A protease inhibitors telaprevir and boceprevir, approved in 2011, were recently outpaced by the pan-genotypic nucleotide polymerase inhibitor sofosbuvir that in combination with pegylated interferon and ribavirin, further shortens therapy durations and also offers the first interferon-free HCV treatment option. In the challenging race towards the goal of interferon-free HCV therapies, however, several oral DAA regimens without nucleotide polymerase inhibitors that combine a NS3/4A protease inhibitor, a NS5A inhibitor and/or a non-nucleoside polymerase inhibitor yielded competitive results. Second generation NS3/4A protease and NS5A inhibitors promise an improved genotypic coverage and a high resistance barrier. Results of novel DAA combination therapies without the backbone of a nucleotide polymerase inhibitor, as well as treatment strategies involving host targeting agents are reviewed herein.

22 Review Decade in review-HCV: hepatitis C therapy-a fast and competitive race. 2014

Zeuzem, Stefan. ·Department of Medicine, J. W. Goethe University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. ·Nat Rev Gastroenterol Hepatol · Pubmed #25223875.

ABSTRACT: -- No abstract --

23 Review Vitamin D level and sustained virologic response to interferon-based antiviral therapy in chronic hepatitis C: a systematic review and meta-analysis. 2014

Kitson, Matthew T / Sarrazin, Christoph / Toniutto, Pierluigi / Eslick, Guy D / Roberts, Stuart K. ·Department of Gastroenterology, Alfred Hospital, Melbourne, Australia; Department of Gastroenterology, Monash University, Melbourne, Australia. · Department of Gastroenterology & Hepatology, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany. · Department of Medicine, University of Udine, Udine, Italy. · Department of Surgery, University of Sydney, Sydney, Australia. · Department of Gastroenterology, Alfred Hospital, Melbourne, Australia; Department of Gastroenterology, Monash University, Melbourne, Australia. Electronic address: s.roberts@alfred.org.au. ·J Hepatol · Pubmed #25135863.

ABSTRACT: BACKGROUND & AIMS: The baseline 25-hydroxyvitamin D (25[OH]D) level has recently been reported to be an independent predictor of sustained virologic response (SVR) to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV) for chronic hepatitis C virus (HCV) infection. However, studies have yielded inconsistent results. Thus, we conducted a systematic review and meta-analysis to clarify any association between baseline 25(OH)D level and SVR in HCV therapy. METHODS: Two reviewers searched four electronic databases (Medline, Embase, PubMed, and Cochrane trials register) and relevant international conference proceedings up to March 2014 for studies treating chronic HCV infection with PEG-IFN plus RBV where baseline 25(OH)D level was tested. Studies involving patients with HIV co-infection, previous liver transplantation or those receiving vitamin D supplementation were excluded. The mean baseline 25(OH)D level was compared between those who achieved and those who failed to achieve SVR. Pooled standard difference in mean 25(OH)D level, odds ratios (OR) and 95% confidence intervals (CI) were calculated with the Comprehensive Meta-Analysis software (version 2.0) using a random effects model. RESULTS: 11 studies comprising 2605 patients were included in the meta-analysis. There was no significant association between the baseline mean 25(OH)D level and SVR (OR 1.44, 95% CI 0.92-2.26; p=0.11), either in patients infected with genotypes 1/4/5 (OR 1.48, 95% CI 0.94-2.34; p=0.09) or genotypes 2/3 (OR 1.51, 95% CI 0.26-8.87; p=0.65). CONCLUSIONS: The baseline 25(OH)D level is not associated with SVR to PEG-IFN plus RBV therapy in chronic HCV infection, regardless of genotype. Any effect of vitamin D supplementation on SVR is yet to be definitively determined.

24 Review Pathogen infection as a possible cause for autoimmune hepatitis. 2014

Christen, Urs / Hintermann, Edith. ·Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital , Frankfurt am Main , Germany. ·Int Rev Immunol · Pubmed #24911790.

ABSTRACT: Autoimmune disorders afflicting the liver comprise the bona fide autoimmune diseases, primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis as well as drug-induced autoimmune-like diseases, such as halothane hepatitis. Whereas drug-induced forms of acute or chronic hepatitis often have a clear triggering factor, the etiology of classical autoimmune liver diseases is only poorly understood. Besides a genetic component present in disease susceptible individuals, environmental triggering factors are likely to play a role in the initiation and/or propagation of the disease. In this article, we will review on current evidence obtained from epidemiological associations, case studies, and findings in animal models for pathogens, to be involved in the etiology of autoimmune liver disease with a special focus on autoimmune hepatitis.

25 Review Interferon-free strategies without a nucleoside/nucleotide analogue. 2014

Welzel, Tania Mara / Zeuzem, Stefan. ·Department of Medicine 1, JW Goethe University Hospital, Frankfurt am Main, Germany. ·Semin Liver Dis · Pubmed #24782258.

ABSTRACT: The identification of viral and host factors involved in hepatitis C virus (HCV) replication was a key prerequisite for the discovery and further exploration of antiviral drug targets. As of today, numerous direct-acting antiviral agents (DAAs), as well as host-targeting agents (HTAs), have been developed and entered clinical testing. The goal to omit pegylated interferon due to its unfavorable side-effect profile from novel HCV therapeutic approaches led to an expedited design and competitive conduct of DAA combination trials striving for easily applicable, all-oral HCV treatments. Approval of several interferon-free regimens is awaited in the near future (2014/2015). Results of different DAA combination trials (without nucleos(t)ide polymerase inhibitors) and trials involving HTAs are reviewed herein.

Next