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Hepatitis: HELP
Articles by Stephan Zeuzem
Based on 328 articles published since 2009
(Why 328 articles?)

Between 2009 and 2019, S. Zeuzem wrote the following 328 articles about Hepatitis.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14
1 Guideline [Joint opinion of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the German Society for Internal Medicine (DGIM) to Daclatasvir-benefit assessment according to § 35a SGB V the G-BA]. 2015

Wedemeyer, Heiner / Zeuzem, Stefan / Manns, Michael P / Anonymous2330825 / Anonymous2340825. · ·Z Gastroenterol · Pubmed #25821867.

ABSTRACT: -- No abstract --

2 Guideline [Joint Statement of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the German Society for Internal Medicine (DGIM) to Simeprevir-benefit assessment according to § 35a SGB V the Federal Joint Committee]. 2014

Sarrazin, Christoph / Zeuzem, Stefan / Manns, Michael P / Anonymous6530818. · ·Z Gastroenterol · Pubmed #25621364.

ABSTRACT: -- No abstract --

3 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 --

4 Editorial Editorial: HBsAg serum levels in HBeAg-negative chronic HBV infection-is it a matter of genotype? Authors' reply. 2018

Kuhnhenn, L / Jiang, B / Kubesch, A / Zeuzem, S / Sarrazin, C / Hildt, E / Peiffer, K-H. ·Department of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany. · Division of Virology, Paul Ehrlich Institute, Langen, Germany. · Department of Gastroenterology, St. Josefs Hospital, Wiesbaden, Germany. · German Center for Infection Research (DZIF), Gießen-Marburg-Langen, Germany. ·Aliment Pharmacol Ther · Pubmed #29882986.

ABSTRACT: -- No abstract --

5 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 --

6 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 --

7 Editorial [Editorial: Pharmazie in unserer Zeit 1/2011]. 2011

Dingermann, Theo / Zeuzem, Stefan. · ·Pharm Unserer Zeit · Pubmed #21194071.

ABSTRACT: -- No abstract --

8 Editorial Do differences in pegylation of interferon alfa matter? 2010

Zeuzem, Stefan. · ·Gastroenterology · Pubmed #19932662.

ABSTRACT: -- No abstract --

9 Editorial Forewarned is forearmed. 2009

Zeuzem, Stefan. · ·J Hepatol · Pubmed #19660821.

ABSTRACT: -- No abstract --

10 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.

11 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.

12 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.

13 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.

14 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.

15 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.

16 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.

17 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.

18 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 --

19 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.

20 Review Emerging therapies for the treatment of hepatitis C. 2014

Lange, Christian M / Jacobson, Ira M / Rice, Charles M / Zeuzem, Stefan. · ·EMBO Mol Med · Pubmed #24106239.

ABSTRACT: Opportunities to treat infection with hepatitis C virus (HCV) are evolving rapidly. From the introduction of interferon‐α monotherapy in 1992 to the approval of telaprevir‐ and boceprevir‐based triple therapies with pegylated interferon‐α and ribavirin in 2011, the chances of curing patients infected with HCV genotype 1 have improved from <10% to approximately 70%. Significant further improvements are on the horizon, which may well cure virtually all hepatitis C patients with an all‐oral, interferon‐free regimen in the very near future. These exciting developments are reviewed in the present article.

21 Review Is there sufficient evidence to recommend antiviral therapy in hepatitis C? 2014

van der Meer, Adriaan J / Wedemeyer, Heiner / Feld, Jordan J / Hansen, Bettina E / Manns, Michael P / Zeuzem, S / Janssen, Harry L A. ·Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: a.vandermeer@erasmusmc.nl. · Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany. · Liver Centre, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. · Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany; Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany. · Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany. · Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Liver Centre, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. ·J Hepatol · Pubmed #23973931.

ABSTRACT: While patients with chronic hepatitis C virus (HCV) infection are treated in order to prevent liver-related morbidity and mortality, we rely on sustained virological response (SVR) as a virological biomarker to evaluate treatment efficacy in both clinical practice as well as in drug development. However, conclusive evidence for the clinical benefit of antiviral therapy or validity of SVR as surrogate marker, as derived from trials randomizing patients to a treatment or control arm, is lacking. In fact, the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial recently showed an increased mortality rate among interferon-treated patients compared to untreated controls. Consequently, the recommendation to treat patients with chronic HCV infection was challenged. Here, we argue that the possible harmful effect of long-term low-dose pegylated interferon mono therapy, as was observed in the HALT-C trial cohort, cannot be extrapolated to potentially curative short-term treatment regimens. Furthermore, we discuss SVR as a surrogate biomarker, based on numerous studies which indicated an association between SVR and improvements in health-related quality of life, hepatic inflammation and fibrosis, and portal pressure as well as a reduced risk for hepatocellular carcinoma (HCC), liver failure and mortality.

22 Review The new paradigm of hepatitis C therapy: integration of oral therapies into best practices. 2013

Afdhal, N H / Zeuzem, S / Schooley, R T / Thomas, D L / Ward, J W / Litwin, A H / Razavi, H / Castera, L / Poynard, T / Muir, A / Mehta, S H / Dee, L / Graham, C / Church, D R / Talal, A H / Sulkowski, M S / Jacobson, I M / Anonymous4430773. ·Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. ·J Viral Hepat · Pubmed #24168254.

ABSTRACT: Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.

23 Review Hepatitis C-associated B-cell non-Hodgkin lymphomas. Epidemiology, molecular signature and clinical management. 2013

Peveling-Oberhag, Jan / Arcaini, Luca / Hansmann, Martin-Leo / Zeuzem, Stefan. ·Department of Internal Medicine 1, J.W. Goethe-University Hospital, Frankfurt, Germany. jan.peveling-oberhag@kgu.de ·J Hepatol · Pubmed #23542089.

ABSTRACT: There is ample epidemiologic evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin lymphoma (B-NHL). B-NHL subtypes most frequently associated with HCV are marginal zone lymphoma and diffuse large B-cell lymphoma. The most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). In fact, for indolent HCV-associated B-NHL, first-line AVT instead of standard immune-chemotherapy might be considered. Molecular mechanisms of HCV-NHL development are still poorly understood. Three general theories have emerged to understand the HCV-induced lymphomagenesis: (1) continuous external stimulation of lymphocyte receptors by viral antigens and consecutive proliferation; (2) HCV replication in B cells with oncogenic effect mediated by intracellular viral proteins; (3) permanent B-cell damage, e.g., mutation of tumor suppressor genes, caused by a transiently intracellular virus ("hit and run" theory). This review systematically summarizes the data on epidemiology, interventional studies, and molecular mechanisms of HCV-associated B-NHL.

24 Review New therapeutic strategies in HCV: polymerase inhibitors. 2013

Gerber, Ludmila / Welzel, Tania M / Zeuzem, Stefan. ·Klinikum der J.W. Goethe Universität, Frankfurt am Main, Germany. ·Liver Int · Pubmed #23286851.

ABSTRACT: The characterization of the viral life cycle facilitated the development of directly acting antiviral drugs. Among those, several inhibitors of the viral RNA-dependent RNA polymerase have proven effectiveness in clinical trials. The characteristics of different nucleos(t)ide and non-nucleoside polymerase inhibitors, as well as their clinical applications and combinations with other classes of directly acting antiviral drugs are reviewed herein.

25 Review Clinical management of drug-drug interactions in HCV therapy: challenges and solutions. 2013

Burger, David / Back, David / Buggisch, Peter / Buti, Maria / Craxí, Antonio / Foster, Graham / Klinker, Hartwig / Larrey, Dominique / Nikitin, Igor / Pol, Stanislas / Puoti, Massimo / Romero-Gómez, Manuel / Wedemeyer, Heiner / Zeuzem, Stefan. ·Department of Pharmacy, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. D.Burger@akf.umcn.nl ·J Hepatol · Pubmed #23137766.

ABSTRACT: Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals telaprevir and boceprevir, which are both substrates and inhibitors of the cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug-drug interactions have become a cornerstone in the evaluation of patients starting and continuing HCV combination therapy. In our opinion, an overview of conducted drug-drug interaction studies and a list of contraindicated medications is not enough for the clinical management of these drug-drug interactions. Knowledge of pharmacokinetic profiles and concentration-effect relationships is key for the interpretation of these data, and insight into how to manage these interactions (e.g., dose adjustments, safe alternatives and therapeutic drug monitoring) is of equal importance. This review provides a practical overview of the safe and effective management of these clinical challenges.