title: Is there sufficient evidence to recommend antiviral therapy in hepatitis C?
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.
authors: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: a.vandermeer@erasmusmc.nl.
authors: Adriaan J
authors: AJ
authors: van der Meer
authors: Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany.
authors: Heiner
authors: H
authors: Wedemeyer
authors: Liver Centre, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors: Jordan J
authors: JJ
authors: Feld
authors: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Bettina E
authors: BE
authors: Hansen
authors: Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany; Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors: Michael P
authors: MP
authors: Manns
authors: Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors: S
authors: S
authors: Zeuzem
authors: 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.
authors: Harry L A
authors: HL
authors: Janssen
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic
chemical_list: D000998:Antiviral Agents; D007372:Interferons
keywords: Antiviral therapy; CI; Chronic hepatitis C; Clinical efficacy; HALT-C; HCC; HCV; HR; HVPG; Hepatitis C Antiviral Long-term Treatment Against Cirrhosis; MELD; Model for End-stage Liver Disease; Mortality; OR; RCT; SVR; confidence interval; hazard ratio; hepatic venous pressure gradient; hepatitis C virus; hepatocellular carcinoma; odds ratio; randomized controlled trial; sustained virological response