title: Emerging treatments for chronic hepatitis C.
abstract: Advances in understanding the hepatitis C virus (HCV) life cycle and the urgent need to find complementary direct-acting antiviral (DAA) therapies has led to substantial advancements in treating chronic hepatitis C. The introduction of telaprevir and boceprevir in 2011 increased the sustained virological response (SVR) rate from approximately 50% to > 70%, but this therapy further restricted patient eligibility and is only approved for treating HCV genotype 1 infection. Interferon has long remained the backbone of HCV therapy and helps prevent viral breakthrough. However, interferon has limited effectiveness and is associated with severe adverse effects and toxicity, especially among cirrhotic patients. Moving to interferon-free therapies should greatly improve SVR rates and offer new treatments for other HCV genotypes and for ineligible patients or patients failing to respond to prior therapies. However, without the relative safety of interferon to suppress viral escape, vigilance will be required to select appropriate therapies and monitor resistance. Several DAAs are currently undergoing clinical trials and will soon undergo the approval process. Goals of future HCV clinical research will be to identify combinations of DAAs with high genetic barriers, investigate optimal treatment doses and durations, and determine the role of ribavirin in DAA therapies.
authors.affiliation: Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: C Nelson
authors.initials: CN
authors.lastname: Hayes
authors.affiliation: Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; Liver Research Project Center, Hiroshima University, Hiroshima, Japan; Laboratory for Digestive Diseases, Center for Genomic Medicine, Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan. Electronic address: chayama@hiroshima-u.ac.jp.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline
keywords: NS3/4A protease inhibitor; NS5A inhibitor; NS5B RNA-dependent RNA polymerase; clinical trials; direct-acting antiviral; interferon-free therapy