title: Hepatitis C treatment: an incipient therapeutic revolution.
abstract: An exciting paradigm shift is occurring in the treatment of hepatitis C virus (HCV). We now have the capacity to specifically target therapy to HCV proteins, and thereby directly interrupt the viral life cycle. The first direct-acting antivirals (DAAs), the NS3-4A serine protease inhibitors boceprevir and telaprevir, improved the rate of sustained virologic response (SVR), but their toxicities combined with PEG-IFN and RBV limited their overall efficacy. Sofosbuvir, a nucleotide HCV polymerase inhibitor, is now available and offers better tolerability and efficacy across all HCV genotypes. The next phase of therapy will be combining several classes of DAAs without IFN in order to make sustained clearance of hepatitis C deliverable to a much larger number of infected individuals.
authors.affiliation: Department of Medicine, Center for Liver Diseases and Transplantation, Carolinas Medical Center, Charlotte, NC 28203, USA. Electronic address: andrew.delemos@carolinas.org.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: deLemos
authors.affiliation: Department of Medicine, Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: rtchung@partners.org.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D009842:Oligopeptides / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; 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; D014542:Uridine Monophosphate; D000069474:Sofosbuvir
keywords: NS3–4A serine protease inhibitors; direct-acting antivirals (DAAs); hepatitis C; pegylated interferon; simeprevir; sofosbuvir