title: New direct-acting antivirals' combination for the treatment of chronic hepatitis C.
abstract: Chronic hepatitis C is one of the leading causes of chronic liver disease, with approximately 170 million people infected worldwide. The severity of disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma (HCC). Sustained virological response (SVR) is long lasting, associated with a reduced risk of cirrhosis and HCC. In the near future, standard of care (SOC) treatment of hepatitis C virus (HCV) will include the addition of direct-acting antivirals (DAAs) with a protease inhibitor to the pegylated interferon (PEG-IFN) plus ribavirin (RBV). In HCV genotype 1 patients, promising results have been reported when the protease inhibitor telaprevir or boceprevir is added to the SOC, increasing SVR rates from less than 50% (PEG-IFN plus RBV) to 70% (in patients treated with a triple combination of PEG-IFN, RBV plus a protease inhibitor). The future management of patients with these new molecules will require good clinical practice, knowledge of indications, prediction of side effects and monitoring for antiviral resistance. Certain major medical needs are still unmet, requiring studies in special populations (human immunodeficiency virus-HCV-coinfected patients, transplanted patients, etc.) in genotype non-1 patients and in absolute non-responders. Combinations of antivirals with additive potency that lack cross resistance and with a good safety profile may provide new regimens in the future to make HCV the first chronic viral infection eradicated worldwide with a finite duration of combination DAA therapy without IFN. There is ongoing development of new molecules such as HCV enzyme inhibitors. The aim of this review is to summarize the results obtained with DAAs: protease and polymerase inhibitors.
authors.affiliation: INSERM, U773, Centre de Recherche Bichat-Beaujon CRB3, and Service d'Hépatologie, Hôpital Beaujon, Clichy, France. tarik.asselah@bjn.aphp.fr
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000378:metabolism / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000378:metabolism / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D059039:Standard of Care; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; 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; C100416:peginterferon alfa-2a