Direct acting antivirals for the treatment of chronic hepatitis C: one pill a day for tomorrow.
Chronic hepatitis C is one of the leading causes of chronic liver disease with approximately 170 million people infected worldwide. Sustained virological response (SVR) is equivalent to viral eradication and associated with a reduction in the risk of cirrhosis. Nowadays the treatment for hepatitis C virus (HCV) genotype 1 chronic infection is the addition of direct acting antivirals (DAA) with a protease inhibitor (telaprevir or boceprevir) to the pegylated interferon (PEG-IFN) plus ribavirin (RBV) regimen. The future management of patients with these new molecules will require good clinical practice, knowledge of indications, management of side effects and monitoring for antiviral resistance. Certain major medical needs are still unmet and require studies in special populations (HIV-HCV coinfected patients, transplanted patients, etc.…) and also in HCV non-1 genotype patients and in non-responders. Second generation DAA are in development. 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. The aim of this review is to summarize mechanisms of action and results obtained with DAAs.
Service d'hépatologie, Hôpital Beaujon, APHP, University Paris-Diderot and INSERM CRB3, Clichy, France. tarik.asselah@bjn.aphp.fr
Tarik
T
Asselah
Patrick
P
Marcellin
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D060740:Disease Eradication; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; 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