[Treatment of hepatitis C: current status and perspectives].

The treatment of hepatitis C virus (HCV) infection has significantly improved these last two decades. For nearly 15 years, the association of pegylated interferon alfa and ribavirin (PR) has allowed a sustained virologic response (SVR), i.e., a viral cure of the infection, in 45% of genotype 1-infected patients, 65% of genotype 4-, 70% in genotype 3- and around 85% of genotype 2-infected patients. A better understanding of the HCV life-cycle has led to the development of direct-acting antiviral drugs (DAAs) targeted against viral proteins (NS3/4A protease, NS5B polymerase with nucleos(t)idic and non nucleos(t)idic inhibitors, NS5A viral replication complex). The combination of first generation protease inhibitors with PR has showed a high antiviral efficiency (75% of SVR in genotypes 1) with substantial side effects for the first generation protease inhibitors, which have obtained approval to market in 2011 (Telaprevir and Boceprevir) and recommandations of use in HCV mono-infected patients in 2012 and in HCV/HIV coinfected in 2013. Then, the combination of second generation protease inhibitors with PR has increased SVR rates from 75 to 90%, while reducing treatment duration, side effects and number of pills. Next step is now interferon and ribavirin free combination of DAAs, about to become the standard of care in 2015. These excellent results in 'easy-to-treat' patients and in small population studies has now been confirmed in phase III studies and in 'difficult-to-treat' patients (treatment - especially protease inhibitors-experienced patients, cirrhotic patients, liver and renal transplant patients, HIV co-infected patients, and subjects with polypharmacy, at increased risk of drug interaction).