Stratégies antivirales dans l'hépatite chronique C

Resolution of three-dimensional structure of several hepatitis C virus (HCV) proteins and the development of replicative cell culture systems had let to the identification of a number of potential targets for direct acting antivirals (DAAs). Numerous families of drugs that potentially inhibit the HCV lifecycle in vitro have been discovered, and some of them have reached clinical development. Two NS3/4A proteases inhibitors, boceprevir and telaprevir, have been recently approved in Europe and the United States in 2011 in combination with pegylated interferon alpha and ribavirin for the treatment of chronic hepatitis C in both treatment-naïve and -experienced patients infected with HCV genotype 1. Sustained virological response rates were about 30 % more than those achieved with dual therapy in phases III clinical trials. A number of other DAAs are in the clinical development in combination with pegylated interferon alpha and ribavirin or with other DAAs in interferon-free regimens, with or without ribavirin. They include second-wave, first- and second-generation NS3/4A protease inhibitors, nucleos(t)ide analogue inhibitors and non-nucleoside inhibitors of the RNA-dependent RNA polymerase (RdRp), inhibitors of non-structural 5A (NS5A) and host-targeted inhibitors such as cyclophilin A inhibitors. The proof of concept that interferon-free regimen may led to HCV eradication has been recently been brought. However, the ideal interferon-free DAA combination, able to eradicate HCV infection regardless HCV genotype, remains to be found.