The evolution of the therapeutic strategy in hepatitis C: features of sofosbuvir and indications.

The treatment of chronic hepatitis C virus infection is rapidly evolving with the entry into the therapeutic armamentarium of a series of new and highly effective direct antiviral agents, targeted to the different virus structures involved in hepatitis C virus replication and assembly. Sofosbuvir is considered, without controversies, the most promising single direct antiviral agent in the current scenario. The pharmacological properties of sofosbuvir allow a single oral daily administration and ensure a favourable drug-drug interaction profile, compared to other direct antiviral agents. Clinical development of sofosbuvir has been conducted with the strategy of positioning it as the backbone drug of several combination regimes, including triple therapy with pegylated interferon and ribavirin, but also IFN-free regimen with ribavirin alone as well as with complementary direct antiviral agents directed against other virus targets. Based on available data and International guidelines sofosbuvir is indicated in combination with pegylated interferon and ribavirin in patients infected with hepatitis C virus 1 to 6 that can take interferon, and this regimen is particularly efficacious in those who have not received any previous antiviral treatment. The pangenotypic activity, excellent safety (even in advanced liver disease) make sofosbuvir the ideal backbone for combination therapy in all hepatitis C virus patients subgroups, the limiting factors being safety and tolerability of the combined direct antiviral agent rather than those of sofosbuvir itself.