New treatments for chronic hepatitis C virus infection

Abstract

Treatment of hepatitis C virus (HCV) infection by the combination of pegylated interferon and ribavirin has been the standard of care since 1998 and has helped to achieve a sustained virologic response (SVR) in more than 50% of patients with chronic infection. SVR represents a complete recovery from the infection, but more than 50% of genotype-1-infected patients do not achieve SVR. Progress in the understanding of the viral cycle and the characterization of the viral enzymes which are possible targets have resulted in the development of new molecules including direct-acting antivirals targeted against HCV with specificity for either genotype-1 (protease inhibitors NS3/NS4A) or wider spectrum (NS5A inhibitors, polymerase inhibitors NS5B or entry inhibitors), and nonspecific antivirals (new interferons, cyclophilin inhibitors). We review the results of phase III trials, which have clearly shown a 20% to 30% increase in the SVR rate of genotype-1-infected patients, both naive and who have received previous treatments. These new drugs have been approved at the end of 2011, after an early compassionate access to cirrhotic patients who have experienced a previous relapse or partial response to the combination therapy. In the future, the main limitations of the triple therapy will be safety against adverse effects (including skin rash and anemia, which may be easily controlled), cost, adherence, viral resistances, and drug-drug interactions that we have to avoid by therapeutic education of patients and physicians.