Hepatitis C treatment: an incipient therapeutic revolution

• We review the latest treatment algorithms for treating chronic hepatitis C infection.
• We explain how direct-acting antivirals (DAAs) target specific aspects of the hepatitis C virus (HCV) life cycle.
• The NS5B polymerase inhibitor, sofosbuvir, is efficacious across all HCV genotypes.
• Combining DAAs across distinct classes without requiring interferon is the next step.

An exciting paradigm shift is occurring in the treatment of hepatitis C virus (HCV). We now have the capacity to specifically target therapy to HCV proteins, and thereby directly interrupt the viral life cycle. The first direct-acting antivirals (DAAs), the NS3–4A serine protease inhibitors boceprevir and telaprevir, improved the rate of sustained virologic response (SVR), but their toxicities combined with PEG-IFN and RBV limited their overall efficacy. Sofosbuvir, a nucleotide HCV polymerase inhibitor, is now available and offers better tolerability and efficacy across all HCV genotypes. The next phase of therapy will be combining several classes of DAAs without IFN in order to make sustained clearance of hepatitis C deliverable to a much larger number of infected individuals.