Emerging therapies for the treatment of hepatitis C

Abstract

Opportunities to treat infection with hepatitis C virus (HCV) are evolving rapidly. From the introduction of interferon‐α monotherapy in 1992 to the approval of telaprevir‐ and boceprevir‐based triple therapies with pegylated interferon‐α and ribavirin in 2011, the chances of curing patients infected with HCV genotype 1 have improved from <10% to approximately 70%. Significant further improvements are on the horizon, which may well cure virtually all hepatitis C patients with an all‐oral, interferon‐free regimen in the very near future. These exciting developments are reviewed in the present article.

Figure 1

Major steps of the HCV life cycle are shown schematically. HCV polyprotein procession is targeted by NS3-4A inhibitors. HCV RNA replication is targeted by NS5B polymerase inhibitors, NS5A inhibitors, and cyclophilin A inhibitors. However, HCV proteins interact throughout the HCV life cycle, and DAAs therefore impact on multiple steps in the HCV life cycle. This was shown for example for NS5A inhibitors, which affect HCV replication, assembly and release. Specific inhibitors of viral entry or assembly and release are in preclinical or early clinical development. CLDN1, claudin-1; LDL-R, low density lipoprotein receptor; SR-B1, scavenger receptor B1.