Hepatitis C treatment: an incipient therapeutic revolution

Trends Mol Med. 2014 Jun;20(6):315-21. doi: 10.1016/j.molmed.2014.02.002. Epub 2014 Mar 11.


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.

Keywords: NS3–4A serine protease inhibitors; direct-acting antivirals (DAAs); hepatitis C; pegylated interferon; simeprevir; sofosbuvir.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiviral Agents / pharmacology*
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Interferon-alpha / pharmacology
  • Molecular Targeted Therapy
  • Oligopeptides / pharmacology
  • Proline / analogs & derivatives
  • Proline / pharmacology
  • Protease Inhibitors / pharmacology
  • Sofosbuvir
  • Uridine Monophosphate / analogs & derivatives
  • Uridine Monophosphate / pharmacology


  • Antiviral Agents
  • Interferon-alpha
  • Oligopeptides
  • Protease Inhibitors
  • telaprevir
  • N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
  • Proline
  • Uridine Monophosphate
  • Sofosbuvir