Antiviral treatment of hepatitis C

BMJ. 2014 Jul 7;348:g3308. doi: 10.1136/bmj.g3308.

Abstract

Hepatitis C virus (HCV) infection is a substantial health problem worldwide. Most patients infected with HCV remain chronically infected, with an increased risk of cirrhosis and hepatocellular carcinoma. Although they are associated with toxicities and low sustained viral response rates, interferon alfa and ribavirin have been the mainstay of treatment until recently. New direct acting antivirals, specifically designed to inhibit three viral proteins (the NS3/4A protease, the NS5A protein, and the NS5B RNA dependent RNA polymerase) are now becoming available. The NS3/4A inhibitor simeprevir and NS5B inhibitor sofosbuvir have recently been licensed and can reduce the length of antiviral treatment, improve response rates, and allow for interferon-free regimens for some HCV genotypes. Several other newer direct acting antivirals have shown promise in clinical studies and are likely to be licensed soon. These agents seem to facilitate the use of shortened courses of combination interferon-free therapy, which are associated with high (>95%) sustained response rates and relatively few toxicities. These regimens have also been successful in patients who were previously difficult to treat, including those with cirrhosis, HIV coinfection, and those who have undergone liver transplantation. The high cost of these agents may be the biggest challenge to their implementation worldwide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Hepacivirus / genetics
  • Hepatitis C / drug therapy*
  • Hepatitis C / epidemiology
  • Hepatitis C / virology
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Polyethylene Glycols / therapeutic use
  • Protease Inhibitors / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Simeprevir
  • Sofosbuvir
  • Sulfonamides / therapeutic use
  • Uridine Monophosphate / analogs & derivatives
  • Uridine Monophosphate / therapeutic use
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Heterocyclic Compounds, 3-Ring
  • Interferon alpha-2
  • Interferon-alpha
  • NS-5 protein, hepatitis C virus
  • NS3 protein, hepatitis C virus
  • Protease Inhibitors
  • Recombinant Proteins
  • Sulfonamides
  • Viral Nonstructural Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Simeprevir
  • Uridine Monophosphate
  • peginterferon alfa-2b
  • peginterferon alfa-2a
  • Sofosbuvir