Current therapy for chronic hepatitis C: The role of direct-acting antivirals

Antiviral Res. 2017 Jun;142:83-122. doi: 10.1016/j.antiviral.2017.02.014. Epub 2017 Feb 24.

Abstract

One of the most exciting developments in antiviral research has been the discovery of the direct-acting antivirals (DAAs) that effectively cure chronic hepatitis C virus (HCV) infections. Based on more than 100 clinical trials and real-world studies, we provide a comprehensive overview of FDA-approved therapies and newly discovered anti-HCV agents with a special focus on drug efficacy, mechanisms of action, and safety. We show that HCV drug development has advanced in multiple aspects: (i) interferon-based regimens were replaced by interferon-free regimens; (ii) genotype-specific drugs evolved to drugs for all HCV genotypes; (iii) therapies based upon multiple pills per day were simplified to a single pill per day; (iv) drug potency increased from moderate (∼60%) to high (>90%) levels of sustained virologic responses; (v) treatment durations were shortened from 48 to 12 or 8 weeks; and (vi) therapies could be administered orally regardless of prior treatment history and cirrhotic status. However, despite these remarkable achievements made in HCV drug discovery, challenges remain in the management of difficult-to-treat patients.

Keywords: Direct-acting antivirals; NS3/4A drugs; NS5A drugs; NS5B drugs.

Publication types

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

MeSH terms

  • Antiviral Agents / administration & dosage
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Drug Discovery
  • Drug Therapy, Combination
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferons
  • Serine Proteases / chemistry
  • Serine Proteases / drug effects
  • Time Factors
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / drug effects
  • Viral Proteins / chemistry
  • Viral Proteins / drug effects

Substances

  • Antiviral Agents
  • NS-5 protein, hepatitis C virus
  • Viral Nonstructural Proteins
  • Viral Proteins
  • Interferons
  • NS3-4A serine protease, Hepatitis C virus
  • Serine Proteases