Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges

Gastroenterology. 2019 Jan;156(2):431-445. doi: 10.1053/j.gastro.2018.10.024. Epub 2018 Oct 17.


Chronic infection with hepatitis C virus is a major cause of liver disease and hepatocellular carcinoma worldwide. After the discovery of hepatitis C virus 3 decades ago, the identification of the structure of the viral proteins, combined with high-throughput replicon models, enabled the discovery and development of direct-acting antivirals. These agents have revolutionized patient care, with cure rates of more than 90%. We review the status of direct-acting antiviral therapies for hepatitis C virus infection and discuss remaining challenges. We highlight licensed compounds, discuss the potential to shorten therapy even further, and review different options for treatment failure and resistance. We also provide an overview of clinical experience with generic agents and evidence for their efficacy. Finally, we discuss the need for new drugs and outline promising targets for future therapies.

Keywords: Direct-Acting Antivirals; Hepatitis C; Resistance; Treatment Failure.

Publication types

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

MeSH terms

  • Antiviral Agents / pharmacology*
  • Drug Administration Schedule
  • Drug Development*
  • Hepacivirus / drug effects*
  • Hepatitis C / drug therapy*
  • Humans
  • Sustained Virologic Response


  • Antiviral Agents