An overview of emerging therapies for the treatment of chronic hepatitis C

Med Clin North Am. 2014 Jan;98(1):17-38. doi: 10.1016/j.mcna.2013.10.011.

Abstract

Advances in our understanding of the HCV lifecycle and refinement of in vitro methods to select candidate compounds with anti-HCV activity have led to development of DAA agents and other novel antiviral therapies capable of increasing the curative SVR rates in patients with CHC. The use of the liner protease inhibitors telaprevir and boceprevir, in combination with Peg-IFN-a and ribavirin has become the new SOC for treatment of CHC genotype 1. Rapid development of new protease inhibitors, NI and NNI NS5B polymerase inhibitors, NS5A inhibitors, Peg-IFN-l, cyclophilin inhibitors, caspase inhibitors, and therapeutic vaccines promises to provide even safer and more effective therapy. Combination therapies with 2 or more oral agents may permit elimination of Peg-IFN-a in the near future. Introduction of DAA therapies will confront physicians and patients with regimens of increased complexity, a greater need for compliance, and the necessity of monitoring for virological resistance. Patients with CHC should continue to consider participation in clinical trials of new therapies to accelerate progress.

Keywords: Boceprevir; Chronic hepatitis C; Cyclophilin inhibitors; Direct-acting antivirals; Polymerase inhibitors; Protease inhibitors; Telaprevir; Therapeutic vaccines.

Publication types

  • Review

MeSH terms

  • Antiviral Agents* / classification
  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • Clinical Trials as Topic
  • Drug Therapy, Combination / methods
  • Hepacivirus* / drug effects
  • Hepacivirus* / physiology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / therapeutic use
  • Metabolic Networks and Pathways / drug effects
  • Metabolic Networks and Pathways / physiology
  • Oligopeptides / therapeutic use
  • Pharmacogenetics
  • Proline / analogs & derivatives
  • Proline / therapeutic use
  • Therapies, Investigational / methods
  • Viral Hepatitis Vaccines / therapeutic use
  • Virus Physiological Phenomena / drug effects*
  • Virus Physiological Phenomena / genetics

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Oligopeptides
  • Viral Hepatitis Vaccines
  • 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