Hepatitis C virus infection treatment: An era of game changer direct acting antivirals and novel treatment strategies

Crit Rev Microbiol. 2016 Aug;42(4):535-47. doi: 10.3109/1040841X.2014.970123. Epub 2014 Nov 6.

Abstract

Chronic hepatitis C virus infection and associated liver diseases represent a major health care burden all over the world. The current standard of care, i.e. peginterferon-alfa (PEG-IFNα) plus ribavirin (RBV) are associated with frequent and sometimes serious adverse effects and contraindications, which further limit their therapeutic efficacy. The approval of first and second generation HCV protease inhibitors represents a major breakthrough in the development of novel direct acting antivirals (DAAs) against different HCV genotypes and establishes a new standard of care for chronically infected HCV genotypes 1 patients. Similarly, next generation protease inhibitors and HCV RNA polymerase inhibitors have shown better pharmacokinetics and pharmacodynamics in terms of broader HCV genotypes coverage, better safety profile, fewer drug interactions and possible once daily administration than first generation direct acting antivirals. The testing of adenovirus-based vector vaccines, which escalates the innate and acquired immune responses against the most conserved regions of the HCV genome in chimpanzees and humans, may be a promising therapeutic approach against HCV infection in coming future. This review article presents up-to-date knowledge and recent developments in HCV therapeutics, insights the shortcomings of current HCV therapies and key lessons from the therapeutic potential of improved anti-HCV treatment strategies.

Keywords: Anti-HCV vaccine; HCV therapeutics; RNA polymerase inhibitors; protease inhibitors; triple and quadruple therapies.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Drug Discovery / trends
  • Drug Interactions
  • Drug-Related Side Effects and Adverse Reactions
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / pharmacokinetics
  • Protease Inhibitors / pharmacology
  • Protease Inhibitors / therapeutic use*
  • Treatment Outcome
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / isolation & purification
  • Viral Hepatitis Vaccines / immunology
  • Viral Hepatitis Vaccines / isolation & purification

Substances

  • Antiviral Agents
  • Protease Inhibitors
  • Vaccines, Synthetic
  • Viral Hepatitis Vaccines