Overview of hepatitis C infection, molecular biology, and new treatment

J Infect Public Health. 2020 May;13(5):773-783. doi: 10.1016/j.jiph.2019.11.015. Epub 2019 Dec 20.

Abstract

The World Health Organization estimates that 71 million people worldwide have chronic hepatitis C viral infection. A major challenge is overall lack of public awareness of hepatitis C, particularly among infected people of their infection status. Chronic hepatitis C infection is associated with advanced liver disease, is the main cause of hepatocellular carcinoma and causes many extra-hepatic manifestations. The existence of seven viral genotypes complicates targeting of treatment. Recent years have seen the approval of many direct acting antivirals targeted at hepatitis C virus non-structural proteins. These have revolutionized therapy as they allow achievement of extremely high sustained virologic responses. Of great significance is the development of pan-genotypic drug combinations, including the NS3/4A-NS5A inhibitor combinations sofosbuvir-velpatasvir and glecaprevir-pibrentasvir. However, resistance-associated mutations can result in failure of these treatments in a small number of patients. This, combined with the high costs of treatment, highlights the importance of continued research into effective anti-hepatitis C therapies, for example aimed at viral entry. Recent developments include identification of the potential of low-cost anti-histamines for repurposing as inhibitors of hepatitis C viral entry. In this review we focus on molecular biology of hepatitis C virus, and the new developments in hepatitis C treatment.

Keywords: Direct-acting antiviral; Hepatitis; NS5A; Resistance-associated variant; Sofosbuvir.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / therapeutic use
  • Carbamates / therapeutic use
  • Drug Combinations
  • Drug Resistance, Viral / genetics
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C / drug therapy*
  • Hepatitis C / epidemiology
  • Hepatitis C / genetics
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / epidemiology
  • Hepatitis C, Chronic / genetics
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use
  • Humans
  • Pyrrolidines / therapeutic use
  • Quinoxalines / therapeutic use
  • Sofosbuvir / therapeutic use
  • Sulfonamides / therapeutic use
  • Sustained Virologic Response
  • Viral Nonstructural Proteins / genetics

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Carbamates
  • Drug Combinations
  • Heterocyclic Compounds, 4 or More Rings
  • Pyrrolidines
  • Quinoxalines
  • Sulfonamides
  • Viral Nonstructural Proteins
  • glecaprevir and pibrentasvir
  • sofosbuvir-velpatasvir drug combination
  • NS-5 protein, hepatitis C virus
  • Sofosbuvir