Hepatitis delta virus: insights into a peculiar pathogen and novel treatment options

Nat Rev Gastroenterol Hepatol. 2016 Oct;13(10):580-9. doi: 10.1038/nrgastro.2016.126. Epub 2016 Aug 18.

Abstract

Chronic hepatitis D is the most severe form of viral hepatitis, affecting ∼20 million HBV-infected people worldwide. The causative agent, hepatitis delta virus (HDV), is a unique human pathogen: it is the smallest known virus; it depends on HBV to disseminate its viroid-like RNA; it encodes only one protein (HDAg), which has both structural and regulatory functions; and it replicates using predominantly host proteins. The failure of HBV-specific nucleoside analogues to suppress the HBV helper function, and the limitations of experimental systems to study the HDV life cycle, have impeded the development of HDV-specific drugs. Thus, the only clinical regimen for HDV is IFNα, which shows some efficacy but long-term virological responses are rare. Insights into the receptor-mediated entry of HDV, and the observation that HDV assembly requires farnesyltransferase, have enabled novel therapeutic strategies to be developed. Interference with entry, for example through blockade of the HBV-HDV-specific receptor sodium/taurocholate cotransporting polypeptide NTCP by Myrcludex B, and inhibition of assembly by blockade of farnesyltransferase using lonafarnib or nucleic acid polymers such as REP 2139-Ca, have shown promising results in phase II studies. In this Review, we summarize our knowledge of HDV epidemiology, pathogenesis and molecular biology, with a particular emphasis on possible future developments.

Publication types

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

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • Cells, Cultured
  • Disease Models, Animal
  • Hepatitis D, Chronic / drug therapy*
  • Hepatitis D, Chronic / epidemiology
  • Hepatitis D, Chronic / etiology
  • Hepatitis Delta Virus / chemistry
  • Hepatitis Delta Virus / physiology
  • Hepatitis Delta Virus / ultrastructure
  • Host-Pathogen Interactions
  • Humans
  • Interferon-alpha / therapeutic use*
  • Lipopeptides / therapeutic use
  • Nucleic Acids / therapeutic use
  • Piperidines / therapeutic use
  • Pyridines / therapeutic use
  • Virus Replication / drug effects
  • Virus Replication / physiology

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Lipopeptides
  • Nucleic Acids
  • Piperidines
  • Pyridines
  • myrcludex-B
  • lonafarnib