Towards HBV curative therapies

Liver Int. 2018 Feb;38 Suppl 1(Suppl 1):102-114. doi: 10.1111/liv.13656.

Abstract

Tremendous progress has been made over the last 2 decades to discover and develop approaches to control hepatitis B virus (HBV) infections and to prevent the development of hepatocellular carcinoma using various interferons and small molecules as antiviral agents. However, none of these agents have significant impact on eliminating HBV from infected cells. Currently the emphasis is on silencing or eliminating cccDNA, which could lead to a cure for HBV. Various approaches are being developed including the development of capsid effectors, CRISPR/Cas9, TALENS, siRNA, entry and secretion inhibitors, as well as immunological approaches. It is very likely that a combination of these modalities will need to be employed to successfully eliminate HBV or prevent virus rebound on discontinuation of therapy. In the next 5 years clinical data will emerge which will provide insight on the safety and feasibility of these approaches and if they can be applied to eradicate HBV infections globally. In this review, we summarize current treatments and we highlight and examine recent therapeutic strategies that are currently being evaluated at the preclinical and clinical stage.

Keywords: HBV cure; antiviral agents; cccDNA; immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • CRISPR-Associated Protein 9
  • CRISPR-Cas Systems
  • DNA, Circular / blood
  • DNA, Viral / blood
  • Hepatitis B / therapy*
  • Hepatitis B virus / physiology
  • Humans
  • Immunotherapy*
  • RNA, Small Interfering / genetics
  • Transcription Activator-Like Effector Nucleases
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • DNA, Circular
  • DNA, Viral
  • RNA, Small Interfering
  • CRISPR-Associated Protein 9
  • Transcription Activator-Like Effector Nucleases