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Hepatitis B Virus Cure: Targets and Future Therapies

Hye Won Lee1,2,3, Jae Seung Lee1,2,3, Sang Hoon Ahn1,2,3

  • 1Department of Internal Medicine, College of Medicine, Yonsei University, Seoul 03722, Korea.

International Journal of Molecular Sciences
|December 31, 2020
PubMed

Insights

Chronic hepatitis B virus (HBV) infection is a global health challenge. New therapies targeting covalently closed circular DNA aim to achieve HBV cure, moving beyond current treatments that rarely lead to HBsAg loss.

Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Chronic hepatitis B virus (HBV) infection poses a significant global health burden, leading to liver fibrosis, cirrhosis, and hepatocellular carcinoma.
  • Current antiviral therapies, primarily nucleos(t)ide analogues, effectively suppress HBV replication but rarely achieve hepatitis B surface antigen (HBsAg) loss or seroconversion due to incomplete targeting of the viral covalently closed circular DNA (cccDNA).

Purpose of the Study:

  • To review newly investigated therapeutic compounds and emerging treatment strategies for chronic hepatitis B.
  • To evaluate the potential of novel agents and combination therapies to achieve a functional cure for HBV infection, defined by HBsAg loss and seroconversion.

Main Methods:

  • Review of preclinical and clinical trial data for novel anti-HBV agents.
  • Analysis of therapeutic strategies targeting different stages of the HBV life cycle, including those acting on cccDNA.

Main Results:

  • Current antiviral treatments achieve viral suppression but have limited success in achieving HBsAg loss (<10% in 5 years).
  • Emerging therapies and combination regimens show promise in interrupting the HBV life cycle and increasing the rate of HBsAg seroclearance.

Conclusions:

  • Achieving a functional cure for chronic hepatitis B requires strategies that eliminate the viral cccDNA reservoir.
  • Optimized treatment regimens combining existing and novel anti-HBV agents are crucial for increasing the rates of HBsAg loss and achieving a cure.

Keywords:
curehepatitis Btargettreatment

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