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Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
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Advances in hepatitis B therapeutics.

Vicente Soriano1, Pablo Barreiro2, Edward Cachay3

  • 1UNIR Health Sciences School and Medical Center, 28040 Madrid, Porto Velho, Madrid 76801-059, Spain.

Therapeutic Advances in Infectious Disease
|October 29, 2020
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Summary

New hepatitis B virus (HBV) therapies aim for a functional cure, moving beyond lifelong suppression. Promising antivirals in development show potential for HBsAg loss, a key step towards eliminating chronic HBV infection.

Keywords:
antiviral therapybulevirtidecccDNAchronic hepatitis Bcombination therapygene editinghepatitis deltaresistance

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Area of Science:

  • Hepatology
  • Virology
  • Oncology

Background:

  • Chronic hepatitis B virus (HBV) infection affects over 250 million people globally.
  • HBV is the leading cause of hepatocellular carcinoma (HCC), resulting in nearly 1 million deaths annually.
  • Current nucleos(t)ide therapies suppress HBV DNA but rarely achieve HBsAg loss, necessitating lifelong treatment.

Purpose of the Study:

  • To review the landscape of novel antiviral therapies targeting different steps of the HBV life cycle.
  • To highlight agents in advanced clinical development and their potential to achieve a functional cure.
  • To discuss the ultimate goal of HBV therapy: virus eradication through cccDNA elimination.

Main Methods:

  • Review of clinical development pipeline for HBV antivirals.
  • Analysis of drugs targeting entry, cccDNA, translation, capsid assembly, polymerase, and secretion.
  • Evaluation of agents in advanced clinical trials, including bulevirtide, JNJ-6379, ABI-H0731, ARO-HBV, and REP-2139.

Main Results:

  • Several novel antivirals demonstrate higher potency than current therapies.
  • ARO-HBV and REP-2139 have shown significant HBsAg loss in patients.
  • Combination therapies are anticipated to enhance treatment efficacy.

Conclusions:

  • Novel antivirals offer new hope for achieving a functional cure in chronic hepatitis B.
  • HBsAg loss is a critical milestone towards sustained remission after treatment cessation.
  • Eliminating the cccDNA reservoir remains the ultimate goal for complete HBV eradication.