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Toward a Functional Cure for Hepatitis B.

Anna S F Lok1

  • 1Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.

Gut and Liver
|March 27, 2024
PubMed
Summary
This summary is machine-generated.

Achieving a functional cure for chronic hepatitis B virus (HBV) infection requires new therapies. Combinations of direct-acting antivirals and immune modulators, especially with pegylated interferon-alfa (pegIFN-α), show promise for HBsAg loss.

Keywords:
Direct-acting antiviralsHepatitis B surface antigen lossImmune modulatory therapiesNucleos(t)ide analoguesPegylated interferon-α

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Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Current chronic hepatitis B virus (HBV) treatments suppress replication but rarely achieve hepatitis B surface antigen (HBsAg) loss.
  • Functional HBV cure requires undetectable HBsAg and HBV DNA after finite therapy, alongside restored immune response.

Purpose of the Study:

  • To review the progress and challenges in developing finite therapies for functional HBV cure.
  • To evaluate the potential of novel direct-acting antivirals and immunomodulatory therapies, alone and in combination.

Main Methods:

  • Analysis of clinical trial data for direct-acting antivirals (DAAs) and immune modulatory therapies.
  • Focus on combination therapies, particularly those involving pegylated interferon-alfa (pegIFN-α).

Main Results:

  • DAAs and immunomodulatory therapies alone have not achieved HBV cure.
  • Recent combination trials, especially those including pegIFN-α, demonstrate promising results toward functional cure.
  • Further confirmation in larger studies with longer follow-up is needed.

Conclusions:

  • Combination therapy is a promising strategy for achieving functional HBV cure.
  • Development of simpler, safer, and orally administered regimens is crucial.
  • Safety remains paramount, and new therapies must offer clear advantages over long-term nucleos(t)ide analogue (NA) therapy.