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Hepatitis B functional cure: Current and future perspective.

Sudheer Marrapu1, Jinit R Soni1, Kislaya Kamal1

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Achieving a functional cure for chronic hepatitis B (CHB) requires hepatitis B surface antigen (HBsAg) loss. Current treatments show limited success, necessitating novel therapies to overcome CHB pathogenesis barriers.

Keywords:
Functional cureHepatitis BHepatitis B surface antigen seroclearanceSurface antigenVirological cure

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Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Chronic hepatitis B (CHB) affects over 250 million globally.
  • A functional cure, marked by HBsAg loss and undetectable HBV DNA, is the primary treatment goal.
  • CHB pathogenesis, including viral DNA integration and immune dysfunction, hinders HBsAg clearance.

Purpose of the Study:

  • To review the current understanding of HBsAg seroclearance in CHB.
  • To discuss the clinical significance and challenges in achieving a functional cure for CHB.
  • To explore the evolving treatment landscape for CHB.

Main Methods:

  • Review of current literature on CHB pathogenesis and treatment.
  • Analysis of existing therapeutic outcomes for HBsAg seroclearance.
  • Discussion of novel therapeutic strategies and their potential.

Main Results:

  • Current therapies (NAs, pegylated interferon) yield low HBsAg seroclearance rates (3-14%).
  • Significant barriers to HBsAg clearance include viral persistence and impaired immunity.
  • Novel antivirals and immunotherapies are under investigation.

Conclusions:

  • Achieving a functional cure for CHB remains challenging due to complex viral and host factors.
  • New therapeutic approaches targeting the HBV life cycle and immune responses are crucial.
  • Careful patient selection for NA cessation may aid HBsAg loss but requires vigilant monitoring.