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Dynamics of HBV biomarkers during nucleos(t)ide analog treatment: A 14-year study

Florian van Bömmel1, Elisabetta Degasperi2, Alena van Bömmel3

  • 1Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany.

Hepatology Communications
|May 16, 2025
PubMed

Insights

Long-term nucleos(t)ide analog (NA) treatment for chronic hepatitis B (CHB) increases the likelihood of achieving functional cure biomarkers. These biomarkers, including HBsAg, HBV RNA, and HBcrAg, are crucial for monitoring treatment response and guiding NA discontinuation in CHB patients.

Area of Science:

  • Hepatology
  • Virology
  • Biomarker Research

Background:

  • Chronic hepatitis B (CHB) management involves nucleos(t)ide analog (NA) therapy.
  • Hepatitis B surface antigen (HBsAg), HBV RNA, and hepatitis B core-related antigen (HBcrAg) are key biomarkers.
  • Assessing these biomarkers aids in predicting treatment response and potential NA discontinuation.

Purpose of the Study:

  • To investigate the long-term kinetics of HBsAg, HBV RNA, and HBcrAg.
  • To evaluate these biomarkers as predictors of functional cure after NA discontinuation in CHB patients.
  • To analyze biomarker trends during extended NA treatment (up to 14 years).

Main Methods:

  • Retrospective analysis of a prospective cohort study.
  • Inclusion of 96 HBeAg-negative CHB patients (HBV genotype D) on tenofovir disoproxil fumarate.
  • Measurement of HBsAg, HBV RNA, and HBcrAg in 384 serum samples; definition of functional cure endpoints.

Main Results:

  • HBV RNA and HBcrAg were initially detectable in most patients.
  • Detectable HBV RNA decreased significantly over 8-14 years of NA treatment.
  • Combined biomarker endpoints for functional cure increased progressively during long-term NA therapy.

Conclusions:

  • Long-term NA treatment is associated with improved HBV biomarker profiles.
  • Achieving specific HBsAg, HBV RNA, and HBcrAg levels indicates a higher likelihood of functional cure.
  • These biomarkers are valuable for monitoring CHB patients undergoing extended NA therapy.
Abstract

Keywords:
HBV biomarkersHBcrAgfunctional curestop NUCtreatment discontinuation

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