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Serum hepatitis B virus RNA decline alone does not predict treatment success. Concomitant decline in hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) is crucial for sustained response and HBsAg loss in chronic hepatitis B patients.

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Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Serum hepatitis B virus (HBV) RNA levels may indicate intrahepatic viral replication.
  • Novel antiviral therapies can significantly reduce HBV RNA without a corresponding decrease in hepatitis B surface antigen (HBsAg).
  • The clinical significance of this dissociation for off-treatment outcomes remains unclear.

Purpose of the Study:

  • To investigate the relationship between on-treatment decline of viral antigens (HBV RNA, HBsAg, HBcrAg) and off-treatment sustained response.
  • To assess the impact of concomitant HBsAg decline on sustained virologic response and HBsAg loss in patients with significant HBV RNA reduction.
  • To evaluate the predictive value of HBV RNA kinetics in relation to HBsAg and HBcrAg decline for treatment efficacy.

Main Methods:

  • Quantification of HBV RNA, HBsAg, and HBcrAg in patients with chronic hepatitis B undergoing peginterferon-based therapy.
  • Assessment of sustained response (HBV DNA <2000 IU/mL) and/or HBsAg loss post-treatment.
  • Stratification of patients based on on-treatment HBV RNA response and degree of HBsAg decline (<0.5, 0.5-1, >1 log).

Main Results:

  • A significant proportion of patients achieving HBV RNA response did not show a substantial HBsAg decline (>0.5 log).
  • On-treatment HBV RNA response was associated with higher rates of sustained response (27.4% vs 13.0%).
  • Among HBV RNA responders, sustained response was significantly higher in those with >1 log HBsAg decline (47.6%) compared to <0.5 log decline (16.0%).

Conclusions:

  • On-treatment HBV RNA decline alone is insufficient to predict sustained response or HBsAg loss.
  • Absence of concurrent HBsAg and/or HBcrAg decline alongside HBV RNA reduction is linked to lower treatment efficacy.
  • Future studies should incorporate kinetics of multiple biomarkers, including HBsAg and HBcrAg, to better evaluate antiviral efficacy in chronic hepatitis B.