Large-scale profile study on hepatitis B surface antigen levels in chronic hepatitis B: implications for drug...

Area of Science:

• Hepatology and Virology
• Biomarker Discovery
• Drug Development

Background:

• Quantitative hepatitis B surface antigen (qHBsAg) is a critical biomarker for managing chronic hepatitis B (CHB).
• Understanding qHBsAg profiles is essential for assessing disease progression and treatment efficacy.

Purpose of the Study:

• To establish quantitative hepatitis B surface antigen (qHBsAg) profiles in a large chronic hepatitis B (CHB) cohort.
• To guide the development of novel antiviral therapies for CHB.

Main Methods:

• Analysis of baseline qHBsAg levels, longitudinal qHBsAg trajectories, and predictors of HBsAg seroclearance in 4287 CHB patients (2009-2020).
• Assessment of treatment-naïve and nucleos(t)ide analogue (NUC)-treated patients.
• Identification of independent determinants for low qHBsAg levels and predictors for HBsAg seroclearance.

Main Results:

• Median baseline qHBsAg was 630.8 IU/mL; 45.2% of patients were on NUCs.
• Significant proportions of patients had baseline qHBsAg <3000, <1000, or <100 IU/mL, with variations between treatment-naïve and NUC-treated groups.
• Age, HBeAg positivity, and HBV DNA levels were independent determinants of qHBsAg levels. Median qHBsAg reduction was 0.10 log IU/mL/year.
• HBsAg seroclearance was achieved by 12.3% of patients over a median follow-up of 6.3 years.
• A baseline alanine aminotransferase/qHBsAg ratio ≥0.27 independently predicted HBsAg seroclearance (HR 4.904, p<0.001).

Conclusions:

• In endemic populations, over 40% of CHB patients exhibit qHBsAg >1000 IU/mL.
• These patients demonstrate limited spontaneous HBsAg seroclearance and suboptimal responses to novel antivirals.
• The established qHBsAg profiles and identified predictors have significant implications for the design and development of new CHB therapies.