Hepatitis B core-related antigen kinetics predict spontaneous HBeAg seroclearance in chronic hepatitis B patients.

Background and aims: Hepatitis B e antigen (HBeAg) seroclearance is crucial in the natural history of chronic hepatitis B (CHB). Little is known about the role of hepatitis B core-related antigen (HBcrAg) levels in predicting spontaneous HBeAg seroclearance.

Methods: This retrospective cohort study included 484 treatment-naïve HBeAg-positive CHB patients with an extended follow-up period at National Taiwan University Hospital. The primary endpoint was spontaneous seroclearance of HBeAg. The association between baseline HBcrAg levels and their kinetic patterns with spontaneous HBeAg seroclearance was assessed.

Results: Of 484 patients with a mean follow-up period of 7.80 years, 331 (68.4%) achieved spontaneous HBeAg seroclearance, corresponding to an annual rate of 8.76%. Lower baseline HBcrAg levels correlated with an increased likelihood of HBeAg seroclearance (log-rank P < .001). When HBcrAg kinetics were assessed based on baseline and year 3 levels, patients with HBcrAg levels persistently < 10⁵ KU/mL (HR: 2.66; 95% CI: 1.75-4.04) and those declining to < 10⁵ KU/mL (HR: 2.31; 95% CI: 1.50-3.55) had an increased likelihood of HBeAg seroclearance when compared to those with persistently high HBcrAg levels. This association remained statistically significant in multivariate analysis after adjusting for baseline viral factors. In addition, HBcrAg kinetics were consistently associated with HBeAg seroclearance in immune-tolerant patients.

Conclusions: HBcrAg < 10⁵ KU/mL, or a decline to this threshold, identified HBeAg-positive CHB patients with higher likelihood of spontaneous HBeAg seroclearance. Persistently high HBcrAg may indicate earlier CHB phases and inform management strategies.