Combining the HBsAg decline and HBV DNA levels predicts clinical outcomes in patients with spontaneous HBeAg seroconversion

Purpose: The aim was to investigate whether the quantitation of the hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels can predict HBV reactivation and advanced liver disease after spontaneous hepatitis B e antigen (HBeAg) seroconversion. Methods: A total of 121 patients who experienced spontaneous HBeAg seroconversion were included in this longitudinal study. Serial HBsAg and HBV DNA levels were measured before and after HBeAg seroconversion. Results: Of the 121 patients, 32 experienced HBV reactivation and six achieved an HBsAg loss after HBeAg seroconversion during the follow-up period. The decline in the HBsAg level was considerably more pronounced in patients without HBV reactivation when compared to those with HBV reactivation (p = 0.016). Multivariate analysis revealed that the age of >40 years at HBeAg seroconversion, male sex, and HBsAg decline, and HBV DNA levels at month 12 after HBeAg seroconversion were independent factors for the development of HBeAg-negative hepatitis. All the six patients who achieved HBsAg loss had HBsAg level of <1,000 IU/mL at month 12 after HBeAg seroconversion (p < 0.001). The risk of HBeAg-negative hepatitis, cirrhosis, and HCC was substantially increased in patients who had a combination of both, i.e., no decline in the HBsAg level and HBV DNA level of >10⁴ copies/mL at month 12 after HBeAg seroconversion. Conclusions: Combining HBsAg reduction and HBV DNA levels at month 12 after HBeAg seroconversion was a useful marker to predict clinical outcomes in spontaneous HBeAg seroconverters. HBsAg level of <1,000 IU/mL at month 12 after HBeAg seroconversion could predict the HBsAg loss after HBeAg seroconversion.