Hepatitis B surface antigen level complements viral load in predicting viral reactivation in spontaneous HBeAg seroconverters

Background and Aims The level of hepatitis B surface antigen ( HBsAg ) has been shown to complement hepatitis B virus ( HBV )‐ DNA level in predicting disease progression in hepatitis B e antigen ( HBeAg )‐negative patients, especially those with low viral loads. Whether this finding could be seen in spontaneous HBeAg seroconverters remains unclear. Methods A retrospective cohort of 390 T aiwanese spontaneous HBeAg seroconverters with a mean follow‐up period of 7.4 years was enrolled. The relationships between HBV ‐ DNA / HBsAg levels and HBeAg ‐negative hepatitis/active viral replication ( HBV ‐ DNA level ≥ 2000  IU /mL) were investigated. Results In the overall cohort, serum HBV ‐ DNA level served as a better predictor for HBeAg ‐negative hepatitis compared with HBsAg level. However, in those with HBV ‐ DNA level < 2000  IU /mL, a higher HBsAg level was associated with a higher risk of HBeAg ‐negative hepatitis ( P  = 0.015). Multivariate analysis showed the hazard ratio of HBsAg level ≥ 1000  IU /mL versus < 1000  IU /mL was 4.1 (95% confidence interval: 1.3–13.6). When using the end‐point of active viral replication, HBsAg ≥ 1000  IU /mL remained as an independent risk factor, with a hazard ratio of 2.5 (95% confidence interval: 1.1–5.9). Conclusions In spontaneous HBeAg seroconverters with HBV ‐ DNA level < 2000  IU /mL, HBsAg level ≥ 1000  IU /mL is associated with increased risks of HBeAg ‐negative hepatitis and active viral replication. Combining HBV ‐ DNA < 2000  IU /mL and HBsAg level < 1000  IU /mL may be used to define minimal viral activity.