Source Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hong Kong.

The kinetics of hepatitis B surface antigen (HBsAg) levels prior to spontaneous HBsAg seroclearance has not been fully investigated. The kinetics of HBsAg and HBV DNA of 203 treatment-naïve, hepatitis B e antigen (HBeAg)-negative patients with spontaneous HBsAg seroclearance were compared with 203 age-, sex-matched HBeAg-negative controls. Serum samples at 3 years, 2 years, 1 year and 6 months before HBsAg seroclearance and at the time of HBsAg loss were tested. Median HBsAg levels at these respective time points before HBsAg seroclearance were 23.5, 3.51, 0.524 and 0.146 IU/mL. For all time points, patients with HBsAg seroclearance had significantly lower median HBsAg and HBV DNA levels compared to those of the controls (all p<0.001). Median HBsAg and HBV DNA levels declined significantly until HBsAg seroclearance (p<0.001). Although median HBsAg levels also decreased significantly with time (p=0.006) in controls, median HBV DNA levels remained similar (p=0.414). Serum HBsAg levels, followed by HBsAg log reduction, were the best predictors of HBsAg seroclearance, with an AUROC of 0.833, [95% confidence interval (CI) 0.792-0.873] and 0.803 (95% CI 0.755-0.849) respectively. The optimal cutoff HBsAg level and HBsAg reduction to predict HBsAg seroclearance were <200 IU/mL (sensitivity 84.2%, specificity 73.4%) and 0.5 log IU/mL/year (sensitivity 62.8% specificity 88.7%) respectively. For patients with HBsAg level ≥200 IU/mL, an annual 0.5 log reduction was highly predictive of subsequent HBsAg seroclearance (AUROC 0.867, 95% CI 0.778-0.956). To conclude, serum HBsAg <200 IU/mL and 0.5 log reduction in HBsAg were predictive of HBsAg seroclearance within 3 years of follow-up. These parameters may serve as good indicators for the consideration of treatment duration and cessation for chronic hepatitis B.