The kinetics of
hepatitis B surface antigen (
HBsAg) levels preceding spontaneous
HBsAg seroclearance has not been fully investigated. The kinetics of
HBsAg and hepatitis B virus (HBV)
DNA of 203 treatment-naïve,
hepatitis B e antigen (
HBeAg)-negative patients with spontaneous
HBsAg seroclearance were compared with 203 age- and 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 area under the receiving operator characteristic (AUROC) of 0.833 (95% confidence interval [CI]: 0.792-0.873) and 0.803 (95% CI: 0.755-0.849), respectively. The optimal cut-off
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 levels ≥ 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).
CONCLUSION: