567 CHIR99021 (range, −0.984-2.233) and 0.106 log IU/mL/year (range, −0.375-1.189), respectively (P < 0.001). The optimal HBsAg annual log reduction to predict HBsAg seroclearance was 0.5 log (Youden's index, 5.15; sensitivity, 62.8%; specificity, 88.7%). One hundred and seven patients with HBsAg seroclearance (52.7%) achieved ≥0.5 log reduction from 3 to 2 years, significantly more than 17 (8.4%) patients in the control group (P < 0.001). We further examined patients with serum HBsAg ≥200 IU/mL at 3 years (n = 33 and 150 for patients with HBsAg

seroclearance and controls, respectively). In this subgroup of patients, the AUC for HBsAg log reduction was 0.867 (P < 0.001; 95% confidence interval [CI]: 0.778-0.956), with a 0.5-log reduction most optimal in predicting HBsAg seroclearance (Youden's index, 6.35; sensitivity, 74.1%; specificity, 89.4%). For

patients with serum HBsAg <200 IU/mL (n = 170 and 53, respectively), the AUC for HBsAg log reduction was comparably lower at 0.796 (P < 0.001; 95% CI: 0.724-0.868). We also examined whether the addition of HBV DNA into HBsAg levels could improve the AUC for predicting HBsAg seroclearance. We found that there was no increase in AUCs using different combinations of HBsAg and HBV DNA in terms of their absolute levels and reductions (data not shown). Analyzing HBsAg among patients with undetectable HBV DNA levels produced an AUC of only 0.648 (P = 0.013; 95% CI: 0.538-0.823). SCH727965 Among the subgroups of patients with HBsAg ≥200 IU/mL, HBV DNA log reduction also produced an AUC of only 0.735 上海皓元 (P < 0.001; 95% CI: 0.623-0.848). Our current study demonstrated the kinetics of serum HBsAg and HBV DNA levels preceding HBsAg seroclearance in a large population of CHB patients with HBsAg seroclearance. To our knowledge, this is a study with the largest number of patients with HBsAg seroclearance to date (n = 203). Our present study outlines the changes in HBsAg kinetics before spontaneous HBsAg seroclearance. The enrollment of age- and

sex-matched controls would allow us to optimally delineate the differences in serologic and virologic kinetics between the two patient groups. With 3 years of serial data, we were able to show a marked difference in HBsAg levels between patients with HBsAg seroclearance and controls. In our study, the median HBsAg levels of controls were between 366 and 846 IU/mL at different time points, levels which were similar to those reported in other studies on serum HBsAg levels in HBeAg-negative CHB.13-15 The results of our control group also provide additional insight into the natural history of HBsAg levels in HBeAg-negative CHB. Serum HBsAg levels decreased gradually over time and appears to be a much more stable marker than HBV DNA levels, which are known for their fluctuating nature.25 Our study confirms that serum HBsAg measurements can be an important tool for physicians in weighing the chances of HBsAg seroclearance in the long term.