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Article first published online: 10 JUL 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 3, pages 812–819, September 2012
How to Cite
Seto, W.-K., Wong, D. K.-H., Fung, J., Hung, I. F.-N., Fong, D. Y.-T., Yuen, J. C.-H., Tong, T., Lai, C.-L. and Yuen, M.-F. (2012), A large case-control study on the predictability of hepatitis B surface antigen levels three years before hepatitis B surface antigen seroclearance. Hepatology, 56: 812–819. doi: 10.1002/hep.25718
Potential conflict of interest: Nothing to report.
The assays used to determine serum hepatitis B virus DNA levels (Cobas Taqman assay) and hepatitis B surface antigen levels (Elecsys HBsAg II assay) performed in our laboratory were supported by an unrestricted grant from Roche Diagnostics.
- Issue published online: 28 AUG 2012
- Article first published online: 10 JUL 2012
- Accepted manuscript online: 15 MAR 2012 12:00AM EST
- Manuscript Accepted: 1 MAR 2012
- Manuscript Received: 11 OCT 2011
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: 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. (HEPATOLOGY 2012;56:812–819)