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Abstract Details
Distinct Seromarkers Predict Different Milestones of Chronic Hepatitis B Progression
Liu J1, Yang HI, Lee MH, Batrla-Utermann R, Jen CL, Lu SN, Wang LY, You SL, Hsiao CK, Chen CJ; for the R.E.V.E.A.L.-HBV Study Group. Hepatology. 2014 Feb 20. doi: 10.1002/hep.27083. [Epub ahead of print]
Author information
1The Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Abstract
Background and Aims: Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and HBV DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigates the role of serum hepatitis B surface antigen (HBsAg) levels and establishes prediction models for predicting HBeAg seroclearance and HBV DNA undetectability. Methods: A total of 2139 HBsAg-seropositive, anti-HCV-seronegative, and treatment-naïve participants without liver cirrhosis at study entry were included. Spontaneous HBeAg seroclearance and HBV DNA undetectability were analyzed in 431 HBeAg-seropositive participants, and 1708 HBeAg-seronegative participants, respectively. Regression coefficients of predictors in Cox proportional hazard models were converted into integer scores for predicting seroclearance, and predictive accuracy was assessed with time-dependent ROC curves. Results: HBV DNA level was the most important predictor of HBeAg seroclearance, but Serum HBsAg level was the most significant predictor of HBV DNA undetectability. Compared to individuals with HBsAg levels ≥10,000 IU/mL, the multivariate-adjusted rate ratio (95% confidence interval) of HBV DNA undetectability was 1.20 (0.62-2.30), 2.49 (1.31-4.75), and 6.08 (3.19-11.61) for those with serum HBsAg levels of 1000-9999, 100-999, and <100 IU/mL, respectively. The AUROCs of the prediction models for predicting the five- and ten-year probabilities of HBeAg seroclearance and HBV DNA undetectability were 0.85 (0.80-0.90) and 0.78 (0.73-0.83) for HBeAg seroclearance, and 0.77 (0.72-0.82) and 0.73 (0.70-0.76) for HBV DNA undetectability. Conclusion: Prediction models incorporating important host and virus factors can predict HBeAg seroclearance and HBV DNA undetectability. Serum HBsAg levels rather than HBV DNA is the most important predictor of spontaneous HBV DNA undetectability. Serum HBsAg levels should be monitored in the management of patients with HBeAg-seronegative chronic hepatitis B.