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Distinct seromarkers predict different milestones of chronic hepatitis B progression
Author(s) -
Liu Jessica,
Yang HwaiI,
Lee MeiHsuan,
BatrlaUtermann Richard,
Jen ChinLan,
Lu ShengNan,
Wang LiYu,
You SanLin,
Hsiao Chuhsing Kate,
Chen ChienJen
Publication year - 2014
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.27083
Subject(s) - chronic hepatitis , medicine , hepatology , virology , virus
Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigated the role of serum hepatitis B surface antigen (HBsAg) levels and established models for predicting HBeAg seroclearance and HBV DNA undetectability. A total of 2,139 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 1,708 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 receiver operating characteristic (ROC) curves. The 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 1,000‐9,999, 100‐999, and <100 IU/mL, respectively. The area under the ROC curve (AUROC) of the prediction models for predicting the 5‐ and 10‐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. (H epatology 2014;60:77–86)