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<http://onlinelibrary.wiley.com/doi/10.1002/hep.27083/abstract>
Distinct Seromarkers Predict Different Milestones of Chronic Hepatitis B
Progression
Jessica Liu1,
Hwai-I Yang1,2,3,
Mei-Hsuan Lee4,
Richard Batrla-Utermann5,
Chin-Lan Jen1,
Sheng-Nan Lu6,
Li-Yu Wang7,
San-Lin You1,
Chuhsing Kate Hsiao8,
Chien-Jen Chen1,8,*,
for the R.E.V.E.A.L.-HBV Study Group
DOI: 10.1002/hep.27083
Copyright © 2014 American Association for the Study of Liver Diseases
Vol. 59 Issue 3
Hepatology
Accepted Article (Accepted, unedited articles published online and citable.
The final edited and typeset version of record will appear in future.)
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.
(Hepatology 2014;)
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