Predictors of relapse in chronic hepatitis B after discontinuation of anti-viral therapy

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http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2011.04738.x/abstract

Predictors of relapse in chronic hepatitis B after discontinuation of anti-viral

therapy

Y. Liang1, J. Jiang1, M. Su1, Z. Liu1, W. Guo1, X. Huang1, R. Xie1, S. Ge1, J.

Hu1, Z. Jiang1, M. Zhu1, V. W.-S. Wong2, H. L.-Y. Chan2

Article first published online: 14 JUN 2011

DOI: 10.1111/j.1365-2036.2011.04738.x

© 2011 Blackwell Publishing Ltd

Issue

Alimentary Pharmacology & Therapeutics

Volume 34, Issue 3, pages 344–352, August 2011

Aliment Pharmacol Ther 2011; 34: 344–352

Summary

Background  Optimal duration of anti-viral therapy in chronic hepatitis B

virus (HBV) infection remains unclear.

Aim  To investigate factors that could predict relapse after stopping

anti-viral agents.

Methods  Chronic hepatitis B patients who were treated with anti-viral agents

(lamivudine, adefovir, entecavir) and have stopped the treatment were recruited.

Anti-viral agents were stopped according to the recommendations of the Asian

Pacific Association for the Study of the Liver. Virological relapse was defined

as an increase in serum HBV DNA to >1000 copies/mL after discontinuation of

treatment.

Results  Eighty-four (69 treatment naïve and 15 lamivudine resistant)

patients were eligible for this study. Thirty-seven patients developed

virological relapse at 4.3 ± 2.9 (range 1–11) months after discontinuation of

therapy. The 1-year cumulative probability of virological relapse was 42% and

47% in HBeAg (hepatitis B e antigen)-positive (n = 41) and HBeAg (hepatitis B e

antigen)-negative (n = 43) patients, respectively. On multivariate analysis by

proportional hazard model, pre-existing lamivudine resistance, delayed

suppression of HBV DNA to undetectable level during anti-viral therapy and to a

higher HBsAg (hepatitis B surface antigen) level at the end of treatment were

associated with virological relapse. Twelve of the 15 (80%) lamivudine resistant

patients developed virological relapse. Among the 11 treatment naïve patients

who had HBsAg ≤2 log IU/mL at the end of treatment, 1 (9%) of them had

virological relapse.

Conclusions  Treatment cessation among lamivudine resistant patients is

associated with high risk of virological relapse. Serum HBsAg level at the end

of treatment and rate of HBV DNA suppression can provide supplementary

information to guide the timing of stopping anti-viral drugs.