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J Med Virol. 2010 Jul;82(7):1135-42. doi: 10.1002/jmv.21778.

Prediction of the response to peg-interferon-alfa in patients with HBeAg positive chronic hepatitis B using decline of HBV DNA during treatment.

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Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.


Peginterferon (PEG-IFN) results in HBeAg loss combined with virologic response in only a minority of patients with HBeAg positive chronic hepatitis B. Baseline predictors of response to PEG-IFN include HBV-genotype, pre-treatment HBV DNA levels, and ALT. The aims of this study were to develop a model, which improves the baseline prediction of response to PEG-IFN for individual patients by including early HBV DNA measurements during treatment and to establish an early indication for cessation of treatment. One hundred thirty-six patients treated with PEG-IFN were included in the study. Response was defined as loss of HBeAg and HBV DNA <10,000 copies/ml at 26 weeks post-treatment. Logistic regression analysis techniques were used to develop a dynamic prediction model with HBV DNA during the first 32 weeks of therapy. An early clinically useful rule for dis(continuation) of treatment was identified with a grid of cut-off values of HBV DNA decline during treatment. Adding HBV DNA decline to baseline prediction increased c-statistics from 0.846 to 0.857, 0.855 to 0.866 at weeks 4, 12, and 24. A HBV DNA decline of at least 2 log(10) within 24 weeks was strongly associated with response when added to the baseline prediction model: OR 5.7 (95% CI: 1.70-20.0; P = 0.004). A dynamic model including HBV DNA decline during treatment provides more accurate predictions of response to PEG-IFN. The model strongly supports individual decision making on treatment (dis)continuation in patients with HBeAg positive chronic hepatitis B. It is recommended that PEG-IFN treatment is stopped by 24 weeks if HBV DNA declined <2 log(10).

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