Prediction of the response to peg-interferon-alfa in patients with HBeAG positive chronic hepatitis B using decline of HBV DNA during treatment
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 log10 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 log10.
|Keywords||Antiviral therapy, Dynamic prediction, HBV DNA decline, Hepatitis B virus, PEG-IFN, Response|
|Persistent URL||dx.doi.org/10.1002/jmv.21778, hdl.handle.net/1765/20663|
Hansen, B.E., Buster, E.H.C.J., Steyerberg, E.W., Lesaffre, E.M.E.H., & Janssen, H.L.A.. (2010). Prediction of the response to peg-interferon-alfa in patients with HBeAG positive chronic hepatitis B using decline of HBV DNA during treatment. Journal of Medical Virology, 82(7), 1135–1142. doi:10.1002/jmv.21778