['Effective management of chronic hepatitis B infection is still very challenging, despite decades of clinical research. Telbivudine is one of the most frequently used antiviral drug at the current stage, but its long-term effectiveness, particularly at off-treatment, is still unclear.', 'To assess on-treatment HBsAg kinetics in patients treated with telbivudine for 2 years, and predicting sustained virologic response (SR) at 2 years off-treatment.', 'Serum HBV DNA/HBsAg levels were assessed from 17 HBeAg+ patients treated with telbivudine 600 mg/day for 104 weeks, at baseline, weeks 24, 52 and 104, as well as during off-treatment follow-up.', 'HBsAg levels <2 log(10)IU/ml at treatment week 104 were highly predictive of SR (i.e., HBV DNA <300 copies/ml, HBeAg seroconversion, ALT normalization) at 2 years off-treatment (positive predictive value [PPV], 93%; negative predictive value [NPV], 100%). HBsAg levels consistently declined from baseline only in patients achieving SR during 2 years off-treatment. At weeks 24 and 52, HBsAg decline rate was a better predictor of off-treatment response than HBV DNA decline rate. HBsAg decline rates of >0.8 and >1 log(10)IU/ml at treatment weeks 24 and 52 were predictive of SR (PPV, 75%; NPV, 86% at week 24; PPV, 75%; NPV, 86% at week 52).'] Is on-treatment serum HBsAg level predictive of sustained off-treatment virologic response to telbivudine in HBeAg-positive chronic hepatitis B patients?