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Background Telbivudine,one of the five nucleos(t)ide antiviral drugs,was reported to be superior to lamivudine in a better biochemical,virological,and histological response for treatment-naive patients in the GLOBE trial.The aim of this study was to determine the antiviral potency,viral resistance,and the significance of early response for long-term telbivudine treatment.Methods We recruited 161 patients of chronic hepatitis B (CHB) on telbivudine between January 2009 and September 2011 in Macau,China.The serum hepatitis B virus DNA levels,hepatitis B e antigen (HBeAg) seroconversion,alanine aminotransferese (ALT) normalization,and viral resistance were analyzed.Results The median age and follow-up duration were 48 years and 16.9 months.All patients were followed up for at least 6 months,while data were collected for 132,120,95,and 53 patients at 12,24,48,and 96 weeks respectively.The cumulative HBeAg seroconversion rate was 20.8％ and only three patients (1.9％) presented with telbivudine low level resistance.The ALT normalization rates were 76.9％ at 48 weeks and 77.6％ at 96 weeks.Undetectable HBV DNA was achieved by 1.8％,31.6％,60％,and 74.1％ in HBeAg positive patients and 29.3％,60.3％,84％,and 84.6％ in HBeAg negative patients at each time point.Week 12 HBV DNA level ＜1000 copies/ml (＜200 IU/ml) was a better predictor of viral suppression at 2-year follow-up (P=-0.001,OR=27.00) than undetectable HBV DNA level at week 24 (P=0.120,OR=4.81).Conclusions Two-year telbivudine treatment yielded high rates of viral suppression and ALT normalization.Serum HBV DNA level at week 12 is a superior predictor for long-term viral suppression.