Pretreatment alanine transaminase (ALT) elevation may be used as a predictor for higher hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B patients. However, the role of dynamic changes of on-treatment ALT for seroconversion is unknown. A total of 170 naïve HBeAg-positive chronic hepatitis B patients were treated with a nucleosidenucleotide analogues (NA), either lamivudine, adefovir, entecavir, or telbivudine, for at least 2 years and followed up for 1 more year. Clinical characteristics were detected and analysed at baseline and at 3-month intervals. On-treatment ALT predicted HBeAg seroconversion more accurately than baseline ALT. Among the patients with on-treatment ALT ≤1 × UNL, 1-≤2 × UNL, 2-≤5 × UNL and >5 × UNL, HBeAg seroconversion was 11.4, 5.4, 24.4 and 65.0% (odds ratio = 1.0, 0.4, 2.5 and 14.4, respectively), respectively. Moreover, two modelstypes of seroconversion were observed. Type I was characterized by rapidly decreased ALT and HBV DNA during the first 3-month interval, but with high HBeAg reversion rate (50%) after consolidation treatment. Type II was a slow decreased DNA procedure accompanied by significant elevated ALT with less reversion (23%). Receiver operating characteristic curve analysis showed a 1.9-fold increased ALT ratio (present visit ALT: previous visit ALT) accompanied by at least a 0.8 log decreased HBV DNA may be used to classify these two seroconversion types. We conclude that on-treatment elevated ALT levels is a better predictor for seroconversion after NAs treatment, and HBV DNA profiles may help to identify different models of seroconversion. © 2009 Blackwell Publishing Ltd.