BACKGROUNDS/AIMS: Continuation of lamivudine therapy is controversial for patients with chronic hepatitis B when viral breakthrough occurs. Moreover, the effect of continuous lamivudine therapy is unknown in patients with acute exacerbation after viral breakthrough. We assessed clinical course of acute exacerbation after viral breakthrough in patients who continued and discontinued lamivudine therapy. METHODS: Medical records of 109 patients with viral breakthrough during lamivudine therapy were reviewed. Of 40 patients with acute exacerbation (ALT level > 5 x ULN), adefovir dipivoxil was unavailable in 38 patients. These 38 patients (mean age 42.6 years; male/female, 34/6) were divided into continuation (n=21) and discontinuation (n=17) groups. Clinical courses of the 2 groups were compared. RESULTS: During follow-up period (mean, 27 months; range, 6-60 months), ALT levels decreased to < 2 x ULN in 11 patients (52%) of continuation group and 9 patients (53%) of discontinuation group, varied from 2 x to 5 x ULN in 9 (43%) and 5 (29%), respectively, and increased to > 5 x ULN in 1 (5%) and 3 (18%), respectively, with no statistical significance (P=.417). CONCLUSIONS: When acute exacerbation of ALT levels occurs after viral breakthrough during lamivudine administration in patients with compensated chronic hepatitis B, continuation of lamivudine may have no advantage over discontinuation.