The Duration of Lamivudine Therapy for Chronic Hepatitis B: Cessation vs. Continuation of Treatment After HBeAg Seroconversion

OBJECTIVES: The aim of this study was to compare the virological and biochemical relapse rates in Asian chronic hepatitis B patients with lamivudine-induced hepatitis B e antigen (HBeAg) seroconversion, between those who stopped therapy after HBeAg seroconversion and those who continued to receive lamivudine. METHODS: All patients with lamivudine-induced HBeAg seroconversion were included. Patients who stopped lamivudine after HBeAg seroconversion (n=22) were compared with 79 patients who continued to receive lamivudine (n=79). Demographic, virological, and biochemical parameters were recorded at baseline, and throughout the duration of follow-up. RESULTS: In patients who stopped lamivudine, the median follow-up after stopping lamivudine was 20 months. Of these patients, 14 (64%) had virological rebound, with a cumulative incidence of 82% at 4 years. There was no significant difference in number of flares between patients with normal alanine aminotransferase (ALT) and undetectable hepatitis B virus (HBV) DNA at the time of stopping lamivudine compared with that in patients with either abnormal ALT, detectable HBV DNA, or both (P=0.73). The cumulative incidence of HBeAg seroreversion and ALT flares at 5 years after stopping lamivudine was 9 and 44%, respectively. Of the 79 patients who continued with lamivudine, 62 (78%) had undetectable HBV DNA at the time of last follow-up, whereas no patients had undetectable HBV DNA after stopping lamivudine (P<0.001). The cumulative incidence of ALT flares at 5 years was 16% (P<0.001 compared with those who stopped taking lamivudine). After a median treatment duration of 79 months, lamivudine-resistant mutations occurred in eight patients (10%). CONCLUSIONS: In Asian HBeAg-positive patients, continuing with lamivudine after achieving HBeAg seroconversion was associated with a higher proportion of undetectable HBV DNA and a lower number of ALT flares, when compared with those with cessation of lamivudine. In patients who achieved HBeAg seroconversion with lamivudine, the resistance rate was not high when treatment was continued after HBeAg seroconversion.