AIM: To determine the virological and biochemical relapse rates in Chinese CHB patients with lamivudine-induced HBeAg seroconversion after stopping lamivudine therapy, and to identify significant viral or biochemical factors predictive of subsequent relapse. METHODS: All patients from all Hepatology Clinic with lamivudine-induced HBeAg seroconversion with subsequent cessation of lamivudine therapy were recruited. Liver biochemistry, HBeAg, anti-HBe, and serum HBV DNA by PCR (COBAS Taqman) was determined at the time of stopping lamivudine, at 3 months, 6 months, 1 year, and yearly thereafter. RESULTS: Twenty-two patients were included, of which 16(73%) were male with a median age of 32 years (range, 21-55). The median duration of follow-up was 104 months (range, 31-150). Six (27%) patients had undetectable HBV DNA by PCR at the time of stopping lamivudine treatment. In total, 7(32%) patients had subsequent flare (as defined by ALT >2x upper limit of normal), with associated virological rebound of HBV DNA (as defined by 1 log increase from time of stopping therapy). The cumulative incidence of flare at 5 years was 44%, all occurring before 25 months. There was no significant difference in the cumulative incidence of flares between those patients that continued lamivudine for 6-12 months, 1-2 years and over 2 years after HBeAg seroconversion (p=0.58). In patients who had normal ALT and undetectable HBV DNA, their cumulative incidence of flare was not significantly different to those that had detectable HBV DNA or abnormal ALT at time of stopping lamivudine (p=0.73). Two patients underwent HBeAg seroreversion at 5 and 10 months, with resulting flares. The cumulative incidence of HBeAg seroreversion after stopping lamivudine was 9% at 5 years. Fourteen (64%) patients underwent virological rebound, with a cumulative incidence of 82% at 4 years. There was no significant difference in the cumulative incidence of virological rebound in patients with undetectable HBV DNA at the time of stopping lamivudine therapy compared to those with detectable HBV DNA. Of those with virological rebound, 8(57%) had HBV DNA >105 copies/ml. Neither patient age or gender, genotype, presence of precore or core promoter mutations were significant factors in subsequent flare or virological rebound after stopping lamivudine therapy. CONCLUSION: Despite the high sustained HBeAg seroconversion (81%) after stopping lamivudine, HBV DNA rebound occurred in 64%, of which 57% had HBV DNA >105 copies/ml and 32% had ALT flares. Patients who had both normal ALT and undetectable HBV DNA by PCR at the time of stopping lamivudine therapy did not have a lower cumulative incidence of flares.

link_to_OA_fulltext