Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy

In patients with chronic hepatitis B, brief lamivudine therapy suppresses h epatitis B virus (HBV) DNA but results infrequently in sustained losses of virus replication posttreatment. We evaluated treatment response and its po sttreatment durability during up to 18 months of lamivudine therapy (100 mg /d) in 24 patients who had hepatitis B e antigen (HBeAg) despite 1 to 3 mon ths of prior therapy. Therapy was to be stopped after HBeAg loss or serocon version (acquisition of antibody to HBeAg); posttreatment monitoring contin ued for 6 months. During therapy, which was well tolerated, HBV DNA became undetectable in all evaluable patients, accompanied by reduced alanine tran saminase (ALT) activity. The cumulative 18-month confirmed loss of HBeAg du ring therapy was 9 of 24 (38%) and seroconversion was 5 of 24 (21%), Therap y was discontinued after HBeAg loss/seroconversion in 7 patients, and HBeAg status was maintained in all. Four of the patients with HBeAg responses lo st HBsAg at least once. In 10 (43%) of 23 patients tested, we identified HB V polymerase YMDD mutations, 3 with detectable HBV DNA (2 with ALT elevatio ns) and 7 without virological/biochemical breakthrough, In conclusion, up t o 18 months of lamivudine therapy was well tolerated, suppressed HBV replic ation consistently and tripled the frequency of HBeAg losses observed durin g brief-duration therapy; HBeAg loss/seroconversion remained durable posttr eatment, The emergence of YMDD-variant HBV was relatively common but occurr ed typically without reappearance of detectable HBV DNA or ALT elevation. O ur observations suggest that lamivudine can be stopped after confirmed HBeA g loss or seroconversion.