Lamivudine treatment for chronic hepatitis B infection in children unresponsive to interferon

Abstract

Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. This prospective open study reports the results of lamivudine treatment in children with chronic hepatitis B infection who did not respond to previous interferon treatment. Lamivudine, 3 mg/kg/day (maximum, 100 mg/day), was given for 52 weeks to 20 children and adolescents, ages 8.5 to 19 years, with chronic hepatitis B infection who had been treated with interferon 2 to 5 years earlier. We evaluated virologic and biochemical responses, the occurrence of YMDD mutants and adverse effects. All children were HBV DNA+, hepatitis B e antigen (HBeAg) /anti-hepatitis B e antibody- at start of treatment. At the end of 1 year, HBV DNA declined by 95% in all patients, and 8 of 18 (44%) had sustained undetectable HBV DNA by hybridization assay. Median pretreatment alanine aminotransferase (ALT) x1.5 upper limit of normal decreased to ALT x0.9 upper limit of normal after 1 year. One child became HBeAg-negative. YMDD mutants were detected in 11 of 17 (65%) children after 1 year of lamivudine treatment. Among children with YMDD mutant variants, 54% maintained normal ALT values and 45% had undetectable HBV DNA by hybridization assay. No adverse effects were observed. Children with chronic hepatitis B infection treated with lamivudine after failure of interferon therapy had decreased HBV replication and improved ALT values. However, lamivudine treatment resulted in an exceptionally high rate of lamivudine-resistant mutants and low HBeAg seroconversion rate.