Combined lamivudine/interferon-alpha treatment in "immunotolerant" children perinatally infected with hepatitis B: a pilot study

OBJECTIVE: To investigate whether combining the antiviral effect of lamivudine with the immune-boosting action of interferon-alpha (IFN-alpha) is effective in treating hepatitis B virus (HBV) "immunotolerant" children. STUDY DESIGN: Twenty-three children (8 boys; mean age, 10 years) infected during the first year of life (17 Asian, 21 with normal aminotransferase levels, 15 with HBV-DNA >1000 pg/mL by hybridization and all with mild histologic changes) were treated with lamivudine (3 mg/kg) for 8 weeks alone and then lamivudine (3 mg/kg) and IFN-alpha (5 MU/m(2), 3 times weekly) in combination for 10 months. RESULTS: Seventy-eight percent became HBV-DNA negative at the end of treatment, 5 (22%) seroconverted to anti-HBe, 4 (17%) of whom achieved complete viral control, becoming persistently HBsAg negative and anti-HBs positive. None had YMDD mutations. The viral status of the patients has not changed after a median follow-up of 40 months (range, 36 to 48). CONCLUSIONS: This pilot study suggests that lamivudine pretreatment followed by a combination of lamivudine and IFN-alpha can induce complete viral control in HBV immunotolerant children, hitherto considered poor responders.