Comparison of two different regimens of combined interferon-alpha 2a and lamivudine therapy in children with chronic hepatitis B infection

Abstract

Aim: To evaluate the efficacy of two regimens of combined interferon-alpha 2a (IFN-alpha 2a) and lamivudine (3TC) therapy in childhood chronic hepatitis B. Methods: A total of 177 patients received IFN-alpha 2a, 9 million units (MU)/m(2) for 6 months. In group 1 (112 patients, 8.7 +/- 3.5 years), 3TC (4 mg/kg/day, max 100 mg) was started simultaneously with IFN-alpha 2a, in group 11 (65 patients, 9.6 +/- 3.8 years) 3TC was started 2 months prior to IFN-alpha 2a. 3TC was continued for 6 months after antiHBe seroconversion or stopped at 24 months in non-responders. Results: Baseline alanine aminotransferase (ALT) was 134.2 +/- 34.1 and 147.0 +/- 45.3; histological activity index (HAI) was 7.4 +/- 2.7 and 7.1 +/- 2.3; and HBV DNA levels were above 2,000 pg/ml in 76% and 66% of patients in groups I and 11, respectively (P > 0.005). Complete response was 55.3% and 27.6% in groups I and 11, respectively (P < 0.01). AntiHBe seroconversion was higher and earlier, and HBV DNA clearance was earlier in group I (P < 0.05). HBsAg clearance was 12.5% and 4.6% and antiHBs seroconversion was 9.8% and 6.2% in groups I and 11, respectively (P > 0.05). Breakthrough occurred in 17.9% and 24.6%; breakthrough times were 15.9 +/- 4.6 and 14.1 +/- 5.1 months; and relapse rates were 6.8% and none in groups I and 11, respectively (P > 0.05, P > 0.05, P > 0.05). Responders had higher HAI (HAI > 6) and higher pre-treatment ALT than non-responders. Conclusion: Simultaneous 3TC+IFN-alpha 2a yields a higher response and earlier antiHBe seroconversion and viral clearance than consecutive combined therapy. Relapse rate is low. Predictors of response are high basal ALT and high HAI scores. 3TC can be administered for 24 months without any side effect and breakthrough rate is comparable with previous studies.