Serological and molecular response on combined antiviral treatment in children with chronic hepatitis B after pediatric malignancy.

摘要

BACKGROUND: Chronic hepatitis B is a serious long-term problem for children surviving malignancy. The annual rate of spontaneous clearance of hepatitis B e antigen (HBeAg) is only 3% in these patients, and the response to monotherapy with interferon (IFN)-alpha is also low. OBJECTIVE: To monitor the serological and molecular response on combined antiviral treatment in children with chronic hepatitis B after pediatric malignancy. STUDY DESIGN: Twelve patients with a history of childhood malignancy and chronic hepatitis B were treated with prednisone for 4 weeks (0.6 mg/kg body weight per day orally for 3 weeks followed by 0.3 mg/kg body weight per day for 1 week) followed by IFN-alpha-2a (5 megaunits/m(2) body surface area, three times a week, subcutaneously) at least for 1 year. After 1 year of IFN-alpha monotherapy, treatment was discontinued in patients with HBeAg seroconversion as well as patients without HBeAg seroconversion and a decrease of serum hepatitis B virus (HBV) DNA level less than 0.5 logs of the basal level. Patients who had a decrease of the serum HBV DNA of more than 0.5 logs of the basal level underwent treatment continuation with IFN-alpha combined with famciclovir (FAM) (20 mg/kg body weight per day orally) for another year. RESULTS: After 1 year of IFN-alpha monotherapy, a decrease of the serum HBV DNA level to less than 0.5 logs was found in eight of 12 patients. Two of them additionally developed HBeAg seroconversion after 3 and 12 months. The remaining six patients received antiviral treatment with IFN-alpha combined with FAM for another year. Two of them showed HBeAg seroconversion after 21 and 24 months from study entry. HBeAg seroconversion was only observed in patients who had a decrease of serum HBV DNA to levels below 1 x 10(6) copies/ml. Treatment-induced toxicity was moderate and reversible in all patients. CONCLUSION: Combination treatment of chronic hepatitis B with prednisone, IFN-alpha, and FAM seems to be a safe and effective treatment option for children surviving pediatric malignancy.