LONG TERM LAMIVUDINE TREATMENT FOR CHRONIC HEPATITIS B INFECTION IN CHILDREN UNRESPONSIVE TO INTERFERON

Abstract

Background: Three years ago we reported the results of an open prospective study that investigated the efficacy and safety of one year lamivudine treatment in children (n = 22) with chronic hepatitis B (CHB) who failed interferon treatment. We showed that one year lamivudine treatment resulted in decreased HBV replication and improved ALT values, but an exceptionally high rate (65%) of lamivudine-resistant mutants. Aims: The present study examined the efficacy and safety of prolonged lamivudine therapy in this group of children (aged 8.5-19 years of age). Methods: This cohort of 22 children (17 boys, 5 girls) was prospectively followed for a median of 3.6 years (range 3 to 4 years). Children were treated with lamivudine 3 mg/kg/day up to 100 mg/day, and were instructed to come back to follow up every 4 months. At each visit children underwent physical examination, compliance to treatment and side effects were recorded and blood tests were performed, including blood count, liver enzymes and bilirubin, HBeAg/antiHBe, HBV DNA and HBV mutants. Results: Of the 22 children that started the study, only five were taking lamivudine after 4 years. The reasons for drop out from the study were lack of adherence to treatment (10/17), HBeAg/antiHBe seroconversion (5/17) and lack of response to treatment (2/17). Children who maintained lamivudine treatment at the end of 4 years had persistent ALT normalization and low HBV DNA levels and YMDD mutant was present only in one child. No clinical adverse effects were recorded during lamivudine treatment or after treatment termination. Transient ALT flare up (×12 ULN) was present in one patient. Two patients showed persistent elevated CPK values (1753 IU/L to 478 IU/L) with normal blood gases and serum lactate. Conclusions: In this cohort, children with CHB who failed to respond to previous IFN therapy and were treated with lamivudine for up to 4 years, had high rates of drop out, mainly because of lack of compliance to treatment and poor HBeAg seroconversion rate, suggesting that prolonged lamivudine treatment in children is hard to achieve and probably not efficient.