We prospectively studied the
HBsAg seroconversion with sequential combination
therapy of
lamivudine (
LAM) and
interferon (IFN) in hitherto untreatable 'immune-tolerant'
chronic hepatitis B in children. In this case-control study, 28 children with immune-tolerant
hepatitis B [
HBsAg positive for >6 months with near normal
aminotransferase level, minimal/no
inflammation in liver histology and high viral load (HBV
DNA>10(7) copies/mL)] were treated with
LAM alone at 3 mg/kg/day for 8 weeks followed by
LAM plus IFN alpha (5 MU/m(2) three times a week) for another 44 weeks. They were compared with 34 untreated children. HBV markers (
HBsAg,
HBeAg, anti-HBe, quantitative HBV
DNA) were carried out at baseline, at the end of
therapy and 6 monthly thereafter. The mean age was 5.9 ± 3.2 years and 24 were boys. End
therapy response: HBe seroconversion was achieved in 11, and of these, five had complete response (
HBsAg clearance), 11 did not respond and six had virologic response (
DNA undetectable but no HBe seroconversion). Six months after
therapy, 10 of the 11 (91%) originally seroconverted children remained seroconverted while one seroreverted. Six of the 28 (21.4%) children lost
HBsAg and they remained
HBsAg negative and anti-HBs positive on follow-up. After a mean follow-up of 21.1 ± 11.9 months, the status remained same in the responders but one of the nonresponders HBe seroconverted (39.3%). There were no serious side effects of
therapy. It is possible to achieve a cure in more than one-fifth of immune-tolerant children with
hepatitis B with the sequential combination of
LAM and IFN.