Cure for immune‐tolerant hepatitis B in children: is it an achievable target with sequential combo therapy with lamivudine and interferon?

Summary We prospectively studied the HB s A g 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 [ HB s A g 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 ( HB s A g, HB e A g, anti‐ HB e, 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: HB e seroconversion was achieved in 11, and of these, five had complete response ( HB sAg clearance), 11 did not respond and six had virologic response ( DNA undetectable but no HB e 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 HB s A g and they remained HB s A g negative and anti‐ HB s 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 HB e 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 .