THE AIM of this study was to estimate the efficacy of nucleoside analogue (lamivudine) in the therapy of chronic viral hepatitis type B in children, after previous, ineffective treatment with interferon-alpha.
Patients and methods: we analyzed 53 children with chronic viral hepatitis type B, who had not responded to Interferon-alpha treatment conducted 1-7,5 years before this study (mean 4,0 +/- 7,5; median 4 years). Inclusive criteria to re-therapy with lamivudine were as follows: increased serum alanine aminotransferase activity, detected at least three times during 6 months before treatment, HBsAg and HBeAg present in the blood, viral HBV DNA detected for at least 6 months before the beginning of lamivudine therapy (above 200 genome copies per mL) and inflammation activity observed in liver biopsy specimen (biopsy performed within previous 24 months). Evaluation of side-effects of lamivudine therapy was based on anamnesis (subjective data) and laboratory tests performed regularly in the time of clinical visits during and after the end of the treatment.
Results: all the children concluded the treatment. Before lamivudine therapy, serum alanine aminotransferase activity ranged between 20-590 IU/L. In 28,4% of children it was less than 100 IU/L. In almost all the children moderate staging and grading were observed in liver biopsy specimens. HBV DNA in serum ranged between 200-200000 copies/mL: in 31 children (58,4%) HBV DNA exceeded 200000 copies/mL, in 5 (28,3%) was between 10000 and 200000 copies/mL, and in 7 (13,2% ) was below 10000 copies/mL. Applied treatment resulted in alanine aminotransferase activity normalization in 79,2% of children, mostly after 2-11 months (mean 3,9 +/- 2,7; median 3,8 months). HBeAg/HBeAb seroconversion was achieved in 28,3% of children, usually at the end of lamivudine therapy (approximately after 12 months). Sustained viral response was observed in 24,5% of treated children. There were no undesirable effects of therapy noted. Serum alanine aminotransferase activity increased slightly and temporarily in 4 children between 3rd and 12th month of therapy. In 2 of these children YMDD mutation was detected.
Conclusions: lamivudine is effective, safe and well tolerated in treatment of chronic viral hepatitis type B, following unsuccessful interferon-alpha therapy. Serum alanine aminotransferase activity normalized in most of the patients. HBeAg/HBeAb seroconversion as well as positive viral response is mostly connected with low level of HBV DNA before therapy.