Does genotype predict response to treatment in children infected with hepatitis B perinatally?

Abstract

HBV genotype may correlate with outcome and treatment response. Genotype has been compared with treatment response in children infected perinatally with hepatitis B following treatment with oral antiviral drugs (lamivudine or adefovir) or interferon (IFN) alone and with prednisolone priming (Pred/IFN). All children who took part in clinical trials in this unit since 1990 were included. Hepatitis B genotypes were determined by direct sequencing or using a commercial line probe assay (InnoLipa). Sixty-five children were included; 20 were treated with IFN; 19 with Pred/IFN; 22 with lamivudine and 7 with adefovir, some took part in more than one treatment study. 63 out of 65 children were clearly typed into single genotypes; 16, 7, 3, and 37 typing as A, B, C, and D respectively. The majority of South-Asian children had genotype D and European and Afro-Caribbean children were more likely to have genotype A. Treatment response (seroconversion from HBeAg to Anti-HBe) was better in children with genotypes A [n = 16] and D [n = 37] (55.5% and 48.7%), compared to those with B [n = 7] and C [n = 3] (12.5% and 0%) for all treatments. The response to interferon alone was better in children with genotype A compared to D (50% and 36%), but prednisolone priming improved the response so that there was no difference between genotypes A and D (66.7% and 70%). Assessment of genotype in children pre-treatment may provide a guide to potential response. The response to treatment by genotype should be evaluated in future clinical trials in children.