Age at Time of Hepatitis Be Antibody Seroconversion in Childhood Chronic Hepatitis B Infection and Mutant Viral Strain Detection Rates

Abstract

Investigations of adult patients have demonstrated that with seroconversion, changes occur from wild-type strains of the infecting virus to mutant strains. However, to date, there have been few reports and insufficient investigation of this issue in children. The presence or absence of nucleotide base and amino acid sequence mutations in a portion of the X region containing the core promoter region, the pre-C region, and the C region of HBV genomic DNA were investigated using a polymerase chain reaction-direct sequencing method on serum samples collected from 14 children who were hepatitis Be antibody (HBeAb)-positive carriers. Samples from three children who were HBe antigen (HBeAg)-positive carriers served as the control subjects. When patients were grouped based on whether they had had documented seroconversion before age 6 or at age 6 or older, differences in mutant viral detection rates involving the core promoter region and the pre-C region were apparent. Specifically, a mutant strain showing a G-to-A substitution at nucleotide 83 in the pre-C region, or a mutant strain showing an A-to-T substitution at nucleotide 1762 and a G-to-A substitution at nucleotide 1764, was detected in only two of eight cases (25%) from the HBeAb-positive carriers with documented seroconversion before age 6. In contrast, these findings were present in six of six patients (100%) with documented seroconversion at age 6 or older. The results of the present study suggest that the mechanism of onset of HBeAb seroconversion differs between children aged less than 6 years and those who are aged 6 or more.