Sequence variation of hepatitis B virus precore-core open reading frame isolated from serum and liver of children with chronic hepatitis B before andafter interferon treatment

DNA and amino acid sequences of the hepatitis B virus (HBV) genome were stu died in serum and liver samples taken from 12 children with chronic hepatit is B before and after interferon (IFN) therapy. The purpose was to discover whether the persistence of low levels of viral replication with normal ala nine aminotransferases after the response to IFN treatment is due to the ap pearance of mutations in the sequence of HE core antigen T and B cell epito pes. The existence of mutants was studied by amplification of precore-core region of the HBV genome by polymerase chain reaction (PCR) and direct sequ encing of the PCR products. In addition to the wild type sequence, mutation 1896 in the precore region was detected in the baseline serum and liver sa mples of five children. No changes in the distribution were found in the fi nal samples, except one case. In the core region, both the wild type sequen ce and amino acid substitutions were observed in the basal serum and/or liv er samples of six patients and most of these remained detectable in the sam ples after treatment. Sixteen (67%) of 24 changes in the core amino acid se quences were found in the T- or B-cell epitopes. The results suggest that v iral persistence after response to IFN therapy in children is not due to th e appearance of mutants in the HBV core T- and B-cell epitopes and that the host immune response can control the viral replication. (C) 1999 Wiley-Lis s, Inc.