Precore region mutation in hepatitis B virus genome in early stage of infection: a study in hepatitis B e antigen-positive young carriers.

To determine when the precore mutation at the 83rd nucleotide occurs, leading to the formation of a stop codon in the hepatitis B virus genome in carriers, which would indicate the presence of antibody to hepatitis B e antigen (anti-HBe), we investigated this mutation by direct sequencing and subcloning in 22 young hepatitis B antigen (HBeAg) (+) carriers. These subjects were 7-17 years old and were found during a survey for hepatitis B surface antigen (HBsAg) in three elementary schools, a junior high, and a senior high school. None of these carriers had clinical manifestations, although one-third of them had elevated serum alanine aminotransferase levels. All were HBeAg-positive by radioimmunoassay (RIA), and 6 of them had preserved titers of anti-HBe at the same time. Precore mutations were found in 4 subjects (18.2%), with predominance of the wild type. Although 3 of these 4 had preserved titers of HBeAb, the other had no HBeAb titers. In an other 3 subjects with preserved titers of HBeAb, the precore mutation was not detected, even after the subcloning of viral DNA. The remaining 15 subjects with HBeAg showed no precore mutation. Subjects with ALT levels exceeding 100 IU/l were all HBeAg-positive without the mutation. It was clear that the precore mutation itself occurred in the subjects at an early age during the course of infection. However, the chronological relationship between the emergence of the precore mutation and the onset of hepatitis requires further study.