Precore hepatitis B virus (HBV) mutants may gradually prevail during or after seroconversion (SC) from
hepatitis B e antigen (
HBeAg) to
hepatitis B e antigen antibody (anti-HBe) status in many
chronic hepatitis B (CH-B) patients. However, patients with CH-B still produce anti-HBe more than several years after SC, and the relationship between SC and genome conversion in the precore region has not been clarified. Therefore, in patients with CH-B who had a sustained loss of
HBeAg and complete remission of
hepatitis after SC, the precore region was sequenced in paired serum samples from 1 year before SC to 3 years after SC. Mutant precore defective HBV
DNA was found in only 6 (19%) of 31 CH-B patients who had a complete remission of
hepatitis after SC. Mixed-type HBV
DNA (precore wild-type and mutant-type) was found in 4 (13%) patients. Wild-type HBV
DNA was found in 21 (68%) CH-B patients after SC. Longer-term follow-up of 11 CH-B patients indicated that 3 of 11 patients experienced precore genome conversion 2 to 3 years after SC. E-plus
DNA or e-minus
DNA was semiquantitated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays before and after SC. E-plus
DNA levels decreased from 10(5.56+/-1.58) to 10(2.45+/-1.61). Similarly, e-minus
DNA levels declined from 10(4.25+/-1.56) to 10(1.86+/-1.37). By dot-blot assay, serum HBV
DNA became negative soon after SC, as did serum
HBeAg. In contrast,
HBeAg-containing
immune complexes were still detected after SC. Anti-HBe antibody was produced throughout SC and thereafter, as determined by a sensitive experimental assay. Therefore, we conclude that genome-conversion in the precore region is a separate event from
HBeAg/anti-HBe seroconversion.