Precore wild-type DNA and immune complexes persist in chronic hepatitis B after seroconversion: no association between genome conversion and seroconversion.
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.
Maruyama
T
T
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Kuwata
S
S
Koike
K
K
Iino
S
S
Yasuda
K
K
Yotsuyanagi
H
H
Moriya
K
K
Maekawa
H
H
Yamada
H
H
Shibata
Y
Y
Milich
D R
DR
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000936:Antigen-Antibody Complex / Q000032:analysis*; D002908:Chronic Disease; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D016679:Genome, Viral; D006510:Hepatitis B Antibodies / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length
D000936:Antigen-Antibody Complex; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens