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Precore wild-type DNA and immune complexes persist in chronic hepatitis B after seroconversion: no association between genome conversion and seroconversion.

Abstract
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.
AuthorsT Maruyama, S Kuwata, K Koike, S Iino, K Yasuda, H Yotsuyanagi, K Moriya, H Maekawa, H Yamada, Y Shibata, D R Milich
JournalHepatology (Baltimore, Md.) (Hepatology) Vol. 27 Issue 1 Pg. 245-53 (Jan 1998) ISSN: 0270-9139 [Print] United States
PMID9425944 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigen-Antibody Complex
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B e Antigens
Topics
  • Acute Disease
  • Adolescent
  • Adult
  • Antigen-Antibody Complex (analysis)
  • Chronic Disease
  • DNA, Viral (analysis)
  • Female
  • Genome, Viral
  • Hepatitis B Antibodies (analysis)
  • Hepatitis B e Antigens (analysis, immunology)
  • Hepatitis B virus (genetics, immunology)
  • Hepatitis B, Chronic (genetics, immunology)
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Restriction Fragment Length

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