| Quantitative dynamics of hepatitis B basal core promoter and precore mutants before and after HBeAg seroconversion. | |
MedLine Citation:
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PMID: 22173170 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND & AIMS: Hepatitis B e antigen (HBeAg) seroconversion is an important clinical and virological "landmark" during chronic hepatitis B virus (HBV) infection. Mutant viruses carrying the precore G1896A and/or the basal core promoter (BCP) A1762T/G1764A mutations are associated with HBeAg seroconversion. However, the exact role of these mutants in HBeAg seroconversion remains unclear, partly because the evolution of these mutant viruses before and after seroconversion has not been well studied. METHODS: Using our novel mutant quantification methods, the percentage of the mutant viruses was analyzed both cross-sectionally and longitudinally, before and after seroconversion. RESULTS: Cross-sectional analysis showed that the percentage of both precore and BCP mutants gradually increased with age in the HBeAg-positive population. Follow-up of 18 HBeAg-positive patients revealed that the mutant percentage may stay low and stable for many years, followed by a steady increase in the percentage of G1896A and/or A1762T/G1764A mutants, from <10% to 50-100%, within about 3 years prior to seroconversion. In all cases, increase of mutant percentage was preceded or accompanied by elevated serum alanine aminotransferase. After the seroconversion, the mutant percentage could remain high or decrease significantly, sometimes to below 20%. CONCLUSIONS: Levels of G1896A and A1762T/G1764A mutants (of genotypes B and C) in the HBeAg-positive patients may predict the time of HBeAg seroconversion. The dominance of these mutants in the HBeAg-positive phase is more likely the result of immune selection rather than the enhanced replication capability of the mutants. However, anti-HBe antibody may not be a major selection force for these mutants. |
Authors:
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Hui Nie; Alison A Evans; W Thomas London; Timothy M Block; Xiangdong David Ren |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-12-13 |
Journal Detail:
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Title: Journal of hepatology Volume: 56 ISSN: 1600-0641 ISO Abbreviation: J. Hepatol. Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-03-19 Completed Date: 2012-09-11 Revised Date: 2014-09-24 |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: England |
Other Details:
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Languages: eng Pagination: 795-802 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Alanine Transaminase / blood Child Child, Preschool Cross-Sectional Studies DNA, Viral / blood Follow-Up Studies Genotype Hepatitis B e Antigens / blood*, immunology Hepatitis B virus / genetics*, immunology Hepatitis B, Chronic / blood, genetics*, immunology* Humans Infant Longitudinal Studies Middle Aged Mutation / genetics* Predictive Value of Tests Promoter Regions, Genetic / genetics* Viral Core Proteins / genetics* Viral Load Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA136607/CA/NCI NIH HHS; U01 CA084951/CA/NCI NIH HHS; U01 CA084951-10/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Viral; 0/Hepatitis B e Antigens; 0/Viral Core Proteins; EC 2.6.1.2/Alanine Transaminase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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