Journal article
Quantitative dynamics of hepatitis B basal core promoter and precore mutants before and after HBeAg seroconversion
Journal of hepatology, v 56(4), pp 795-802
Apr 2012
PMID: 22173170
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
Using our novel mutant quantification methods, the percentage of the mutant viruses was analyzed both cross-sectionally and longitudinally, before and after seroconversion.
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%.
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.
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Details
- Title
- Quantitative dynamics of hepatitis B basal core promoter and precore mutants before and after HBeAg seroconversion
- Creators
- Hui Nie - Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, USAAlison A Evans - School of Public Health, Drexel University, Philadelphia, PA, USAW. Thomas London - Fox Chase Cancer Center, Philadelphia, PA, USATimothy M Block - Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, USAXiangdong David Ren - Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, USA
- Publication Details
- Journal of hepatology, v 56(4), pp 795-802
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Epidemiology and Biostatistics
- Web of Science ID
- WOS:000302272600009
- Scopus ID
- 2-s2.0-84858698728
- Other Identifier
- 991014878295304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Gastroenterology & Hepatology