Journal
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Volume 41, Issue 10, Pages 949-960Publisher
WILEY
DOI: 10.1111/apt.13170
Keywords
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Funding
- Bristol-Myers Squibb Company
- Taipei Tzu-Chi Hospital [TCRD-TPE-101-12, TCRD-TPE-103-32, TCRD-TPE-NSC-102-02]
- National Taiwan University Hospital [NTUH100-S1534]
- Department of Health [DOH99-DC-1001, DOH100-DC-1019]
- Ministry of Science and Techonology, Executive Yuan, Taiwan [NSC100-2314-B-303-012, NSC101-2314-B-303-006]
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BackgroundClearance of hepatitis B surface antigen (HBsAg) indicates clinical control of hepatitis B virus (HBV) infection. However, little is known about the impact of viral genomic variations on HBsAg loss. MethodsWe explored the association between viral genomic factors and HBsAg loss in 2121HBeAg-negative patients. HBV pre-core stop codon (1896) and basal core promoter (BCP) (1762/1764) sequences were determined in patients with HBV DNA 200IU/mL (N=1693). The effect of HBV genotype on HBsAg loss was further validated in the whole cohort of 3445 HBsAg carriers. ResultsThe cumulative lifetime (age 28-75years) incidence of HBsAg loss was 50.4% in 2121 HBeAg-negative patients. We found that genotype C, but not pre-core stop codon or BCP mutants, was associated with HBsAg loss. Compared to genotype B patients, genotype C patients had higher lifetime chance of HBsAg loss, with hazard ratio of 1.8 (95% confidence interval: 1.4-2.4). Multivariable analysis showed that male sex, elevated ALT levels, lower serum HBV DNA and HBsAg levels, and genotype C infection were associated with higher chance of HBsAg loss independently. We then performed sensitivity analysis, which re-included HBeAg-positive, cirrhotic and treatment-experienced patients, and confirmed the robustness of our results in 3445 HBsAg carriers. ConclusionGenotype C infection, compared to genotype B, is associated with a higher lifetime chance of HBsAg loss in Asian HBV carriers.
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