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- Title
Toll-like Receptor and Hepatitis B Virus Clearance in Chronic Infected Patients: A Long-Term Prospective Cohort Study in Taiwan.
- Authors
Wu, Jia-Feng; Chen, Chien-Hung; Ni, Yen-Hsuan; Lin, Ying-Ting; Chen, Huey-Ling; Hsu, Hong-Yuan; Chang, Mei-Hwei
- Abstract
Background.We sought to elucidate the impacts of the Toll-like receptors (TLRs) on spontaneous hepatitis B virus (HBV) e antigen (HBeAg) and hepatitis B s antigen (HBsAg) seroconversion in chronic HBV-infected patients.Methods.Human TLR2, TLR4, TLR5, and TLR9 gene polymorphisms were assessed in 278 HBeAg-positive, chronic HBV-infected patients. Additionally, HBV core antigen (HBcAg) in vitro stimulation using peripheral blood mononuclear cells (PBMCs) from 113 patients was done to assess interferon γ (IFN- γ) production.Results.Of the study subjects, 204 (73.4%) developed spontaneous HBeAg seroconversion, 21 (7.6%) developed spontaneous HBsAg clearance, and 10 (3.6%) had spontaneous HBsAg seroconversion during the 19.1 ± 9.9 years of follow-up. The T allele at TLR5 rs5744174 (p.Phe616Leu) and the C allele at TLR9 rs5743836 promoter predicted earlier HBeAg seroconversion (hazard ratios [HRs], 2.45 and 3.65; P = .04, and .006, respectively). The TLR5 rs5744174 T allele carriers have higher PBMCs IFN-γ secretion to HBcAg stimulation (P= .0002). The G allele carriers at TLR4 rs4986790 (p.Asp299Gly) predicted spontaneous HBsAg seroclearance (HR, 18.73; P < .001) and seroconversion (HR, 43.45; P < .001).Conclusions.Toll-like receptor 5 rs5744174 (p.Phe616Leu) and TLR9 rs5743836 promoter area polymorphism were associated with earlier spontaneous HBeAg seroconversion. Toll-like receptor 4 rs4986790 (p.Asp299Gly) was associated with HBsAg seroclearance/seroconversion in chronic HBV patients. Toll-like receptor 5 rs5744174 (p.Phe616Leu) was associated with higher IFN-γ production in chronic HBV-infected patients.
- Subjects
TAIWAN; TOLL-like receptors; HEPATITIS B virus; COHORT analysis; GENETIC polymorphisms; INTERNAL medicine
- Publication
Journal of Infectious Diseases, 2012, Vol 206, Issue 5, p662
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jis420