Toll-like receptor and hepatitis B virus clearance in chronic infected patients: a long-term prospective cohort study in Taiwan.
J Infect Dis
; 206(5): 662-8, 2012 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-22740716
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus da Hepatite B
/
Hepatite B Crônica
/
Receptores Toll-Like
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
/
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article