title: Toll-like receptor and hepatitis B virus clearance in chronic infected patients: a long-term prospective cohort study in Taiwan.
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.
authors: Department of Pediatrics, National Taiwan University Hospital, Taipei.
authors: Jia-Feng
authors: JF
authors: Wu
authors: Chien-Hung
authors: CH
authors: Chen
authors: Yen-Hsuan
authors: YH
authors: Ni
authors: Ying-Ting
authors: YT
authors: Lin
authors: Huey-Ling
authors: HL
authors: Chen
authors: Hong-Yuan
authors: HY
authors: Hsu
authors: Mei-Hwei
authors: MH
authors: Chang
mesh_terms: D002648:Child; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000821:virology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011863:Radioimmunoassay; D013624:Taiwan; D051193:Toll-Like Receptors / Q000096:biosynthesis* / Q000235:genetics; D019562:Viral Load
chemical_list: D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D051193:Toll-Like Receptors; D004247:DNA