臺大醫院-小兒部;臺大醫院-內科部;JIA-FENG WUCHIEN-HUNG CHENYEN-HSUAN NILin, Ying-TingYing-TingLinHUEY-LING CHENHONG-YUAN HSUMEI-HWEI CHANG2018-09-102018-09-102012http://www.scopus.com/inward/record.url?eid=2-s2.0-84864955687&partnerID=MN8TOARShttp://scholars.lib.ntu.edu.tw/handle/123456789/369355Background.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 (IFN-) 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-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-production in chronic HBV-infected patients. ? The Author 2012.103 bytestext/html[SDGs]SDG3gamma interferon; hepatitis B core antigen; hepatitis B surface antigen; hepatitis B(e) antigen; toll like receptor 2; toll like receptor 4; toll like receptor 5; toll like receptor 9; adolescent; adult; allele; article; child; cohort analysis; controlled study; cytokine production; cytokine release; female; follow up; gene; genotype; hepatitis B; Hepatitis B virus; heterozygote; human; human cell; major clinical study; male; nonhuman; peripheral blood mononuclear cell; preschool child; priority journal; promoter region; prospective study; seroconversion; single nucleotide polymorphism; Taiwan; toll like receptor 2 gene; toll like receptor 4 gene; toll like receptor 5 gene; toll like receptor 9 gene; viral clearance; virus load; Child; Cohort Studies; DNA; Female; Genetic Variation; Genotype; Hepatitis B Core Antigens; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Logistic Models; Male; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Prospective Studies; Radioimmunoassay; Taiwan; Toll-Like Receptors; Viral Loadjournal article10.1093/infdis/jis420