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 (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