Toll-like Receptor and Hepatitis B Virus Clearance in Chronic Infected Patients: A Long-Term Prospective Cohort Study in Taiwan

• Published in: The Journal of infectious diseases Vol. 206; no. 5; pp. 662 - 668
• Main Authors: Wu, Jia-Feng, Chen, Chien-Hung, Ni, Yen-Hsuan, Lin, Ying-Ting, Chen, Huey-Ling, Hsu, Hong-Yuan, Chang, Mei-Hwei
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2012
• Subjects: Alleles; Biological and medical sciences; Child; Chronic hepatitis; Cohort Studies; DNA - chemistry; DNA - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic Variation; Genotype; Genotypes; Hepatitis antigens; Hepatitis B; Hepatitis B Core Antigens - blood; Hepatitis B e Antigens - blood; Hepatitis B Surface Antigens - blood; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - isolation & purification; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - virology; Humans; Infections; Infectious diseases; Logistic Models; Male; Medical sciences; Microbiology; Miscellaneous; P values; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Prospective Studies; Radioimmunoassay; Referents; Taiwan; Toll like receptors; Toll-Like Receptors - biosynthesis; Toll-Like Receptors - genetics; Viral Load; Virology; VIRUSES; Asia; Taiwan; Far east; Virus; Human; Infection; Subtropical zone; Chronic; Hepadnaviridae; Cohort study; Orthohepadnavirus; Toll like receptor; Hepatitis B virus
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jis420

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, TLR5y 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 serodearance/seroconversion in chronic HBV patients. Toll-like receptor 5 rs5744174 (p. Phe616Leu) was associated with higher IFN-γ production in chronic HBV-infected patients.