Reduced Toll-like receptor 3 expression in chronic hepatitis B patients and its restoration by interferon therapy

Yi Wen Huang, Shih Chang Lin, Shu Chen Wei, Jui Ting Hu, Han Yu Chang, Shih Hung Huang, Ding Shinn Chen, Pei Jer Chen, Ping Ning Hsu, Sien Sing Yang, Jia Horng Kao

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Background: Toll-like receptor (TLR)3 gene variants may correlate with clinical signiicance of chronic viral infections including HBV. We aimed to investigate the expression of TLR3 in peripheral blood mononuclear cells (PBMCs) and liver cells of chronic hepatitis B (CHB) patients and its response to pegylated interferon or nucleoside analogue therapy. Methods: We consecutively enrolled 127 CHB patients and 64 hepatitis B surface antigen-negative, anti-HCV-negative healthy individuals as controls. We compared the TLR3 expressions on fresh PBMCs and liver cells from patients and controls, before and during pegylated interferon or nucleoside analogue therapy. Results: Compared to controls, patients had a lower TLR3 mean luorescence intensity (MFI) on PBMCs (mean ±SD 14.61 ±13.49 versus 9.70 ±4.61; P<0.001), independent of age, gender and alanine aminotransferase (ALT; -13.466, 95% CI -17.202, -9.730; P<0.001). Patients had limited TLR3 stains on Kupffer cells, whereas controls had diffuse stains on Kupffer and hepatocytes. Hepatic TLR3 messenger RNA was lower in patients than controls (0.47 ±0.30 versus 1-fold). Using pretreatment TLR3 MFI as a referent, among 5 of 12 pegylated-interferon-treated patients with sustained virological response (SVR), TLR3 MFI was restored to a mean of 1.5- to 1.7-folds immediately after treatment. Among seven non-responders or relapsers, TLR3 MFI reduced to a mean of 0.5- to 0.7-fold. Among 10 entecavir-treated patients with on-treatment virological response, TLR3 MFI gradually was restored to a mean of 1.2-folds during 48-week therapy. Conclusions: CHB patients have reduced TLR3 expression on PBMCs, independent of age, gender and ALT, and on liver cells. Patients with pegylated-interferon-induced SVR have a more signiicant restoration of TLR3 expression than those under entecavir.

Original languageEnglish
Pages (from-to)877-884
Number of pages8
JournalAntiviral Therapy
Volume18
Issue number7
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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