Reduced toll-like receptor 9 expression on peripheral C D14+ monocytes of chronic hepatitis B patients and its restoration by effective therapy

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

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Background: Chronic hepatitis B (CHB) patients display Toll-like receptor 9 (TLR9)-dependent defective immune responses. We aimed to study TLR9 expression on CHB patients and its alteration during therapy.

Methods: We compared TLR9 expression on fresh peripheral CD14+ monocytes from a cohort of 97 CHB patients and 35 HBsAg-negative, anti-HCV-negative controls, during pegylated interferon or entecavir therapy. TLR9 expression on liver tissue was also investigated.

Results: Compared with controls, peripheral CD14+ monocytes of CHB patients displayed reduced expression of TLR9 mean fluorescence intensity (MFI; 9.90 ±3.64 versus 7.95 ±3.61; P=0.007) independent of age, gender and alanine aminotransferase (ALT; -2.09, 95% CI -3.568, -0.613; P=0.006). Furthermore, age, gender, ALT, HBeAg status, quantitative HBsAg (qHBsAg) or HBV DNA did not predict the TLR9 expression (P=0.863). Hepatic TLR9 messenger RNA (mRNA) was significantly reduced in 54 patients compared with 3 controls (0.45 ±0.32 versus 1-fold). Using response-guided therapy by qHBsAg levels and pretreatment TLR9 MFI as a reference, TLR9 MFI restored to a mean of 1.7-to 2.7-fold in pegylated interferon responders and reduced to a mean of 0.6-to 0.7-fold in non-responders starting from treatment week 12. Among 10 entecavir-treated patients, TLR9 MFI gradually restored to a mean of 1.2-to 2.1-fold starting from treatment week 48.

Conclusions: CHB patients display reduced TLR9 expression on peripheral CD14+ monocytes, which is independent of host and viral markers, and on liver tissue. Responders to pegylated interferon and those under entecavir demonstrate restoration of TLR9 expression. On-treatment TLR9 expression on peripheral monocytes might predict response to pegylated interferon therapy.

Original languageEnglish
Pages (from-to)637-643
Number of pages7
JournalAntiviral Therapy
Issue number7
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases


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