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Original article

Reduced Toll-like receptor 9 expression on peripheral CD14+ 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

Corresponding author name: Sien-Sing Yang; Jia-Horng Kao
Corresponding author e-mail: jaab@cgh.org.tw; kaojh@ntu.edu.tw

Citation: Antiviral Therapy 2014; 19:637-643
doi: 10.3851/IMP2762

Date accepted: 17 December 2013
Date published online: 12 March 2014

Abstract

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.

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