Reduced toll-like receptor 9 expression on peripheral C D14+ monocytes of chronic hepatitis B patients and its restoration by effective therapy
Journal
Antiviral Therapy
Journal Volume
19
Journal Issue
7
Pages
637-643
Date Issued
2014
Author(s)
Hsu C.-K.
Lin S.-C.
Hu J.-T.
Chang H.-Y.
Liang C.-W.
Yang S.-S.
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. ? 2014 International Medical Press.
SDGs
Other Subjects
alanine aminotransferase; CD14 antigen; entecavir; hepatitis B surface antigen; hepatitis B(e) antigen; messenger RNA; peginterferon; toll like receptor 9; virus DNA; alpha interferon; antivirus agent; CD14 antigen; entecavir; guanine; toll like receptor 9; adult; age distribution; aged; Article; cohort analysis; controlled study; drug response; female; gender; gene expression; hepatitis B; human; human cell; human tissue; major clinical study; male; monocyte; prospective study; protein expression; treatment outcome; analogs and derivatives; case control study; Hepatitis B, Chronic; immunology; liver; metabolism; middle aged; monocyte; virus load; Adult; Antigens, CD14; Antiviral Agents; Case-Control Studies; DNA, Viral; Female; Guanine; Hepatitis B, Chronic; Humans; Interferon-alpha; Liver; Male; Middle Aged; Monocytes; Prospective Studies; Toll-Like Receptor 9; Treatment Outcome; Viral Load
Publisher
International Medical Press Ltd
Type
journal article