Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.
Toll-like receptor(TLR)-3 gene variants may correlate with clinical significance of chronic viral infections including hepatitis B virus(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 analogues therapy.
We consecutively enrolled 127 CHB patients and 64 HBsAg-negative, anti-hepatitis C virus 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 analogues therapy.
Compare to controls, patients had a lower TLR3 mean fluorescence intensity(MFI) on PBMCs(14.61±13.49 versus 9.70±4.61,p<0.001), independent of age, gender and ALT(-13.466, 95% CI -17.202 - -9.730, p<0.001). Patients had limited TLR3 stains on Kupffer cells, controls had diffuse stains on Kupffer and hepatocytes. Hepatic TLR3 mRNA was lower in patients than controls(0.47±0.30 versus 1 fold). Using pre-treatment TLR3 MFI as referent, among five of 12 pegylated-interferon treated patients with sustained virological response(SVR), TLR3 MFI 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 ten entecavir-treated patients with on-treatment virological response, TLR3 MFI gradually restored to a mean of 1.2 folds during 48-week therapy.
CHB patients have reduced TLR3 expressions on PBMCs, independent of age, gender, ALT and on liver cells. Patients with pegylated-interferon induced SVR have a more significant restoration of TLR3 expression than those under entecavir.