Huang Yi-Wen, Lin Shih-Chang, Wei Shu-Chen, Hu Jui-Ting, Chang Han-Yu, Huang Shih-Hung, Chen Ding-Shinn, Chen Pei-Jer, Hsu Ping-Ning, Yang Sien-Sing, Kao Jia-Horng
Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.
Antivir Ther. 2013;18(7):877-84. doi: 10.3851/IMP2630. Epub 2013 Jun 6.
Toll-like receptor (TLR)3 gene variants may correlate with clinical significance 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.
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.
Compared to controls, patients had a lower TLR3 mean fluorescence 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.
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 significant restoration of TLR3 expression than those under entecavir.
Toll样受体（TLR）3基因变异可能与包括HBV在内的慢性病毒感染的临床意义相关。我们旨在研究慢性乙型肝炎（CHB）患者外周血单个核细胞（PBMC）和肝细胞中TLR3的表达及其对聚乙二醇干扰素或核苷类似物治疗的反应。
我们连续纳入了127例CHB患者和64例乙型肝炎表面抗原阴性、抗-HCV阴性的健康个体作为对照。我们比较了患者和对照在聚乙二醇干扰素或核苷类似物治疗前及治疗期间新鲜PBMC和肝细胞上的TLR3表达。
与对照相比，患者PBMC上的TLR3平均荧光强度（MFI）较低（平均值±标准差14.61±13.49对9.70±4.61；P<0.001），与年龄、性别和丙氨酸氨基转移酶（ALT）无关（-13.466，95%可信区间-17.202，-9.730；P<0.001）。患者肝巨噬细胞上的TLR3染色有限，而对照在肝巨噬细胞和肝细胞上有弥漫性染色。患者肝脏TLR3信使核糖核酸低于对照（0.47±0.30对1倍）。以治疗前TLR3 MFI为参照，在12例接受聚乙二醇干扰素治疗且获得持续病毒学应答（SVR）的患者中，有5例在治疗后TLR3 MFI立即恢复至平均1.5至,1.7倍。在7例无应答者或复发者中，TLR3 MFI降至平均0.5至0.7倍。在10例接受恩替卡韦治疗且获得治疗期病毒学应答的患者中，TLR3 MFI在48周治疗期间逐渐恢复至平均1.2倍。
CHB患者PBMC及肝细胞上的TLR3表达降低，与年龄、性别和ALT无关。聚乙二醇干扰素诱导获得SVR的患者比接受恩替卡韦治疗的患者TLR3表达恢复更显著。
