降低Toll样受体3的表达慢性乙型肝炎患者，其恢复干扰素治疗

StephenW

Antivir Ther. 2013;18(7):877-84. doi: 10.3851/IMP2630. Epub 2013 Jun 6.
Reduced Toll-like receptor 3 expression in chronic hepatitis B patients and its restoration by interferon therapy.
Huang YW, Lin SC, Wei SC, Hu JT, Chang HY, Huang SH, Chen DS, Chen PJ, Hsu PN, Yang SS, Kao JH.
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Abstract
BACKGROUND:

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.
METHODS:

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.
RESULTS:

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.
CONCLUSIONS:

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.

StephenW

小红疗法。 2013 ， 18 （ 7 ） :877- 84 。 DOI ： 10.3851/IMP2630 。 epub的2013 6月6日。
降低Toll样受体3的表达慢性乙型肝炎患者，其恢复干扰素治疗。
黄雯，林SC ， SC伟，胡JT ，张晔，黄SH，陈德尚，陈丕基，许PN ，杨SS ，高JH 。
作者信息
摘要
背景：

Toll样受体（ TLR ） 3的基因变异可能与相关慢性病毒感染，包括乙肝病毒的临床意义。我们旨在探讨TLR3的外周血单个核细胞（PBMC ），慢性乙型肝炎（CHB ）患者和其对聚乙二醇干扰素或核苷类似物治疗的肝细胞中的表达和。
方法：

我们连续参加127 CHB患者和64乙肝表面抗原阴性，抗-HCV阴性的健康人作为对照。我们比较了从患者和对照新鲜外周血单个核细胞和肝细胞的TLR3的表达，之前和期间聚乙二醇干扰素或核苷类似物治疗。
结果：

与对照组相比，患者有较低的TLR3的平均荧光强度（MFI ）的外周血单个核细胞（平均值±标准差14.61 ± 13.49与9.70 ± 4.61 ，P < 0.001 ） ，与年龄，性别和丙氨酸氨基转移酶（ ALT ， -13.466 ， 95 ％ CI为-17.202 ， -9.730 ，P < 0.001 ） 。患者曾在枯否细胞TLR3有限的污渍，而对照组的肝巨噬细胞和肝细胞弥漫性污渍。肝TLR3信使RNA降低患者比对照组（ 0.47 ±0.30与1倍）。使用预处理TLR3小额信贷机构作为一种指涉，其中5 12聚乙二醇干扰素治疗的患者持续病毒学应答（SVR ）的， TLR3 MFI恢复到平均为1.5到治疗后1.7折。在七个无应答或复发者， TLR3小额信贷机构降低到平均为0.5到0.7倍。其中10恩替卡韦治疗的患者对治疗的病毒学应答， TLR3小额信贷机构逐渐已于48周的治疗恢复到平均为1.2倍。
结论：

CHB患者减少了对外周血单个核细胞，不受年龄，性别和ALT ，并在肝细胞TLR3表达。患者聚乙二醇干扰素诱导的SVR有更显著的恢复TLR3的表达比在恩替卡韦。