Advanced periductal fibrosis from infection with the carcinogenic human liver fluke Opisthorchis viverrini correlates with elevated levels of interleukin-6.
Advanced periductal fibrosis from infection with the carcinogenic human liver fluke Opisthorchis viverrini correlates with elevated levels of interleukin-6.
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DOI：
10.1002/hep.23134
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发表时间：
2009-10
期刊：
影响因子：
13.5
通讯作者：
Bethony, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Sripa, Banchob;Mairiang, Eimorn;Thinkhamrop, Bandit;Laha, Thewarach;Kaewkes, Sasithorn;Sithithaworn, Paiboon;Tessana, Smarn;Loukas, Alex;Brindley, Paul J.;Bethony, Jeffrey M.
超过7.5亿人有感染食源性肝吸虫的危险。由于其与胆管癌（CCA）密切相关，因此被认为是这些寄生虫中最重要的一种。弧菌感染导致宿主慢性炎症，可导致晚期、病原体特异性疾病的后遗症，包括阻塞性黄疸、肝肿大、胆囊炎和CCA。然而，在疾病的后遗症出现之前，重要的肝脏炎症变化可以在感染O. viverrini期间早期检测到。在一项病例对照研究中，研究人员对328名感染弧菌的男性和女性进行了研究，确定了无症状弧菌感染个体是否存在晚期管周纤维化，然后测量了细胞因子对弧菌排泄/分泌产物（ES）的反应。在200名患有晚期管周纤维化的参与者（病例）中，白细胞介素(IL)-6至O. viverrini ES的水平比128名没有晚期管周纤维化的O. viverrini感染个体（对照组）的水平高8倍。此外，在性别和年龄调整后的模型中，IL-6对ES寄生虫的升高与晚期管周纤维化的风险增加63%相关。研究还发现，随着IL-6水平的升高，晚期管周纤维化的风险也会增加：IL-6- es分泌量第三四分位数的个体发生晚期管周纤维化的风险比IL-6分泌量第一四分位数的个体高127%。患有晚期管周纤维化的弓形虫感染个体表现出其他肝胆异常，包括胆囊收缩性降低和胆囊污泥的存在。这些数据强烈暗示寄生虫特异性IL-6在胆管病晚期管周纤维化发病机制中的作用，并可能与其他肝胆异常有关，包括胆管癌。
More than 750 million people are at risk of infection with food-borne liver flukes. Opisthorchis viverrini is considered among the most important of these parasites, due to its strong association with cholangiocarcinoma (CCA). O. viverrini infection results in a chronic inflammatory challenge to the host, which can lead to advanced, pathogen-specific disease sequelae including obstructive jaundice, hepatomegaly, cholecystitis, as well as CCA. However, before disease sequelae are apparent, important inflammatory changes to the liver can be detected early during O. viverrini infection. In a case-control study involving 328 men and women with O. viverrini infection, we determined the presence of advanced periductal fibrosis in asymptomatic, O. viverrini-infected individuals and then measured cytokine responses to O. viverrini excretory/secretory products (ES). In the 200 participants with advanced periductal fibrosis (cases), levels of Interleukin (IL)-6 to O. viverrini ES were 8 times higher than levels of the 128 O. viverrini-infected individuals without advanced periductal fibrosis (controls). Moreover, elevated IL-6 to parasite ES was associated with increased risk of advanced periductal fibrosis by 63% in a model adjusted for sex and age. The risk of advanced periductal fibrosis was also found to increase with higher levels of IL-6: individuals in the third quartile of IL-6-ES production had a 127% higher risk of developing advanced periductal fibrosis than individuals in the first quartile of IL-6 production. O. viverrini-infected individuals with advanced periductal fibrosis showed other hepatobiliary abnormalities, including reduced gallbladder contractility and the presence of gallbladder sludge. These data strongly implicate a role for parasite specific IL-6 in the pathogenesis of advanced periductal fibrosis in opisthorchiasis, with possible links to other hepatobiliary abnormalities, including cholangiocarcinoma.
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