Elevated liver stiffness is linked to increased biomarkers of inflammation and immune activation in HIV/hepatitis C virus-coinfected patients
Elevated liver stiffness is linked to increased biomarkers of inflammation and immune activation in HIV/hepatitis C virus-coinfected patients
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DOI：
10.1097/qad.0000000000001787
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发表时间：
2018-06-01
期刊：
影响因子：
3.8
通讯作者：
Resino, Salvador
中科院分区：
文献类型：
--
作者：
Medrano, Luz M.;Garcia-Broncano, Pilar;Resino, Salvador
目的：免疫失调是HIV和丙型肝炎病毒（HCV）感染的标志。我们的目的是评估肝硬度测量（LSM）与HIV/ hcv合并感染患者的t细胞活化、细菌易位、炎症、内皮功能障碍和凝血功能障碍的生物标志物之间的关系。设计：横断面研究。方法：238例HIV/ hcv合并感染患者，32例健康对照，39例HIV-单感染患者。根据LSM分为小于12.5、12.5-25、25-40、大于40 kPa四组。t细胞亚群采用流式细胞术测定，血浆生物标志物采用免疫分析法测定。结果:HIV/ hcv共感染患者外周血免疫激活[t细胞激活(CD4(+)CD38（+）和CD8(+)CD38(+)]、细菌易位（可溶性CD14）、炎症[IL-1b、IL-6、IL-8、IL-18、ifn - γ诱导蛋白10 (IP-10)]、内皮功能障碍[可溶性血管细胞粘附分子1 （sVCAM1）、可溶性细胞间细胞粘附分子1 （sICAM1）和可溶性肿瘤坏死因子受体1 (sTNFR1)]水平较高。和凝血功能障碍（纤溶酶原激活物抑制剂-1）]。此外，在HIV/ hcvco感染患者中，LSM与免疫激活[t细胞激活(CD8(+)CD38（+）细菌易位（脂多糖），炎症（IL8, IP-10），内皮功能障碍（sVCAM1， sICAM1和sTNFR1）和凝血功能障碍（d -二聚体）]之间存在直接关系。随后，将患者分层到不同的纤维化阶段，发现LSM≥40 kPa的肝硬化患者在免疫激活[t细胞激活(CD4(+)CD38（+）和CD8（+)CD38(+)）、细菌易位（脂多糖）、炎症（IL-8、IL-6、IP-10）、内皮功能障碍（sVCAM1、sICAM1和sTNFR1）和凝血功能障碍（Ddimer）]方面的生物标志物值高于其他三组患者（< 12.5、12.5-25和25-40 kPa）。结论：t细胞活化、细菌易位、炎症、内皮功能障碍和凝血功能障碍随着HIV/HCV合并感染患者肝纤维化的严重程度而增加，尤其是LSM≥40kpa的患者。版权所有2018威科集团有限公司版权所有。
Objectives: Immune dysregulation is a hallmark of HIV and hepatitis C virus (HCV) infections. We aimed to evaluate the relationship between liver stiffness measurement (LSM) and biomarkers of T-cell activation, bacterial translocation, inflammation, endothelial dysfunction, and coagulopathy in HIV/HCV-coinfected patients.Design: Cross-sectional study.Methods: We studied 238 HIV/HCV-coinfected patients, 32 healthy controls, and 39 HIV-monoinfected patients. Patients were stratified according to LSM into four groups: less than 12.5, 12.5-25, 25-40, and more than 40 kPa. T-cell subsets were measured using flow cytometry and plasma biomarkers using immunoassays.Results: HIV/HCV-coinfected patients had higher biomarker levels of immune activation in peripheral blood [T-cell activation (CD4(+)CD38(+) and CD8(+)CD38(+)), bacterial translocation (soluble CD14), inflammation [IL-1b, IL-6, IL-8, IL-18, IFN-gamma-inducible protein 10 (IP-10)] endothelial dysfunction [soluble vascular cell adhesion molecule 1 (sVCAM1), soluble intercellular cell adhesion molecule 1 (sICAM1), and soluble tumor necrosis factor receptor 1 (sTNFR1)], and coagulopathy (plasminogen activator inhibitor-1)] than healthy controls and HIV-monoinfected patients. Moreover, in HIV/HCVcoinfected patients, a direct relationship between LSM and immune activation [T-cell activation (CD8(+)CD38(+) bacterial translocation (lipopolysaccharide), inflammation (IL8, IP-10), endothelial dysfunction (sVCAM1, sICAM1, and sTNFR1), and coagulopathy (D-dimer)] was found. Subsequently, patients were stratified into different fibrosis stages, finding that patients with cirrhosis who had LSM at least 40 kPa showed higher biomarker values of immune activation [T-cell activation (CD4(+)CD38(+) and CD8(+)CD38(+)), bacterial translocation (lipopolysaccharide), inflammation (IL-8, IL-6, IP-10), endothelial dysfunction (sVCAM1, sICAM1, and sTNFR1), and coagulopathy (Ddimer)] than patients from the other three groups (< 12.5, 12.5-25, and 25-40 kPa).Conclusion: T-cell activation, bacterial translocation, inflammation, endothelial dysfunction, and coagulopathy increased with the severity of liver fibrosis in HIV/HCV- coinfected patients, particularly in patients who had LSM at least 40 kPa. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.