Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.
AIDS. 2018 Jun 1;32(9):1095-1105. doi: 10.1097/QAD.0000000000001787.
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.
Cross-sectional study.
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.
HIV/HCV-coinfected patients had higher biomarker levels of immune activation in peripheral blood [T-cell activation (CD4CD38 and CD8CD38), bacterial translocation (soluble CD14), inflammation [IL-1b, IL-6, IL-8, IL-18, IFN-γ-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/HCV-coinfected patients, a direct relationship between LSM and immune activation [T-cell activation (CD8CD38 bacterial translocation (lipopolysaccharide), inflammation (IL-8, 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 (CD4CD38 and CD8CD38), bacterial translocation (lipopolysaccharide), inflammation (IL-8, IL-6, IP-10), endothelial dysfunction (sVCAM1, sICAM1, and sTNFR1), and coagulopathy (D-dimer)] than patients from the other three groups (<12.5, 12.5-25, and 25-40 kPa).
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.
免疫失调是 HIV 和丙型肝炎病毒（HCV）感染的标志。我们旨在评估 HIV/HCV 合并感染患者的肝硬度测量（LSM）与 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。
横断面研究。
我们研究了 238 例 HIV/HCV 合并感染患者、32 名健康对照者和 39 例 HIV 单感染患者。根据 LSM 将患者分为四组：<12.5kPa、12.5-25kPa、25-40kPa 和>40kPa。使用流式细胞术测量 T 细胞亚群，使用免疫测定法测量血浆生物标志物。
HIV/HCV 合并感染患者外周血中免疫激活的生物标志物水平较高[T 细胞活化（CD4CD38 和 CD8CD38）、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[可溶性血管细胞黏附分子 1（sVCAM1）、可溶性细胞间黏附分子 1（sICAM1）和可溶性肿瘤坏死因子受体 1（sTNFR1）]和凝血功能障碍（纤溶酶原激活物抑制剂-1）]高于健康对照者和 HIV 单感染患者。此外，在 HIV/HCV 合并感染患者中，LSM 与免疫激活[T 细胞活化（CD8CD38）、细菌易位（脂多糖）、炎症（IL-8、IP-10）]、内皮功能障碍（sVCAM1、sICAM1 和 sTNFR1）和凝血功能障碍（D-二聚体）]呈直接关系。随后，根据不同的纤维化阶段对患者进行分层，发现 LSM 至少为 40kPa 的肝硬化患者具有更高的免疫激活生物标志物值[T 细胞活化（CD4CD38 和 CD8CD38）、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（D-二聚体）]高于其他三组患者（<12.5kPa、12.5-25kPa 和 25-40kPa）。
T 细胞活化、细菌易位、炎症、内皮功能障碍和凝血功能障碍在 HIV/HCV 合并感染患者中随肝纤维化严重程度的增加而增加，尤其是在 LSM 至少为 40kPa 的患者中。
