Liver Pathobiology Laboratory, Department of Internal Medicine, Carolinas Medical Center, Charlotte, NC, 28203, USA.
Center for Liver Diseases and Liver Transplant, Department of Internal Medicine, Carolinas Medical Center, Charlotte, NC, 28203, USA.
Dig Dis Sci. 2018 Mar;63(3):653-664. doi: 10.1007/s10620-017-4860-z. Epub 2018 Jan 12.
Hepatitis C virus (HCV)-related cirrhosis, one of the most common etiologies of liver cirrhosis in the Western world, is a risk factor for hepatocellular carcinoma. To confirm and improve current effectiveness of screening and prognosis of patients with established cirrhosis, a credible, simple plasma biomarker is needed. Hepatic stellate cell activation, a pivotal event in cirrhosis development, results in increased secretion of extracellular matrix proteins, including tenascin-C (TnC). Herein, we tested TnC as a simple biomarker to identify cirrhotic patients with active HCV infection from those with HCV eradication.
A prospective study of subjects with HCV-related cirrhosis, stratified into two groups, HCV or virologic cure, was conducted. Plasma TnC expression was measured by ELISA and Western blots. TnC values were correlated with markers of liver injury and ROC analyses performed between groups.
The HCV cirrhotic cohort, consisting mostly of men (56%), Caucasians (76%), and genotype 1a or 1b (84%), was compared to healthy controls (HCs). Plasma TnC was significantly higher in HCV cirrhotic patients with active infection compared to HCs (P < 0.0001) and virologic cure (P < 0.0001). TnC concentrations in virologic cure subjects were not statistically different from HCs. TnC levels correlated with AST, platelets, MELD, APRI, FIB-4, and Child-Pugh score. TnC and AST together were significantly better indicators of cirrhosis in patients with active HCV infection than other markers tested.
TnC and AST provided the best model for discriminating HCV cirrhotics with active infection from HC and virologic cure cohorts over current liver injury markers, suggesting TnC as a potential indicator of ongoing hepatic injury and inflammation.
丙型肝炎病毒（HCV）相关的肝硬化是西方世界最常见的肝硬化病因之一，也是肝细胞癌的危险因素。为了确认和改善已确诊肝硬化患者的筛查和预后的有效性，需要一种可靠、简单的血浆生物标志物。肝星状细胞的激活是肝硬化发展的关键事件，导致细胞外基质蛋白（包括 tenascin-C[TnC]）的分泌增加。在此，我们测试了 TnC 作为一种简单的生物标志物，以识别出具有活跃 HCV 感染的肝硬化患者与 HCV 清除的患者。
对 HCV 相关肝硬化患者进行前瞻性研究，分为 HCV 或病毒学治愈两组。通过 ELISA 和 Western blot 检测血浆 TnC 表达。将 TnC 值与肝损伤标志物相关联，并对两组间进行 ROC 分析。
HCV 肝硬化队列主要由男性（56%）、白种人（76%）和基因型 1a 或 1b（84%）组成，与健康对照组（HCs）相比。与 HCs（P<0.0001）和病毒学治愈（P<0.0001）相比，活跃感染的 HCV 肝硬化患者的血浆 TnC 显著升高。病毒学治愈患者的 TnC 浓度与 HCs 相比无统计学差异。TnC 水平与 AST、血小板、MELD、APRI、FIB-4 和 Child-Pugh 评分相关。与其他测试标志物相比，TnC 和 AST 联合是区分活跃 HCV 感染的肝硬化患者与 HCs 和病毒学治愈患者的最佳指标。
TnC 和 AST 比当前的肝损伤标志物更能区分活跃 HCV 感染的肝硬化患者与 HCs 和病毒学治愈患者，提示 TnC 可能是持续肝损伤和炎症的潜在指标。
