Gastroenterology Research Unit, Department of Physiology, Advanced Liver Disease Study Group, Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Liver Int. 2010 Feb;30(2):191-7. doi: 10.1111/j.1478-3231.2009.02132.x. Epub 2009 Oct 19.
BACKGROUND/AIMS: Peripheral circulating endothelial cells (CEC) have been proposed as a prognostic marker in cardiovascular diseases. Cirrhosis and portal hypertension are associated with vascular injury yet little is known about CEC count in these conditions. Therefore, we evaluated CEC count in patients with cirrhosis, and correlated it with markers of portal hypertension/disease severity.
PATIENTS/METHODS: Fifteen patients with cirrhosis/portal hypertension and 15 matched controls were prospectively recruited for study participation. An automated rare cell analysis system was used to enumerate CEC from peripheral blood and correlated with clinical features.
Median CEC levels were significantly higher in patients with cirrhosis as compared with controls (median [interquartile range (IQR)]; cirrhosis: 73.7 cells/4 ml [53.7-140.3]; controls: 28.7 cells/4 ml [21-58.7]; P=0.021). Ratio of CEC to platelet count (CEC/PC) also distinguished patients with cirrhosis from controls (IQR; cirrhosis: 0.723 [0.396-1.672]; controls: 0.126 [0.103-0.333]; P<0.001). Receiver operator characteristic analysis revealed that CEC cut-off of 42 cells/4 ml showed sensitivity of 87% and specificity of 74% for differentiating cirrhosis from controls (AUC: 0.74), while CEC/PC ratio at 0.21 showed sensitivity of 100% and specificity of 73% (AUC: 0.89). Furthermore, CEC/PC index was significantly elevated in patients with hepatic decompensation as defined by Child B/C (P<0.05). The intra- and interobserver variability correlation coefficients for CEC measurement were 0.9989 and 0.9986 respectively.
Median CEC count and CEC/PC ratio are significantly elevated in patients with cirrhosis, with CEC/PC also increased in patients with decompensated cirrhosis. These data provide rationale for larger validation studies to assess if CEC may have prognostic utility in patients with cirrhosis and portal hypertension.
背景/目的:外周循环内皮细胞(CEC)已被提议作为心血管疾病的预后标志物。肝硬化和门静脉高压与血管损伤有关,但对于这些疾病中 CEC 计数知之甚少。因此,我们评估了肝硬化患者的 CEC 计数,并将其与门静脉高压/疾病严重程度的标志物相关联。
患者/方法:前瞻性招募了 15 名肝硬化/门静脉高压患者和 15 名匹配的对照者参与研究。使用自动化稀有细胞分析系统从外周血中计数 CEC,并与临床特征相关联。
与对照组相比,肝硬化患者的 CEC 水平中位数显著升高(中位数[四分位距(IQR)];肝硬化:73.7 个/4 毫升[53.7-140.3];对照组:28.7 个/4 毫升[21-58.7];P=0.021)。CEC 与血小板计数的比值(CEC/PC)也能区分肝硬化患者和对照组(IQR;肝硬化:0.723[0.396-1.672];对照组:0.126[0.103-0.333];P<0.001)。受试者工作特征分析显示,CEC 截断值为 42 个/4 毫升时,区分肝硬化和对照组的敏感性为 87%,特异性为 74%(AUC:0.74),而 CEC/PC 比值为 0.21 时,敏感性为 100%,特异性为 73%(AUC:0.89)。此外,CEC/PC 指数在定义为 Child B/C 的肝功能失代偿患者中显著升高(P<0.05)。CEC 测量的观察者内和观察者间变异性相关系数分别为 0.9989 和 0.9986。
肝硬化患者的 CEC 计数和 CEC/PC 比值中位数显著升高,失代偿性肝硬化患者的 CEC/PC 比值也升高。这些数据为更大规模的验证研究提供了依据,以评估 CEC 是否在肝硬化和门静脉高压患者中具有预后效用。