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血小板内皮细胞黏附分子-1 和可溶性血管细胞黏附分子-1:在慢性丙型肝炎发病机制和诊断中的作用及其与抗病毒治疗反应的关系。

sPECAM-1 and sVCAM-1: Role in Pathogenesis and Diagnosis of Chronic Hepatitis C and Association with Response to Antiviral Therapy.

机构信息

Department of Physiology, Medical University of Silesia, Zabrze, Poland.

出版信息

Therap Adv Gastroenterol. 2009 Mar;2(2):79-90. doi: 10.1177/1756283X08100666.

Abstract

AIM

To analyze the relationship between pretreatment clinical or histological features and the levels of soluble platelet-endothelial cell adhesion molecule-1 (sPECAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), to determine their serum concentration in responders and nonresponders, to evaluate the behavior under antiviral therapy, to explain their relationship in response to therapy and to assess the association between these two molecules in chronic hepatitis C (CHC).

METHODS

The study analyzed 65 CHC patients, including 50 patients (Group 1) with marked fibrosis treated with peginterferon plus ribavirin, 15 patients without fibrosis (Group 2) and 13 healthy volunteers (the control group, Group 3). sPECAM-1 and sVCAM-1 levels were assessed by an immunoenzymatic method (ELISA) before and after therapy.

RESULTS

sVCAM-1 and sPECAM-1 serum concentrations increased significantly in CHC patients (p<001). sPECAM-1 levels corresponded to inflammatory grade (p = 0.03) and fibrosis stage (p =0.01). sVCAM-1 increased only in advanced fibrosis. After therapy, sPECAM-1 levels decreased significantly (p<001) with no difference between responders and nonre-sponders. sPECAM-1 correlated positively with inflammatory activity (p = 0.02), fibrosis stage (p<001), sVCAM-1 (r=0.56, p<001) and alanine aminotransferase activity (r = 0.30, p = 0.05). Receiver operating characteristic curve analysis showed a good discriminant power of serum sPECAM-1 concentrations for detection of liver fibrosis - stage 0 versus stage 1-3, AUC 0.81; cut-off 221.0 ng/ml and a fair discriminant power for distinguishing bridging fibrosis, AUC 0.78; cut-off 237.1 ng/ml.

CONCLUSIONS

Hepatitis C virus (HCV) infection results in upregulation of sPECAM-1 and sVCAM-1. sPECAM-1 levels are related to necroinflammatory activity and may also identify patients with advanced fibrosis. The sPECAM-1 value was decreased by therapy but its measurement cannot predict therapy outcome and confirm HCV persistence. sPECAM-1 may influence VCAM-1 expression.

摘要

目的

分析预处理临床或组织学特征与可溶性血小板内皮细胞黏附分子-1(sPECAM-1)和可溶性血管细胞黏附分子-1(sVCAM-1)水平之间的关系,确定它们在应答者和无应答者中的血清浓度,评估抗病毒治疗下的行为,解释其治疗应答中的关系,并评估慢性丙型肝炎(CHC)中这两种分子之间的相关性。

方法

本研究分析了 65 例 CHC 患者,包括 50 例(第 1 组)有明显纤维化的患者,接受聚乙二醇干扰素加利巴韦林治疗,15 例无纤维化的患者(第 2 组)和 13 例健康志愿者(对照组,第 3 组)。采用酶联免疫吸附法(ELISA)检测治疗前后 sPECAM-1 和 sVCAM-1 水平。

结果

CHC 患者 sVCAM-1 和 sPECAM-1 血清浓度显著升高(p<001)。sPECAM-1 水平与炎症等级(p = 0.03)和纤维化阶段(p =0.01)相对应。sVCAM-1 仅在晚期纤维化中增加。治疗后,sPECAM-1 水平显著降低(p<001),应答者和无应答者之间无差异。sPECAM-1 与炎症活动(p = 0.02)、纤维化阶段(p<001)、sVCAM-1(r=0.56,p<001)和丙氨酸氨基转移酶活性(r = 0.30,p = 0.05)呈正相关。受试者工作特征曲线分析显示,血清 sPECAM-1 浓度对检测肝纤维化-0 期与 1-3 期有很好的判别能力,AUC 0.81;截断值 221.0 ng/ml,对桥接纤维化的判别能力尚可,AUC 0.78;截断值 237.1 ng/ml。

结论

丙型肝炎病毒(HCV)感染导致 sPECAM-1 和 sVCAM-1 的上调。sPECAM-1 水平与坏死性炎症活动有关,也可能识别出晚期纤维化的患者。治疗后 sPECAM-1 水平降低,但检测不能预测治疗效果和证实 HCV 持续存在。sPECAM-1 可能影响 VCAM-1 的表达。

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