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前C5是真正的V型胶原形成和原纤维形成的标志物,与酒精性肝硬化患者的门静脉高压相关。

Pro-C5, a marker of true type V collagen formation and fibrillation, correlates with portal hypertension in patients with alcoholic cirrhosis.

作者信息

Leeming Diana J, Veidal Sanne S, Karsdal Morten A, Nielsen Mette Juul, Trebicka Jonel, Busk Troels, Bendtsen Flemming, Krag Aleksander, Møller Søren

机构信息

Nordic Bioscience, Fibrosis Biology and Biomarkers , Herlev , Denmark.

出版信息

Scand J Gastroenterol. 2015 May;50(5):584-92. doi: 10.3109/00365521.2014.996590. Epub 2015 Feb 1.

Abstract

BACKGROUND AND AIMS

The hepatic venous pressure gradient (HVPG) is an important but invasive diagnostic and prognostic marker in cirrhotic patients. The aim of the study was to evaluate a novel biochemical plasma marker of true type V collagen formation (Pro-C5) for describing HVPG.

METHODS

Ninety-four patients mainly with alcoholic cirrhosis and fourteen liver-healthy controls were included in a retrospective study. Relevant clinical and routine laboratory data and hemodynamics were determined. Plasma Pro-C5 was correlated to HVPG and liver function parameters. Furthermore, Pro-C5 was combined in a linear regression model.

RESULTS

Plasma Pro-C5 correlated to HVPG, indocyanine green clearance, sustained vascular resistance and mean arterial pressure (r = -0.68-0.33, p < 0.0001). A multiple regression analysis including Pro-C5, alanine aminotransferase, bilirubin and model for end-stage liver disease (MELD) improved the correlation to HVPG (r = 0.74, p < 0.0001). Plasma Pro-C5 was positively or negatively correlated to a number of routine liver function markers and MELD score (r = 0.27-0.68; p < 0.05-0.0001). Furthermore, plasma Pro-C5 could clearly separate patients with a HVPG <10 mmHg or HVPG ≥10 mmHg (p < 0.001, area under the curve (AUC) = 0.73), HVPG 10-<16 mmHg or HVPG ≥16 mmHg (p < 0.001, AUC = 0.68) and controls from diseased patients (p < 0.0001, AUC = 0.88). Finally, there was a clear relation to increasing Child score A-C and plasma Pro-C5 (ANOVA p < 0.001).

CONCLUSION

Plasma Pro-C5 reflects liver hemodynamics, liver function, disease stage and clinically significant portal hypertension (PH). A multimarker model in combination with clinical scores predicted HVPG and separated clinical relevant HVPG thresholds. Plasma Pro-C5 may be suitable for the noninvasive evaluation of PH in patients with cirrhosis.

摘要

背景与目的

肝静脉压力梯度(HVPG)是肝硬化患者重要的诊断和预后指标,但具有侵入性。本研究旨在评估一种用于描述HVPG的新型血浆生化标志物——真实Ⅴ型胶原形成标志物(Pro-C5)。

方法

94例主要为酒精性肝硬化患者和14例肝脏健康对照者纳入一项回顾性研究。测定相关临床、常规实验室数据及血流动力学指标。分析血浆Pro-C5与HVPG及肝功能参数的相关性。此外,将Pro-C5纳入线性回归模型。

结果

血浆Pro-C5与HVPG、吲哚菁绿清除率、持续血管阻力及平均动脉压相关(r = -0.68 - 0.33,p < 0.0001)。包含Pro-C5、丙氨酸氨基转移酶、胆红素及终末期肝病模型(MELD)的多元回归分析改善了与HVPG的相关性(r = 0.74,p < 0.0001)。血浆Pro-C5与多项常规肝功能指标及MELD评分呈正相关或负相关(r = 0.27 - 0.68;p < 0.05 - 0.0001)。此外,血浆Pro-C5能清晰区分HVPG <10 mmHg或HVPG≥10 mmHg的患者(p < 0.001,曲线下面积(AUC) = 0.73)、HVPG 10 - <16 mmHg或HVPG≥16 mmHg的患者(p < 0.001,AUC = 0.68)以及健康对照与患病患者(p < 0.0001,AUC = 0.88)。最后,Child评分A - C升高与血浆Pro-C5存在明显关联(方差分析p < 0.001)。

结论

血浆Pro-C5反映肝脏血流动力学、肝功能、疾病分期及具有临床意义的门静脉高压(PH)。多标志物模型联合临床评分可预测HVPG并区分临床相关的HVPG阈值。血浆Pro-C5可能适用于肝硬化患者PH的无创评估。

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