Leeming Diana J, Veidal Sanne S, Karsdal Morten A, Nielsen Mette Juul, Trebicka Jonel, Busk Troels, Bendtsen Flemming, Krag Aleksander, Møller Søren
Nordic Bioscience, Fibrosis Biology and Biomarkers , Herlev , Denmark.
Scand J Gastroenterol. 2015 May;50(5):584-92. doi: 10.3109/00365521.2014.996590. Epub 2015 Feb 1.
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.
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.
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).
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.
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）。
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。
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）。
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。
