血浆 Nogo-A 和胎盘生长因子水平与肝硬化患者的门静脉高压相关。
Plasma Nogo-A and placental growth factor levels are associated with portal hypertension in patients with liver cirrhosis.
机构信息
Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania.
Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania.
出版信息
World J Gastroenterol. 2019 Jun 21;25(23):2935-2946. doi: 10.3748/wjg.v25.i23.2935.
BACKGROUND
Clinically significant portal hypertension (CSPH) and severe portal hypertension (SPH) increase the risk for decompensation and life-threatening complications in liver cirrhosis. Pathologic angiogenesis might contribute to the formation of these conditions. Placental growth factor (PlGF) and Nogo-A protein are biomarkers of pathological angiogenesis, but data on their role in liver cirrhosis and portal hypertension is scarce.
AIM
To determine plasma levels of PlGF and Nogo-A in patients with liver cirrhosis, CSPH, SPH and potential to predict portal hypertension.
METHODS
A cohort of 122 patients with hepatitis C virus and/or alcohol-induced liver cirrhosis with characterized hepatic venous pressure gradient (HVPG) were included in the study. Demographic data, medical history, Child-Turcotte-Pugh and Model of End Stage liver disease score, clinical chemistry, liver stiffness values were recorded on the day of the procedure prior HVPG measurement. The degree of portal hypertension was determined by the invasive HVPG measurement. Nogo-A and PlGF plasma levels were evaluated using enzyme linked immunosorbent assay. The control group consisted of 30 healthy age- and sex- matched individuals.
RESULTS
Peripheral PlGF levels were higher and Nogo-A levels were lower in patients with liver cirrhosis (23.20 9.85; < 0.0001 and 2.19 3.12; = 0.004 respectively). There was a positive linear correlation between peripheral levels of PlGF and HVPG ( = 0.338, = 0.001) and negative linear correlation between the peripheral Nogo-A levels and HVPG ( = -0.267, = 0.007). PlGF levels were higher in CSPH and SPH ( = 0.006; < 0.0001) whereas Nogo-A levels were lower ( = 0.01; < 0.033). Area under the curve for the diagnosis of CSPH for PlGF was 0.68 ( = 0.003) and for Nogo-A - 0.67 ( = 0.01); for SPH 0.714 ( < 0.0001) and 0.65 ( = 0.014) respectively. PlGF levels were higher and Nogo-A levels were lower in patients with esophageal varices ( < 0.05). PlGF cut-off value of 25 pg/mL distinguished patients with CSPH at 55.7% sensitivity and 76.7% specificity; whereas Nogo-A cut-off value of 1.12 ng/mL was highly specific (93.1%) for the diagnosis of CSPH.
CONCLUSION
Plasma PlGF levels were higher while Nogo-A levels were lower in patients with liver cirrhosis and portal hypertension. Biomarkers showed moderate predictive value in determining CSPH and SPH.
背景
临床上显著的门静脉高压症（CSPH）和严重的门静脉高压症（SPH）会增加肝硬化失代偿和危及生命并发症的风险。病理性血管生成可能导致这些情况的形成。胎盘生长因子（PlGF）和 Nogo-A 蛋白是病理性血管生成的生物标志物，但关于它们在肝硬化和门静脉高压症中的作用的数据却很少。
目的
确定肝硬化、CSPH 和 SPH 患者的血浆 PlGF 和 Nogo-A 水平，并确定其预测门静脉高压症的潜力。
方法
本研究纳入了 122 名患有丙型肝炎病毒和/或酒精性肝肝硬化的患者，这些患者的肝静脉压力梯度（HVPG）特征明确。在进行 HVPG 测量之前的当天记录人口统计学数据、病史、Child-Turcotte-Pugh 和终末期肝病模型评分、临床化学、肝硬度值。门静脉高压症的严重程度通过有创性 HVPG 测量来确定。使用酶联免疫吸附试验评估 Nogo-A 和 PlGF 的血浆水平。对照组由 30 名年龄和性别匹配的健康个体组成。
结果
肝硬化患者外周血 PlGF 水平升高，Nogo-A 水平降低（23.20 9.85；<0.0001 和 2.19 3.12；=0.004）。外周血 PlGF 水平与 HVPG 呈正线性相关（=0.338，=0.001），外周血 Nogo-A 水平与 HVPG 呈负线性相关（= -0.267，=0.007）。CSPH 和 SPH 患者的 PlGF 水平较高（=0.006；<0.0001），而 Nogo-A 水平较低（=0.01；<0.033）。PlGF 诊断 CSPH 的曲线下面积为 0.68（=0.003），Nogo-A 为 0.67（=0.01）；SPH 为 0.714（<0.0001）和 0.65（=0.014）。食管静脉曲张患者的 PlGF 水平较高，Nogo-A 水平较低（<0.05）。PlGF 的截断值为 25 pg/mL 时，其对 CSPH 的敏感性为 55.7%，特异性为 76.7%；而 Nogo-A 的截断值为 1.12 ng/mL 时，对 CSPH 的诊断具有很高的特异性（93.1%）。
结论
肝硬化和门静脉高压症患者的血浆 PlGF 水平升高，而 Nogo-A 水平降低。生物标志物对确定 CSPH 和 SPH 具有中等的预测价值。
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