DuBrock Hilary M, Rodriguez-Lopez Josanna M, LeVarge Barbara L, Curry Michael P, VanderLaan Paul A, Zsengeller Zsuzsanna K, Pernicone Elizabeth, Preston Ioana R, Yu Paul B, Nikolic Ivana, Xu Dihua, Thadhani Ravi I, Channick Richard N, Ananth Karumanchi S
Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Massachusetts General Hospital, Boston, Massachusetts, USA.
Pulm Circ. 2016 Dec;6(4):498-507. doi: 10.1086/688489.
Portopulmonary hypertension (POPH) is a poorly understood complication of liver disease associated with significant morbidity and mortality. We sought to identify novel biomarkers of POPH disease presence and severity. We performed a prospective, multicenter, case-control study involving patients with liver disease undergoing right heart catheterization. POPH cases were defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg and pulmonary vascular resistance (PVR) >240 dynes˙s˙cm. Plasma samples were collected from the systemic and pulmonary circulation, and antibody microarray was used to identify biomarkers. Characterization and validation of a candidate cytokine, macrophage migration inhibitory factor (MIF), was performed using enzyme-linked immunosorbent assay. Continuous variables were compared using a Mann-Whitney test and correlated with disease severity using Spearman correlation. MIF levels were elevated in both the systemic and pulmonary circulation in patients with POPH compared with controls (median MIF level [interquartile range] in systemic circulation: 46.68 ng/mL [32.31-76.04] vs. 31.19 ng/mL [26.92-42.17], = 0.009; in pulmonary circulation: 49.59 ng/mL [35.90-108.80] vs. 37.78 [21.78-45.53], = 0.002). In patients with POPH, MIF levels were positively correlated with PVR ( = 0.58, = 0.006) and inversely correlated with cardiac output ( = -0.57, = 0.007). MIF >60 ng/mL or tricuspid regurgitation gradient >50 mmHg had a 92% sensitivity and specificity for the diagnosis of POPH, with a positive predictive value of 86% and a negative predictive value of 96%. MIF is a promising novel biomarker of POPH disease presence and severity in patients with liver disease and portal hypertension.
门肺高压（POPH）是一种人们了解较少的肝脏疾病并发症，与显著的发病率和死亡率相关。我们试图确定POPH疾病存在和严重程度的新型生物标志物。我们进行了一项前瞻性、多中心、病例对照研究，纳入了接受右心导管检查的肝病患者。POPH病例定义为平均肺动脉压（mPAP）≥25 mmHg且肺血管阻力（PVR）>240达因·秒·厘米。从体循环和肺循环采集血浆样本，并使用抗体微阵列来识别生物标志物。使用酶联免疫吸附测定法对候选细胞因子巨噬细胞迁移抑制因子（MIF）进行表征和验证。连续变量采用曼-惠特尼检验进行比较，并使用斯皮尔曼相关性分析与疾病严重程度进行关联。与对照组相比，POPH患者的体循环和肺循环中MIF水平均升高（体循环中MIF水平的中位数[四分位间距]：46.68 ng/mL[32.31 - 76.04] vs. 31.19 ng/mL[26.92 - 42.17]，P = 0.009；肺循环中：49.59 ng/mL[35.90 - 108.80] vs. 37.78[21.78 - 45.53]，P = 0.002）。在POPH患者中，MIF水平与PVR呈正相关（r = 0.58，P = 0.006），与心输出量呈负相关（r = -0.57，P = 0.007）。MIF>60 ng/mL或三尖瓣反流梯度>50 mmHg对POPH诊断的敏感性为92%，特异性为92%，阳性预测值为86%，阴性预测值为96%。MIF是肝病和门静脉高压患者中POPH疾病存在和严重程度的一种有前景的新型生物标志物。
