Novartis Institutes of Biomedical Research, Basel, Switzerland.
Novartis Institutes for Biomedical Research, East Hannover, New Jersey, USA.
Liver Int. 2023 Sep;43(9):1984-1994. doi: 10.1111/liv.15657. Epub 2023 Jul 13.
A reduction in hepatic venous pressure gradient (HVPG) is the most accurate marker for assessing the severity of portal hypertension and the effectiveness of intervention treatments. This study aimed to evaluate the prognostic potential of blood-based proteomic biomarkers in predicting HVPG response amongst cirrhotic patients with portal hypertension due to Hepatitis C virus (HCV) and had achieved sustained virologic response (SVR).
The study comprised 59 patients from two cohorts. Patients underwent paired HVPG (pretreatment and after SVR), liver stiffness (LSM), and enhanced liver fibrosis scores (ELF) measurements, as well as proteomics-based profiling on serum samples using SomaScan® at baseline (BL) and after SVR (EOS). Machine learning with feature selection (Caret, Random Forest and RPART) methods were performed to determine the proteins capable of classifying HVPG responders. Model performance was evaluated using AUROC (pROC R package).
Patients were stratified by a change in HVPG (EOS vs. BL) into responders (greater than 20% decline in HVPG from BL, or <10 mmHg at EOS with >10 mmHg at BL) and non-responders. LSM and ELF decreased markedly after SVR but did not correlate with HVPG response. SomaScan (SomaLogic, Inc., Boulder, CO) analysis revealed a substantial shift in the peripheral proteome composition, reflected by 82 significantly differentially abundant proteins. Twelve proteins accurately distinguished responders from non-responders, with an AUROC of .86, sensitivity of 83%, specificity of 83%, accuracy of 83%, PPV of 83%, and NPV of 83%.
A combined non-invasive soluble protein signature was identified, capable of accurately predicting HVPG response in HCV liver cirrhosis patients after achieving SVR.
肝静脉压力梯度（HVPG）的降低是评估门静脉高压严重程度和干预治疗效果的最准确标志物。本研究旨在评估基于血液的蛋白质组生物标志物在预测 HCV 相关肝硬化门静脉高压患者 SVR 后 HVPG 反应中的预后潜力。
该研究纳入了来自两个队列的 59 名患者。患者在 SVR 前后分别进行了 HVPG（基线和 SVR 后）、肝硬度（LSM）和增强肝纤维化评分（ELF）的配对测量，以及在基线（BL）和 SVR 后（EOS）使用 SomaScan®进行基于血清样本的蛋白质组学分析。使用 Caret、Random Forest 和 RPART 等机器学习特征选择方法，确定能够对 HVPG 反应者进行分类的蛋白质。使用 AUROC（pROC R 包）评估模型性能。
根据 HVPG（EOS 与 BL）的变化，将患者分为反应者（HVPG 从 BL 下降超过 20%，或 EOS 时 HVPG <10mmHg，BL 时 HVPG >10mmHg）和非反应者。SVR 后 LSM 和 ELF 明显降低，但与 HVPG 反应无关。SomaScan（SomaLogic，Inc.，博尔德，CO）分析显示外周蛋白质组组成发生了实质性变化，反映在 82 种显著差异丰度的蛋白质上。12 种蛋白质可准确区分反应者和非反应者，AUROC 为 0.86，敏感性为 83%，特异性为 83%，准确性为 83%，PPV 为 83%，NPV 为 83%。
确定了一种联合的非侵入性可溶性蛋白质特征，能够准确预测 HCV 肝硬化患者 SVR 后 HVPG 反应。
