Kaur Savneet, Hussain Sadam, Kolhe Kailash, Kumar Guresh, Tripathi Dinesh M, Tomar Arvind, Kale Pratibha, Narayanan Ashad, Bihari Chaggan, Bajpai Meenu, Maiwall Rakhi, Gupta Ekta, Sarin Shiv K
Department of Molecular and Cellular Medicine, Institute of liver and biliary Sciences, New Delhi, India.
Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, India.
JHEP Rep. 2021 Aug;3(4):100303. doi: 10.1016/j.jhepr.2021.100303. Epub 2021 May 8.
BACKGROUND & AIMS: Endothelial injury and dysfunction play a detrimental role in the pathogenesis of infections. Endothelium-related molecules have been reported as potential diagnostic and/or prognostic biomarkers of infection. The prognostic value of these biomarkers in patients with cirrhosis and infections remains elusive.
In this study, we investigated the performance of key soluble endothelial injury biomarkers, including intercellular adhesion molecule 1 (ICAM1), von Willebrand factor (vWF), vascular endothelial growth factor receptor 1 (VEGFR1), and angiopoietin 1 and 2 (Ang1, 2) as mortality predictors in patients with cirrhosis and severe COVID-19 or bacterial sepsis.
A total of 66 hospitalized patients (admitted to the COVID-19 ward or liver intensive care unit [ICU]) were included. Twenty-two patients had COVID-19 alone, while 20 patients had cirrhosis plus COVID-19. Twenty-four patients had cirrhosis plus bacterial sepsis. Among patients with cirrhosis, the most common aetiology of liver disease was alcohol. ICAM1 was increased ( 0.003) while VEGFR1 (0.0001) and Ang1 (0.0001) were reduced in patients with COVID-19 and cirrhosis, compared to patients with COVID-19 alone. Endothelial biomarker levels did not differ significantly between patients with cirrhosis and severe COVID-19 or bacterial sepsis in the ICU. In these patients, ICAM1 levels significantly and independently predicted mortality (hazard ratio 3.24; 95% CI 1.19-8.86) along with model for end-stage liver disease (MELD) score, renal and coagulation failures. The AUC for ICAM1 was 0.74, MELD was 0.60 and combined ICAM1 and MELD was 0.70. ICAM1 also positively correlated with the composite organ failure scores recorded 3-5 days post ICU admission (CLIF-OF and SOFA) in this subgroup of patients.
The study indicates that in patients with cirrhosis, elevated plasma ICAM1 serves as an independent predictor of severe COVID-19- or sepsis-associated 28-day mortality.
Bacterial sepsis and COVID-19 lead to increased mortality in patients with cirrhosis. In this study, we demonstrate that high plasma levels of ICAM1, an endothelial injury biomarker, is one of the important factors predicting mortality in critically ill cirrhotic patients with severe COVID-19 or bacterial sepsis.
内皮损伤和功能障碍在感染的发病机制中起有害作用。内皮相关分子已被报道为感染的潜在诊断和/或预后生物标志物。这些生物标志物在肝硬化合并感染患者中的预后价值仍不明确。
在本研究中，我们调查了关键可溶性内皮损伤生物标志物的表现，包括细胞间黏附分子1（ICAM1）、血管性血友病因子（vWF）、血管内皮生长因子受体1（VEGFR1）以及血管生成素1和2（Ang1、Ang2）作为肝硬化合并重症COVID-19或细菌性脓毒症患者死亡率预测指标的情况。
共纳入66例住院患者（收治于COVID-19病房或肝脏重症监护病房[ICU]）。22例患者仅患有COVID-19，20例患者患有肝硬化合并COVID-19。24例患者患有肝硬化合并细菌性脓毒症。在肝硬化患者中，最常见的肝病病因是酒精。与仅患有COVID-19的患者相比，患有COVID-19和肝硬化的患者ICAM1升高（P<0.003），而VEGFR1（P<0.0001）和Ang1（P<0.0001）降低。肝硬化合并重症COVID-19或ICU中的细菌性脓毒症患者之间的内皮生物标志物水平无显著差异。在这些患者中，ICAM1水平与终末期肝病模型（MELD）评分、肾脏和凝血功能衰竭一起显著且独立地预测死亡率（风险比3.24；95%置信区间1.19 - 8.86）。ICAM1的曲线下面积为0.74，MELD为0.60，ICAM1与MELD联合为0.70。在该亚组患者中，ICAM1还与ICU入院后3 - 5天记录的综合器官衰竭评分（CLIF - OF和SOFA）呈正相关。
该研究表明，在肝硬化患者中，血浆ICAM1升高是重症COVID-19或脓毒症相关28天死亡率的独立预测指标。
细菌性脓毒症和COVID-19导致肝硬化患者死亡率增加。在本研究中，我们证明血浆中高水平的ICAM1（一种内皮损伤生物标志物）是预测重症COVID-19或细菌性脓毒症的重症肝硬化患者死亡率的重要因素之一。
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