Endothelial dysfunction markers predict short-term mortality in patients with severe alcoholic hepatitis,Hepatology International

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Endothelial dysfunction markers predict short-term mortality in patients with severe alcoholic hepatitis
Hepatology International ( IF 6.6 ) Pub Date : 2021-05-05 , DOI: 10.1007/s12072-021-10165-y
Delia Blaya ₁ , Teresa Rubio-Tomás _{1,

2} , Daniel Rodrigo-Torres ₁ , JuanJosé Lozano _{1,

3} , Mar Coll _{1,

3} , Josepmaria Argemi _{4,

5} , José Altamirano ₁ , Silvia Affò ₁ , Oriol Morales-Ibanez ₁ , Jordi Gratacós-Ginès ₃ , Elisa Pose _{1,

3,

6} , Marion Tanguy _{7,

8} , Tazime Issoufaly _{7,

8} , Pierre-Emmanuel Rautou _{7,

8} , Ramon Bataller ₄ , Joan Caballería _{1,

6} , Pau Sancho-Bru _{1,

3,

9}

Affiliation

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/ Rosselló, 149-153, 08036, Barcelona, Spain.
School of Medicine, University of Crete, 70013, Heraklion, Crete, Greece.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Center for Liver Diseases, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
Liver Unit, Clínica Universidad de Navarra, Hepatology Program, Centro de Investigación Medica Aplicada, IdisNA, Universidad de Navarra, Pamplona, Spain.
Liver Unit, Hospital Clínic, Barcelona, Spain.
Service d'Hépatologie, DHU Unity, Pôle des Maladies de l'Appareil Digestif, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Paris, France.
Centre de Référence des Maladies Vasculaires du Foie, French Network for Rare Liver Diseases, European Reference Network Rare-Liver, Centre de Recherche sur l'inflammation, Inserm, Université de Paris, Paris, France.
Universitat de Barcelona, Barcelona, Spain.

Objectives

Alcoholic hepatitis (AH) is a severe condition characterized by a marked inflammatory response and high short-term mortality. Endothelial dysfunction (ED) is an early event in vascular and inflammatory disorders. The aim of this study is to evaluate ED in AH patients.

Methods

Prognostic value of ED biomarkers was evaluated in patients with severe AH (n = 67), compensated alcoholic cirrhosis (n = 15), heavy drinkers without liver disease (n = 15) and controls (n = 9), and in a validation cohort of 50 patients with AH. Gene expression of ED markers was analyzed in liver tissue.

Results

Plasma levels of ED markers such as vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin and von Willebrand factor (vWF) increased along alcohol-related liver disease (ALD) progression. Intergroup analysis showed a significant increase of these markers in AH patients. In addition, VCAM-1 showed a positive correlation with Maddrey, MELD and ABIC scores and inflammation parameters (i.e. C-reactive protein and LPS levels). Importantly, levels of VCAM-1 were higher in patients with increased mortality and were independently associated with short-term survival (90-day) when adjusted by ABIC score. These results were confirmed in an independent cohort of AH patients. In addition, severe AH patients showed altered hepatic expression of ED markers.

Conclusions

In this study we show that advanced ALD and particularly severe AH is associated with an increase of ED biomarkers, which correlate with patient outcomes. These results suggest that ED may be a pathogenic event in AH and highlight endothelial factors as potential biomarkers in AH.

中文翻译：

内皮功能障碍标志物预测重度酒精性肝炎患者的短期死亡率

目标

酒精性肝炎 (AH) 是一种以显着的炎症反应和高短期死亡率为特征的严重疾病。内皮功能障碍 (ED) 是血管和炎症性疾病的早期事件。本研究的目的是评估 AH 患者的 ED。

方法

ED 生物标志物的预后价值在重度 AH 患者（n = 67）、代偿期酒精性肝硬化（n = 15）、无肝病重度饮酒者（n = 15）和对照组（n = 9）以及验证队列中进行了评估50 名 AH 患者。在肝组织中分析了 ED 标记的基因表达。

结果

血管细胞粘附分子 1 (VCAM-1)、细胞间粘附分子 1 (ICAM-1)、E-选择素和血管性血友病因子 (vWF) 等 ED 标志物的血浆水平随着酒精相关肝病 (ALD) 的进展而增加。组间分析显示 AH 患者的这些标志物显着增加。此外，VCAM-1 与 Maddrey、MELD 和 ABIC 评分以及炎症参数（即 C 反应蛋白和 LPS 水平）呈正相关。重要的是，VCAM-1 水平在死亡率增加的患者中更高，并且在通过 ABIC 评分调整后与短期生存（90 天）独立相关。这些结果在 AH 患者的独立队列中得到证实。此外，严重的 AH 患者表现出 ED 标志物的肝脏表达改变。