Leukocytes, Systemic Inflammation and Immunopathology in Acute-on-Chronic Liver Failure.
Leukocytes, Systemic Inflammation and Immunopathology in Acute-on-Chronic Liver Failure.
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DOI：
10.3390/cells9122632
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发表时间：
2020-12-08
期刊：
影响因子：
6
通讯作者：
Clària J
中科院分区：
文献类型：
--
作者：
Casulleras M;Zhang IW;López-Vicario C;Clària J
急性慢性肝衰竭（ACLF）是肝硬化患者发生的一种复杂综合征，其特征是急性代偿失代偿、器官衰竭和短期死亡率高。ACLF的发生通常与突发事件密切相关，如急性酒精性、药物性或病毒性肝炎或细菌感染，在没有突发事件的情况下，可能与细菌产物的肠道易位有关。免疫功能失衡是其发病机制和结果的核心，最初的过度全身炎症反应导致器官衰竭和死亡。这种高炎症状态最终会损害宿主免疫细胞的防御机制，使ACLF患者免疫功能低下，更容易发生继发性感染，从而导致更高的器官功能障碍和死亡率。在这篇综述中，我们描述了急性失代偿肝硬化发展为ACLF患者的高炎症状态的主要特征，特别强调了先天免疫系统细胞（即单核细胞和中性粒细胞）、它们的触发因素（病原体和损伤相关的分子模式[PAMPs和DAMPs]）、它们的效应分子（细胞因子、趋化因子、生长因子和生物活性脂质介质）以及对组织免疫病理学的影响。此外，本综述还包括一章讨论了基于多效蛋白（如白蛋白、toll样受体4拮抗剂、白细胞介素-22或干细胞治疗）调节白细胞功能的新疗法。最后，在不诱导免疫抑制的情况下，寻找一种适当的干预措施的重要性被强调为肝硬化治疗的主要挑战之一。
Acute-on-chronic liver failure (ACLF) is a complex syndrome that develops in patients with cirrhosis and is characterized by acute decompensation, organ failure(s) and high short-term mortality. ACLF frequently occurs in close temporal relationship to a precipitating event, such as acute alcoholic, drug-induced or viral hepatitis or bacterial infection and, in cases without precipitating events, probably related to intestinal translocation of bacterial products. Dysbalanced immune function is central to its pathogenesis and outcome with an initial excessive systemic inflammatory response that drives organ failure and mortality. This hyperinflammatory state ultimately impairs the host defensive mechanisms of immune cells, rendering ACLF patients immunocompromised and more vulnerable to secondary infections, and therefore to higher organ dysfunction and mortality. In this review, we describe the prevailing characteristics of the hyperinflammatory state in patients with acutely decompensated cirrhosis developing ACLF, with special emphasis on cells of the innate immune system (i.e., monocytes and neutrophils), their triggers (pathogen- and damage-associated molecular patterns [PAMPs and DAMPs]), their effector molecules (cytokines, chemokines, growth factors and bioactive lipid mediators) and the consequences on tissue immunopathology. In addition, this review includes a chapter discussing new emerging therapies based on the modulation of leukocyte function by the administration of pleiotropic proteins such as albumin, Toll-like receptor 4 antagonists, interleukin-22 or stem cell therapy. Finally, the importance of finding an appropriate intervention that reduces inflammation without inducing immunosuppression is highlighted as one of the main therapeutic challenges in cirrhosis.
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影响因子：
24.5
作者：
Bernsmeier C;Triantafyllou E;Brenig R;Lebosse FJ;Singanayagam A;Patel VC;Pop OT;Khamri W;Nathwani R;Tidswell R;Weston CJ;Adams DH;Thursz MR;Wendon JA;Antoniades CG
通讯作者：
Antoniades CG
影响因子：
29.4
作者：
BYL, B;ROUCLOUX, I;DEVIERE, J
通讯作者：
DEVIERE, J
影响因子：
4.2
作者：
Banares, Rafael;Ibanez-Samaniege, Luis;Arroyo, Vicente
通讯作者：
Arroyo, Vicente
影响因子：
24.5
作者：
Bernardi, Mauro;Angeli, Paolo;Arroyo, Vicente
通讯作者：
Arroyo, Vicente
影响因子：
168.9
作者：
Caraceni, Paolo;Riggio, Oliviero;Bernardi, Mauro
通讯作者：
Bernardi, Mauro