Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis
Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis
复制标题
DOI：
10.1016/j.jhep.2015.07.004
复制
发表时间：
2015-11-01
影响因子：
25.7
通讯作者：
Arroyo, Vicente
中科院分区：
文献类型：
--
作者：
Bernardi, Mauro;Moreau, Richard;Arroyo, Vicente
外周动脉血管扩张假说在肝硬化及其并发症领域最有影响力。它已经引起了数百个实验和人类肝硬化的病理生理学研究，是挽救生命治疗的理论基础。毫无疑问，内脏动脉血管舒张有助于门静脉高压症，是腹水和肝肾综合征等表现的基础，但该假说产生的研究发现，这些并发症的原始病理生理学解释存在差距。我们对调节血管张力、炎症和宿主-微生物群相互作用的机制的知识的扩展需要更广泛的方法来治疗晚期肝硬化，包括其整个表现谱。事实上，多器官功能障碍和衰竭可能是由复杂的相互作用引起的，其中细菌产物的全身传播是主要事件。随后宿主先天免疫应答的激活触发负责动脉血管舒张的内皮分子机制，并且还通过促炎细胞因子和活性氧和氮物质的风暴危害器官完整性。因此，晚期肝硬化的图像可以被看作是炎症综合征的结果，与简单的血流动力学紊乱相矛盾。(C)2015年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
The peripheral arterial vasodilation hypothesis has been most influential in the field of cirrhosis and its complications. It has given rise to hundreds of pathophysiological studies in experimental and human cirrhosis and is the theoretical basis of life-saving treatments. It is undisputed that splanchnic arterial vasodilation contributes to portal hypertension and is the basis for manifestations such as ascites and hepatorenal syndrome, but the body of research generated by the hypothesis has revealed gaps in the original pathophysiological interpretation of these complications. The expansion of our knowledge on the mechanisms regulating vascular tone, inflammation and the host-microbiota interaction require a broader approach to advanced cirrhosis encompassing the whole spectrum of its manifestations. Indeed, multiorgan dysfunction and failure likely result from a complex interplay where the systemic spread of bacterial products represents the primary event. The consequent activation of the host innate immune response triggers endothelial molecular mechanisms responsible for arterial vasodilation, and also jeopardizes organ integrity with a storm of pro-inflammatory cytokines and reactive oxygen and nitrogen species. Thus, the picture of advanced cirrhosis could be seen as the result of an inflammatory syndrome in contradiction with a simple hemodynamic disturbance. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.