酒精性肝炎相关的慢加急性肝衰竭  

Acute-on-chronic liver failure associated with alcoholic hepatitis

作　　者：闵颖 佟静[2] 王炳元[2] Min Ying;Tong Jing;Wang Bingyuan(Department of Alcohol-related Liver Diseases,Tongliao Infectious Disease Hospital,Inner Mongolia,Tongliao 028000,China;Department of Gastroenterology,the First Affliated Hospital of China Medical University,Liaoning,Shenyang 110001,China)

机构地区：[1]内蒙古自治区通辽市传染病医院酒精性肝病科,内蒙古自治区通辽028000 [2]中国医科大学附属第一医院消化内科,辽宁沈阳110001

出　　处：《中国医学前沿杂志（电子版）》2023年第2期12-17,共6页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

基　　金：国家青年自然科学基金项目(81700453)。

摘　　要：酒精性肝炎是一种急性炎症性肝病,常常发生于酒精性肝硬化背景下,与短期和长期的高发病率和死亡率有关,特别是合并重症急性酒精性肝炎时。重症急性酒精性肝炎是一种与过量饮酒相关的独特临床综合征。过量饮酒会导致肠道微生物组构成改变及肠道通透性增加,形成酒精性肝炎的中心介质肠源性病原体相关分子模式(pathogen associated molecular patterns,PAMP)。酒精及其代谢物通过线粒体损伤和内质网应激诱导活性氧的产生和肝细胞损伤。肝细胞损伤激活凋亡和坏死途径并释放损伤相关分子模式(damage associated molecular patterns,DAMP),放大并持续炎症反应。DAMP和PAMP在肝脏中的累积,触发细胞因子的大量释放,并通过免疫介导的凋亡和坏死转变为肝细胞非凋亡性程序性细胞死亡(细胞焦亡),细胞焦亡增强免疫细胞的免疫原性,诱导发生严重的全身性炎症反应综合征(systemic inflammatory response syndrome,SIRS)。与此同时,为了抵消过度的SIRS,机体逐渐产生代偿性抗炎反应综合征(compensatory anti-inflammatory response syndrome,CARS),试图从过度炎症状态中拯救体内平衡,结果导致重要的先天性和适应性免疫系统细胞的衰竭和功能障碍,发生功能性免疫细胞瘫痪,从而增加感染风险。SIRS和CARS并行发展,以及诱发的脓毒症,最终导致慢加急性肝衰竭和肝外器官衰竭。Alcoholic hepatitis is an acute inflammatory liver disease that often occurs in a background of alcoholic cirrhosis and is associated with high short-and long-term morbidity and mortality,especially in severe acute alcohol-related hepatitis(SAAH).SAAH is a distinct clinical syndrome associated with excessive alcohol consumption.Excessive alcohol consumption can change gut microbiome composition,increase intestinal permeability,and produce gut-derived pathogen-associated molecular patterns(PAMP),which is a central mediator of inflammation in alcoholic hepatitis.Alcohol and its metabolites induce reactive oxygen species and hepatocyte injury,through mitochondrial damage and endoplasmic reticulum stress.Hepatocyte injury activates apoptotic and necrotic pathways and releases damage-associated molecular patterns(DAMP)that amplify and sustain the inflammatory response.The accumulation of DAMP and PAMP in the liver triggers a massive release of cytokines and transforms into non-apoptotic programmed cell death(pyroptosis),which enhances the immunogenicity of immune cells and induces inflammatory cascade reaction until severe systemic inflammatory response syndrome(SIRS)occurs.At the same time,body gradually produces compensatory anti-inflammatory response syndrome(CARS),trying to counteract the high-grade SIRS.As a result,innate and adaptive immune cells are exhausted and dysfunctional,leading to a functional paralysis of immune cells and increased risk of sepsis.SIRS,CARS,and induced sepsis ultimately cause acute-on-chronic liver failure and extrahepatic organ failure.

关 键 词：酒精性肝病 全身性炎症反应综合征 代偿性抗炎反应综合征 慢加急性肝衰竭 

分 类 号：R575.1[医药卫生—消化系统]