Alcohol-associated liver disease (ALD) is one of the major diseases arising from chronic alcohol consumption and is one of the most common causes of liver-related morbidity and mortality. ALD includes asymptomatic liver steatosis, fibrosis, cirrhosis, and alcohol-associated hepatitis and its complications. The progression of ALD involves complex cell-cell and organ-organ interactions. We focus on the impact of alcohol on dysregulation of homeostatic mechanisms and regulation of injury and repair in the liver. In particular, we discuss recent advances in understanding the disruption of balance between programmed cell death and prosurvival pathways, such as autophagy and membrane trafficking, in the pathogenesis of ALD. We also summarize current understanding of innate immune responses, liver sinusoidal endothelial cell dysfunction and hepatic stellate cell activation, and gut-liver and adipose-liver cross talk in response to ethanol. In addition,we describe the current potential therapeutic targets and clinical trials aimed at alleviating hepatocyte injury, reducing inflammatory responses, and targeting gut microbiota, for the treatment of ALD.

中文翻译：

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酒精相关性肝病发病机制的最新进展

酒精相关性肝病（ALD）是长期饮酒引起的主要疾病之一，也是肝脏相关发病和死亡的最常见原因之一。 ALD包括无症状的肝脏脂肪变性、纤维化、肝硬化和酒精相关性肝炎及其并发症。 ALD 的进展涉及复杂的细胞-细胞和器官-器官相互作用。我们重点研究酒精对体内平衡机制失调以及肝脏损伤和修复调节的影响。我们特别讨论了在 ALD 发病机制中程序性细胞死亡和促生存途径（例如自噬和膜运输）之间平衡被破坏的最新进展。我们还总结了目前对先天免疫反应、肝窦内皮细胞功能障碍和肝星状细胞激活以及对乙醇反应的肠-肝和脂肪-肝交互作用的理解。此外，我们还描述了目前旨在减轻肝细胞损伤、减少炎症反应和针对肠道微生物群来治疗 ALD 的潜在治疗靶点和临床试验。