Alcohol use disorder (AUD) remains a significant public health concern, affecting around 5% of adults worldwide. Novel pathways of damage have been described during the last years, providing insight into the mechanism of injury due to alcohol misuse beyond the direct effect of ethanol byproducts on the liver parenchyma and neurobehavioral mechanisms. Thus, the gut-liver-brain axis and immune system involvement could be therapeutic targets for AUD. In particular, a change in gut microbiota composition and function, especially bile acid homeostasis, and these changes can improve after alcohol cessation. Alcohol can also directly disrupt intestinal and blood-brain barriers. Activation of the immune system can be triggered by intestinal barrier dysfunction and translocation of bacteria, pathogen-associated molecular patterns (such as lipopolysaccharide), cytokines, and damage-associated molecular patterns. These factors in turn promote liver and brain inflammation and progression of liver fibrosis. Other involved mechanisms include oxidative stress, apoptosis, autophagy, and the release of extracellular vesicles and miRNA from hepatocytes. Potential therapeutic targets include gut microbiota (probiotics and fecal microbiota transplantation), neuroinflammatory pathways, as well as neuroendocrine pathways, e.g.: the ghrelin system (ghrelin receptor blockade), incretin mimetics (GLP-1 analogs), and the mineralocorticoid receptor system (spironolactone). In addition, support with psychological and behavioral treatments is essential to address the multiple dimensions of AUD. In the future, a personalized approach considering these novel targets can contribute to significantly decreasing the alcohol-related burden of disease.

中文翻译：

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对戒酒和酒精相关性肝病复发的分子基础的新见解。

酒精使用障碍 (AUD) 仍然是一个重大的公共卫生问题，影响着全球约 5% 的成年人。在过去的几年中，人们描述了新的损伤途径，除了乙醇副产品对肝实质和神经行为机制的直接影响之外，还提供了对酒精滥用造成的损伤机制的深入了解。因此，肠-肝-脑轴和免疫系统参与可能是 AUD 的治疗靶点。特别是肠道微生物群组成和功能的变化，尤其是胆汁酸稳态，这些变化可以在戒酒后得到改善。酒精还会直接破坏肠道和血脑屏障。肠道屏障功能障碍和细菌易位、病原体相关分子模式（如脂多糖）、细胞因子和损伤相关分子模式可以触发免疫系统的激活。这些因素反过来促进肝脏和大脑炎症以及肝纤维化的进展。其他涉及的机制包括氧化应激、细胞凋亡、自噬以及肝细胞释放细胞外囊泡和 miRNA。潜在的治疗靶点包括肠道微生物群（益生菌和粪便微生物群移植）、神经炎症途径以及神经内分泌途径，例如：生长素释放肽系统（生长素释放肽受体阻断）、肠促胰素模拟物（GLP-1类似物）和盐皮质激素受体系统（螺内酯） ）。此外，心理和行为治疗的支持对于解决 AUD 的多个方面至关重要。未来，考虑这些新目标的个性化方法可以有助于显着减少与酒精相关的疾病负担。