The American journal of pathology · 2025
Current Therapeutic Targets for Alcohol-Associated Liver Disease.
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Zhang Mengmeng, Ji Jingjing, Song Jiayi, An Chenchen, Pei Wangxiang, Fan Qianwen, Zuo Li, Wang Hua
Аннотация
Alcohol-associated liver disease (ALD) is a progressive liver disorder induced by chronic excessive alcohol consumption, affecting approximately 3.5% of the global population. The clinical spectrum of ALD encompasses simple steatosis, alcoholic hepatitis, fibrosis, cirrhosis, and the potential development of hepatocellular carcinoma. The pathogenesis of ALD involves a complex interplay of factors, including direct cell damage caused by alcohol and its metabolites, hepatic inflammation, immune dysregulation, and oxidative stress. Additionally, alcohol-induced dysbiosis and the subsequent imbalance of gut homeostasis further exacerbate the progression of ALD. While nutritional support and abstinence from alcohol remain the cornerstones of ALD management, growing evidence supports the therapeutic potential of targeting key pathologic processes such as inflammation, cellular oxidative stress, lipid metabolism, and strategies that promote liver regeneration and inhibit fibrosis. Emerging treatment approaches aimed at modulating the gut-liver-brain axis and targeting innate immune cells offer promising new avenues for ALD therapy. For patients with end-stage ALD, liver transplantation remains the only viable treatment option. This review summarizes the current epidemiology, pathogenesis, pathophysiology, natural history, and recent advancements in the therapeutic management of ALD, with the goal of providing further insight into the treatment of ALD and improve patient outcomes.