Mengmeng Zhang, Jingjing Ji, Jiayi Song, Chenchen An, Wangxiang Pei, Qianwen Fan, Li Zuo, Hua Wang
{"title":"当前酒精相关性肝病的治疗靶点","authors":"Mengmeng Zhang, Jingjing Ji, Jiayi Song, Chenchen An, Wangxiang Pei, Qianwen Fan, Li Zuo, Hua Wang","doi":"10.1016/j.ajpath.2025.06.009","DOIUrl":null,"url":null,"abstract":"<p><p>ALD is a liver disorder induced by chronic excessive alcohol consumption, affecting approximately 3.5% of the global population. The 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 cellular damage caused by alcohol and its metabolites, hepatic inflammation, immune dysregulation, and oxidative stress. Additionally, dysbiosis and the subsequent imbalance of gut homeostasis further exacerbate the progression of ALD. While abstinence from alcohol and nutritional support remain the cornerstone of ALD management, increasing evidence highlights the therapeutic potential of targeting various pathological processes, in particular inflammation, cellular oxidative stress, lipid metabolism, and strategies to promote liver regeneration and inhibit fibrosis. Moreover, 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 alcoholic liver disease, liver transplantation remains the only viable option to improve prognosis. This review summarizes the current epidemiology, pathogenesis, pathophysiology, natural history, and recent advancements in the therapeutic management of ALD, aiming to provide further insights into the treatment of ALD and improve patient outcomes.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Current Therapeutic targets for Alcohol-associated liver disease.\",\"authors\":\"Mengmeng Zhang, Jingjing Ji, Jiayi Song, Chenchen An, Wangxiang Pei, Qianwen Fan, Li Zuo, Hua Wang\",\"doi\":\"10.1016/j.ajpath.2025.06.009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>ALD is a liver disorder induced by chronic excessive alcohol consumption, affecting approximately 3.5% of the global population. The 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 cellular damage caused by alcohol and its metabolites, hepatic inflammation, immune dysregulation, and oxidative stress. Additionally, dysbiosis and the subsequent imbalance of gut homeostasis further exacerbate the progression of ALD. While abstinence from alcohol and nutritional support remain the cornerstone of ALD management, increasing evidence highlights the therapeutic potential of targeting various pathological processes, in particular inflammation, cellular oxidative stress, lipid metabolism, and strategies to promote liver regeneration and inhibit fibrosis. Moreover, 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 alcoholic liver disease, liver transplantation remains the only viable option to improve prognosis. This review summarizes the current epidemiology, pathogenesis, pathophysiology, natural history, and recent advancements in the therapeutic management of ALD, aiming to provide further insights into the treatment of ALD and improve patient outcomes.</p>\",\"PeriodicalId\":7623,\"journal\":{\"name\":\"American Journal of Pathology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ajpath.2025.06.009\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ajpath.2025.06.009","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
Current Therapeutic targets for Alcohol-associated liver disease.
ALD is a liver disorder induced by chronic excessive alcohol consumption, affecting approximately 3.5% of the global population. The 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 cellular damage caused by alcohol and its metabolites, hepatic inflammation, immune dysregulation, and oxidative stress. Additionally, dysbiosis and the subsequent imbalance of gut homeostasis further exacerbate the progression of ALD. While abstinence from alcohol and nutritional support remain the cornerstone of ALD management, increasing evidence highlights the therapeutic potential of targeting various pathological processes, in particular inflammation, cellular oxidative stress, lipid metabolism, and strategies to promote liver regeneration and inhibit fibrosis. Moreover, 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 alcoholic liver disease, liver transplantation remains the only viable option to improve prognosis. This review summarizes the current epidemiology, pathogenesis, pathophysiology, natural history, and recent advancements in the therapeutic management of ALD, aiming to provide further insights into the treatment of ALD and improve patient outcomes.
期刊介绍:
The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.