当前酒精相关性肝病的治疗靶点

IF 3.6 2区 医学 Q1 PATHOLOGY
Mengmeng Zhang, Jingjing Ji, Jiayi Song, Chenchen An, Wangxiang Pei, Qianwen Fan, Li Zuo, Hua Wang
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引用次数: 0

摘要

ALD是一种由慢性过量饮酒引起的肝脏疾病,影响全球约3.5%的人口。ALD包括单纯性脂肪变性、酒精性肝炎、纤维化、肝硬化和潜在的肝细胞癌。ALD的发病机制涉及多种因素的复杂相互作用,包括酒精及其代谢物引起的直接细胞损伤、肝脏炎症、免疫失调和氧化应激。此外,生态失调和随后的肠道稳态失衡进一步加剧了ALD的进展。虽然戒酒和营养支持仍然是ALD治疗的基石,但越来越多的证据强调了针对各种病理过程的治疗潜力,特别是炎症、细胞氧化应激、脂质代谢和促进肝脏再生和抑制纤维化的策略。此外,旨在调节肠-肝-脑轴和靶向先天免疫细胞的新兴治疗方法为ALD治疗提供了有希望的新途径。对于终末期酒精性肝病患者,肝移植仍然是改善预后的唯一可行选择。本文综述了ALD的流行病学、发病机制、病理生理学、自然史以及治疗管理方面的最新进展,旨在为ALD的治疗提供进一步的见解,并改善患者的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
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.
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