ALCOHOL-ASSOCIATED LIVER DISEASE: NATURAL HISTORY, MANAGEMENT AND NOVEL TARGETED THERAPIES.

IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Clinical and Molecular Hepatology Pub Date : 2024-10-31 DOI:10.3350/cmh.2024.0709
Edilmar Alvarado-Tapias, Elisa Pose, Jordi Gratacós, Ana Clemente-Sánchez, Hugo Hugo López-Pelayo, Ramón Bataller
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Abstract

Alcohol consumption is a leading cause of preventable morbidity and mortality worldwide and the primary cause of advanced liver disease. Alcohol use disorder (AUD) is a chronic, frequently relapsing condition characterized by persistent alcohol consumption despite its negative consequences. Alcohol-associated liver disease (ALD) encompasses a series of stages, from fatty liver (steatosis) to inflammation (steatohepatitis), fibrosis, and, ultimately, liver cirrhosis and its complications. The development of ALD is complex, involving both genetic and environmental factors, yet the exact mechanisms at play remain unclear. Alcohol-associated hepatitis (AH), a severe form of ALD, presents with sudden jaundice and liver failure. Currently, there are no approved targeted therapies able to interfere in the pathogenesis of ALD to stop the progression of the disease, making alcohol abstinence the most effective way to improve prognosis across all stages of ALD. For patients with advanced ALD who do not respond to medical therapy, liver transplantation is the only option that can improve prognosis. Recently, AH has become an early indication for liver transplantation in non-responders to medical treatment, showing promising results in carefully selected patients. This review provides an update on the epidemiology, natural history, pathogenesis, and current treatments for ALD. A deeper insight into novel targeted therapies investigated for AH focusing on new pathophysiologically-based agents is also discussed, including anti-inflammatory and antioxidative stress drugs, gut-liver axis modulators, and hepatocyte regenerative molecules.

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酒精相关肝病:自然史、管理和新型靶向疗法。
饮酒是全球可预防的发病率和死亡率的主要原因,也是晚期肝病的主要病因。酒精使用障碍(AUD)是一种慢性、经常复发的疾病,其特点是尽管会产生不良后果,但仍持续饮酒。酒精相关性肝病(ALD)包括一系列阶段,从脂肪肝(脂肪变性)到炎症(脂肪性肝炎)、纤维化,最终发展为肝硬化及其并发症。ALD 的发展过程十分复杂,涉及遗传和环境因素,但其确切的作用机制仍不清楚。酒精相关性肝炎(AH)是 ALD 的一种严重形式,表现为突发性黄疸和肝功能衰竭。目前,还没有获批的靶向疗法能够干预 ALD 的发病机制以阻止疾病进展,因此戒酒成为改善 ALD 各个阶段预后的最有效方法。对于药物治疗无效的晚期ALD患者来说,肝移植是改善预后的唯一选择。最近,AH已成为药物治疗无反应患者进行肝移植的早期适应症,在精心挑选的患者中显示出良好的效果。本综述介绍了ALD的流行病学、自然史、发病机制和当前治疗方法的最新进展。此外,文章还深入探讨了针对急性肝病研究的新型靶向疗法,重点关注基于病理生理学的新药物,包括抗炎和抗氧化应激药物、肠肝轴调节剂和肝细胞再生分子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical and Molecular Hepatology
Clinical and Molecular Hepatology Medicine-Hepatology
CiteScore
15.60
自引率
9.00%
发文量
89
审稿时长
10 weeks
期刊介绍: Clinical and Molecular Hepatology is an internationally recognized, peer-reviewed, open-access journal published quarterly in English. Its mission is to disseminate cutting-edge knowledge, trends, and insights into hepatobiliary diseases, fostering an inclusive academic platform for robust debate and discussion among clinical practitioners, translational researchers, and basic scientists. With a multidisciplinary approach, the journal strives to enhance public health, particularly in the resource-limited Asia-Pacific region, which faces significant challenges such as high prevalence of B viral infection and hepatocellular carcinoma. Furthermore, Clinical and Molecular Hepatology prioritizes epidemiological studies of hepatobiliary diseases across diverse regions including East Asia, North Asia, Southeast Asia, Central Asia, South Asia, Southwest Asia, Pacific, Africa, Central Europe, Eastern Europe, Central America, and South America. The journal publishes a wide range of content, including original research papers, meta-analyses, letters to the editor, case reports, reviews, guidelines, editorials, and liver images and pathology, encompassing all facets of hepatology.
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