Alcoholic liver disease: pathogenesis and new therapeutic targets.
Alcoholic liver disease: pathogenesis and new therapeutic targets.
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酒精性肝病：发病机制和新的治疗靶点。
DOI：
10.1053/j.gastro.2011.09.002
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发表时间：
2011-11
期刊：
影响因子：
29.4
通讯作者：
Bataller R
中科院分区：
文献类型：
--
作者：
Gao B;Bataller R
酒精性肝病（ALD）是世界范围内慢性肝病的主要病因，可导致纤维化和肝硬化。美国国家酒精滥用和酒精中毒研究所发布的最新监测报告显示，肝硬化是美国第12大死因，2007年共有29,925人死亡，其中48%与酒精有关。ALD包括单纯性脂肪变性、酒精性肝炎、纤维化、肝硬化和叠加性肝细胞癌。早期对该病发病机制的研究主要集中在乙醇代谢相关的氧化应激和谷胱甘肽耗竭、蛋氨酸代谢异常、营养不良以及激活库普弗细胞的内毒素的产生。我们回顾了最近的研究结果，这些研究表征了与ALD相关的特定细胞内信号通路、转录因子、先天免疫、趋化因子、表观遗传特征、microrna和干细胞，从而提高了我们对其发病机制的理解。尽管取得了这些进展，但目前还没有针对性的治疗方法。酒精性肝炎治疗的基础仍然与40年前一样：戒酒、营养支持和皮质类固醇。迫切需要开发新的以病理生理为导向的治疗方法。最近对人类样本和动物模型的转化研究已经确定了有希望的治疗靶点。
Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide and can lead to fibrosis and cirrhosis. The latest surveillance report published by the National Institute on Alcohol Abuse and Alcoholism showed that liver cirrhosis was the 12th leading cause of death in the United States, with a total of 29,925 deaths in 2007, 48% of which were alcohol related. The spectrum of ALD includes simple steatosis, alcoholic hepatitis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Early work on the pathogenesis of the disease focused on ethanol metabolism–associated oxidative stress and glutathione depletion, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. We review findings from recent studies that have characterized specific intracellular signaling pathways, transcriptional factors, aspects of innate immunity, chemokines, epigenetic features, microRNAs, and stem cells that are associated with ALD, improving our understanding of its pathogenesis. Despite this progress, no targeted therapies are available. The cornerstone of treatment for alcoholic hepatitis remains as it was 40 years ago: abstinence, nutritional support, and corticosteroids. There is an urgent need to develop new pathophysiology-oriented therapies. Recent translational studies of human samples and animal models have identified promising therapeutic targets.
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