Cell death and cell death responses in liver disease: mechanisms and clinical relevance.
Cell death and cell death responses in liver disease: mechanisms and clinical relevance.
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DOI：
10.1053/j.gastro.2014.07.018
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发表时间：
2014-10
期刊：
影响因子：
29.4
通讯作者：
Schwabe RF
中科院分区：
文献类型：
--
作者：
Luedde T;Kaplowitz N;Schwabe RF
肝细胞死亡存在于几乎所有类型的人类肝脏疾病中，并且用作检测病毒性、毒性、代谢或自身免疫性起源的急性和慢性肝脏疾病的敏感参数。临床数据和动物模型表明，肝细胞死亡是肝脏疾病进展的关键触发因素，表现为随后发生炎症、纤维化、肝硬化和肝细胞癌。肝细胞死亡的模式在肝脏疾病之间有很大的不同。不同的细胞死亡模式，如细胞凋亡、坏死和坏死性凋亡，通过不同的机制触发特异性细胞死亡反应并促进肝脏疾病的进展。在这篇综述中，我们首先讨论了不同的细胞死亡模式，损伤相关的分子模式和特定的细胞死亡反应有助于肝脏疾病的发展的分子机制。然后，我们回顾了细胞死亡的临床相关性，重点是生物标志物;细胞死亡对药物诱导的，病毒性的和脂肪肝疾病和肝癌的贡献;以及细胞死亡途径作为治疗靶点的证据。
Hepatocellular death is present in almost all types of human liver disease and is used as a sensitive parameter for the detection of acute and chronic liver disease of viral, toxic, metabolic, or autoimmune origin. Clinical data and animal models suggest that hepatocyte death is the key trigger of liver disease progression, manifested by the subsequent development of inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Modes of hepatocellular death differ substantially between liver diseases. Different modes of cell death such as apoptosis, necrosis, and necroptosis trigger specific cell death responses and promote progression of liver disease through distinct mechanisms. In this review, we first discuss molecular mechanisms by which different modes of cell death, damage-associated molecular patterns, and specific cell death responses contribute to the development of liver disease. We then review the clinical relevance of cell death, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets.