Mechanisms and cell signaling in alcoholic liver disease.
Mechanisms and cell signaling in alcoholic liver disease.
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DOI：
10.1515/bc.2010.137
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发表时间：
2010-11
影响因子：
3.7
通讯作者：
McClain CJ
中科院分区：
文献类型：
--
作者：
Beier JI;McClain CJ
酒精性肝病（ALD）仍然是世界范围内发病率和死亡率的主要原因。例如，退伍军人管理局合作研究报告说，肝硬化和酒精性肝炎叠加的患者4年死亡率> 60%。ALD的不良预后意味着预防疾病进展比治疗终末期肝病更有效。一个明显的预防途径是去除有害物质;然而，酗酒者臭名昭著的高再犯率使得保持禁欲成为预防ALD的一个困难的治疗目标。事实上，虽然ALD的进展是很好的特征，但没有普遍接受的治疗方法可以阻止或逆转人类的这一过程。随着对机制和介导ALD发生和进展的危险因素的更好理解，可以开发合理的靶向治疗来治疗或预防ALD。这篇综述的目的是总结慢性酒精滥用损害肝脏的既定和拟议机制，并强调已知或假设介导这些影响的关键信号事件。
Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. The poor prognosis of ALD implies that preventing disease progression would be more effective than treating end-stage liver disease. An obvious avenue of prevention would be to remove the damaging agent; however, the infamously high rate of recidivism in alcoholics makes maintaining abstinence a difficult treatment goal to prevent ALD. Indeed, although the progression of ALD is well-characterized, there is no universally accepted therapy available to halt or reverse this process in humans. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of ALD, rational targeted therapy can be developed to treat or prevent ALD. The purpose of this review is to summarize the established and proposed mechanisms by which chronic alcohol abuse damages the liver and to highlight key signaling events known or hypothesized to mediate these effects.