Advances in alcoholic liver disease.
Advances in alcoholic liver disease.
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DOI：
10.1007/s11894-010-0157-5
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发表时间：
2011-02
影响因子：
--
通讯作者：
McClain CJ
中科院分区：
文献类型：
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作者：
Beier JI;Arteel GE;McClain CJ
酒精性肝病（ALD）仍然是美国肝病死亡的主要原因。美国退伍军人管理局的研究显示，肝硬化合并酒精性肝炎患者在 4 年内的死亡率超过 60%，其中大多数死亡发生在第一个月。因此，这种疾病的预后比许多常见类型的癌症（例如乳腺癌、前列腺癌和结肠癌）更为不利。此外，ALD 还因工资损失、医疗保健费用和生产力损失而造成重大经济负担。不幸的是，对于 ALD 的任何阶段，仍然没有美国食品和药物管理局批准或广泛接受的药物治疗。因此，迫切需要更详细地了解肝损伤机制。本文回顾了与 ALD 直接相关的五个主要领域的机制和治疗的最新进展：氧化应激；肠-肝轴和细胞因子信号传导；营养不良；纤维蛋白/凝血；和星状细胞活化/纤维化。我们还回顾了为什么与这些机制相关的疗法在实验动物和体外系统中表现良好，但不一定转化为对人类 ALD 的有效疗法。
Alcoholic liver disease (ALD) remains a leading cause of death from liver disease in the United States. In studies from the Veterans Administration, patients with cirrhosis and superimposed alcoholic hepatitis had greater than 60% mortality over a 4-year period, with most of those deaths occurring in the first month. Thus, the prognosis for this disease is more ominous than for many common types of cancer (eg, breast, prostate, and colon). Moreover, ALD imposes a significant economic burden from lost wages, health care costs, and lost productivity. Unfortunately, there is still no Food and Drug Administration–approved or widely accepted drug therapy for any stage of ALD. Thus, a pressing need exists for a more detailed understanding of mechanisms of liver injury. This article reviews recent advances in mechanisms and therapy related to five major areas of direct relevance to ALD: oxidative stress; gut-liver axis and cytokine signaling; malnutrition; fibrin/clotting; and stellate cell activation/fibrosis. We also review why therapies related to these mechanisms have performed well in experimental animals and in vitro systems, but have not necessarily translated into effective therapy for humans with ALD.