Harrison-Findik Duygu Dee
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
World J Gastroenterol. 2007 Oct 7;13(37):4925-30. doi: 10.3748/wjg.v13.i37.4925.
Patients with alcoholic liver disease frequently exhibit increased body iron stores, as reflected by elevated serum iron indices (transferrin saturation, ferritin) and hepatic iron concentration. Even mild to moderate alcohol consumption has been shown to increase the prevalence of iron overload. Moreover, increased hepatic iron content is associated with greater mortality from alcoholic cirrhosis, suggesting a pathogenic role for iron in alcoholic liver disease. Alcohol increases the severity of disease in patients with genetic hemochromatosis, an iron overload disorder common in the Caucasian population. Both iron and alcohol individually cause oxidative stress and lipid peroxidation, which culminates in liver injury. Despite these observations, the underlying mechanisms of iron accumulation and the source of the excess iron observed in alcoholic liver disease remain unclear. Over the last decade, several novel iron-regulatory proteins have been identified and these have greatly enhanced our understanding of iron metabolism. For example, hepcidin, a circulatory antimicrobial peptide synthesized by the hepatocytes of the liver is now known to play a central role in the regulation of iron homeostasis. This review attempts to describe the interaction of alcohol and iron-regulatory molecules. Understanding these molecular mechanisms is of considerable clinical importance because both alcoholic liver disease and genetic hemochromatosis are common diseases, in which alcohol and iron appear to act synergistically to cause liver injury.
酒精性肝病患者常表现出体内铁储存增加，血清铁指标（转铁蛋白饱和度、铁蛋白）升高及肝铁浓度升高即反映了这一点。即便轻度至中度饮酒也已被证明会增加铁过载的患病率。此外，肝铁含量增加与酒精性肝硬化导致的更高死亡率相关，这表明铁在酒精性肝病中具有致病作用。酒精会加重遗传性血色素沉着症患者的病情，这是一种在白种人群中常见的铁过载疾病。铁和酒精各自都会引发氧化应激和脂质过氧化，最终导致肝损伤。尽管有这些观察结果，但酒精性肝病中铁蓄积的潜在机制以及所观察到的过量铁的来源仍不清楚。在过去十年中，已鉴定出几种新型铁调节蛋白，这些蛋白极大地增进了我们对铁代谢的理解。例如，肝脏肝细胞合成的循环抗菌肽铁调素，现在已知在铁稳态调节中起核心作用。本综述试图描述酒精与铁调节分子之间的相互作用。了解这些分子机制具有相当重要的临床意义，因为酒精性肝病和遗传性血色素沉着症都是常见疾病，其中酒精和铁似乎协同作用导致肝损伤。
