Zakhari Samir, Li Ting-Kai
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9304, USA.
Hepatology. 2007 Dec;46(6):2032-9. doi: 10.1002/hep.22010.
More than 70% of alcohol is consumed by 10% of the population in the United States. Implicit in this statistic is that tremendous variation in the pattern of drinking (quantity, frequency, and duration) exists among alcohol consumers. Individuals who are binge or chronic drinkers will have different health outcomes than social drinkers. Therefore, knowing the pattern of drinking will shed light on how severely individuals are alcohol-dependent and on the extent of liver damage. Thus, these parameters assume particular relevance for the treatment-providing physician. Genetic factors contribute substantially to differences in alcohol metabolism. Variations in the activities of the alcohol-metabolizing enzymes, cytosolic alcohol dehydrogenase and mitochondrial aldehyde dehydrogenase, in part determine blood alcohol concentration, thereby contributing to the predisposition to becoming alcohol-dependent and to susceptibility to alcohol-induced liver damage. Chronic alcohol consumption induces cytochrome P450 2E1, a microsomal enzyme that metabolizes alcohol at high concentrations and also metabolizes medications such as acetaminophen and protease inhibitors. Alcohol metabolism changes the redox state of the liver, which leads to alterations in hepatic lipid, carbohydrate, protein, lactate, and uric acid metabolism. The quantity and frequency of alcohol consumption severely impact the liver in the presence of comorbid conditions such as infection with hepatitis B or C and/or human immunodeficiency virus, type 2 diabetes, hemochromatosis, or obesity and thus have implications with respect to the extent of injury and response to medications.
Knowledge of the relationships between the quantity, frequency, and patterns of drinking and alcoholic liver disease is limited. A better understanding of these relationships will guide hepatologists in managing alcoholic liver disease.
在美国,超过70%的酒精是由10%的人口消费的。这一统计数据背后隐含的是,酒精消费者的饮酒模式(饮酒量、饮酒频率和饮酒持续时间)存在巨大差异。暴饮或长期饮酒者与社交饮酒者的健康后果会有所不同。因此,了解饮酒模式将有助于了解个体酒精依赖的严重程度以及肝脏损伤的程度。因此,这些参数对于提供治疗的医生来说具有特别重要的意义。遗传因素在很大程度上导致了酒精代谢的差异。酒精代谢酶——胞质醇脱氢酶和线粒体醛脱氢酶——活性的变化,部分决定了血液中的酒精浓度,从而导致个体易于产生酒精依赖以及易受酒精性肝损伤影响。长期饮酒会诱导细胞色素P450 2E1,这是一种微粒体酶,在高浓度下代谢酒精,也代谢对乙酰氨基酚和蛋白酶抑制剂等药物。酒精代谢会改变肝脏的氧化还原状态,进而导致肝脏脂质、碳水化合物、蛋白质、乳酸和尿酸代谢的改变。在合并感染乙型或丙型肝炎和/或人类免疫缺陷病毒、2型糖尿病、血色素沉着症或肥胖症等疾病的情况下,饮酒量和饮酒频率会严重影响肝脏,因此对损伤程度和药物反应也有影响。
关于饮酒量、饮酒频率和饮酒模式与酒精性肝病之间关系的了解有限。更好地理解这些关系将指导肝病学家管理酒精性肝病。