Metabonomic and genetic profiling in severe alcoholic hepatitis

肝病是英国死亡率和发病率上升的唯一主要原因。酒精性肝病（ALD）占肝脏相关死亡的一半以上。它正在影响越来越年轻的患者。10年来，30岁以下的相关住院人数增加了一倍多。酒精通过引发炎症引起肝脏疾病，随着时间的推移，这会导致肝脏严重的瘢痕形成，称为肝硬化。肝硬化患者可能会出现黄疸和肝功能衰竭，这被称为失代偿。一些过度饮酒的患者，无论是否有肝硬化，都会出现严重的炎症，导致肝功能衰竭非常迅速。这种情况被称为酒精性肝炎。失代偿性肝硬化与酒精性肝炎很难区分，因为这两种情况看起来非常相似，这样做可能需要肝活检。酒精性肝炎患者有很高的死亡风险，因此，酒精性肝炎的治疗是非常重要的。尽管有最好的治疗，这些患者中约有三分之一将在一个月内死亡。目前可用的治疗方法有显着的副作用，似乎只在一些患者中起作用。目前，很难准确识别哪些患者愿意接受当前治疗，哪些患者不会对当前治疗产生反应。尽管许多人饮酒过量，但并非所有人都会患上肝硬化或酒精性肝炎。对双胞胎的研究表明，人们的基因可以部分解释这一点。然而，事实证明，很难确定可能使个体易受酒精诱导的肝损伤影响的特定基因变化。伦敦帝国理工学院的研究人员在Mark Thursz教授的领导下，正在利用先进的血液样本分析技术研究酒精性肝炎患者的代谢。他们将比较不同患者组的结果，以确定识别酒精性肝炎患者的特定变化。同时，在纽卡斯尔大学、伦敦大学学院和剑桥桑格研究所的研究人员的帮助下，同一个小组将研究过量饮酒患者的DNA序列。这些患者中约有一半患有酒精性肝炎，其余的没有肝脏疾病。这项大型研究将有助于确定基因的变化，这些基因的变化在饮酒过量时易导致肝脏损伤。这项研究的结果将为深入了解这种疾病铺平道路，为更好的诊断铺平道路，并有机会为这种疾病开发新的治疗方法。

Liver disease is the only major cause of mortality and morbidity on the rise in the United Kingdom. Alcoholic liver disease (ALD) accounts for over half of liver related deaths. It is affecting younger and younger patients. Related hospital admissions for those under 30 have more than doubled over 10 years. Alcohol causes liver disease by triggering inflammation, over time this leads to severe scarring of the liver called cirrhosis. Patients with cirrhosis may develop jaundice and liver failure; this is called decompensation. Some patients who drink alcohol excessively, with or without cirrhosis, develop severe inflammation, which leads to liver failure very rapidly. This condition is called alcoholic hepatitis. It can be very difficult to tell decompensated cirrhosis from alcoholic hepatitis, as the two conditions look very similar, doing so may require a liver biopsy. It is important to be able to tell them apart, as the treatment is different.Patients with alcoholic hepatitis have a high risk of death. Despite the best medical treatments approximately one-third of these patients will die within a month. Currently available treatments for the condition have significant side effects and only appear to work in some patients. At the present time it is difficult to accurately identify those patients who will and those patients who will not respond to current treatments.Although many people drink alcohol to excess not all of them develop cirrhosis or alcoholic hepatitis. Studies following twins have shown that people's genes can partly explain this. It has proven difficult however to identify the specific genetic changes which may make an individual susceptible to alcohol-induced liver damage.Researchers at Imperial College London, led by Professor Mark Thursz, are studying the metabolism of patients who develop alcoholic hepatitis using advanced techniques to analyse blood samples. They will compare the results from different groups of patients to identify specific changes that identify patients with alcoholic hepatitis. They will also see if it is possible to predict which patients with alcoholic hepatitis will do well with treatment.At the same time, with the help of researchers based at Newcastle University, University College London and the Sanger Institute in Cambridge, the same group will look at DNA sequences from patients who drink alcohol to excess. Around half of these patients have alcoholic hepatitis and the remainder have no liver disease. This large study will help to identify the changes in genes that are important in predisposing individuals to liver damage if they drink too much.The results of this research will provide insights into the disease and pave the way for better diagnosis and the opportunity to develop novel treatments for the condition, which are badly needed.