Metabonomic and genetic profiling in severe alcoholic hepatitis

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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.