The role of DNA Methylation as an epigenetic modifier of hepatic fibrosis progression in Non Alcoholic Fatty Liver Disease.

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Obesity and diabetes related Fatty Liver Disease is becoming the most common cause of liver disease worldwide. Whilst in most patients the liver remains unharmed, a significant number of patients progress to inflammation and scarring, which can ultimately lead to liver failure and liver cancer. At present, there is no way to predict who may develop inflammation and scarring, nor any effective treatment.My own recent work has suggested a theory that genes controlling scarring can be modified during our lifetime to influence the rate at which liver disease will progress.My proposal aims to extend my initial results; I will use liver samples from animals and patients to determine whether the modifications in genes change over the course of disease or whether they were present before advanced disease developed. I will assess where these gene changes arise in the liver, which other genes may be subject to this gene modification and whether it occurs in other cells in the body, specifically the blood.The results from this proposal are important and relevant to the patient; they will present opportunities to advance our understanding why some patients with fatty liver form scars, to predict those patients and to potentially treat liver scarring.