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

肥胖和糖尿病相关的脂肪肝正在成为全球肝病最常见的原因。虽然在大多数患者中，肝脏仍然没有受到伤害，但大量患者会发展为炎症和瘢痕，最终可能导致肝功能衰竭和肝癌。目前，没有办法预测谁可能会出现炎症和疤痕，也没有任何有效的治疗方法。我自己最近的工作提出了一种理论，即控制疤痕的基因可以在我们的一生中进行修饰，以影响肝脏疾病的进展速度。我的提议旨在扩展我的初步结果;我将使用动物和患者的肝脏样本来确定基因的修饰是否在疾病过程中发生变化，或者它们是否在晚期疾病发展之前就存在。我将评估这些基因变化在肝脏中的位置，哪些其他基因可能受到这种基因修饰，以及它是否发生在身体的其他细胞中，特别是血液中。这项提议的结果对患者来说是重要的和相关的;它们将为我们提供机会，以促进我们理解为什么一些脂肪肝患者会形成疤痕，预测这些患者并潜在地治疗肝脏疤痕。

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.