Dr Reenam Khan (Liver)

Institution: University of Birmingham

Title: Characterising a Novel Murine Model of Alcoholic Hepatitis

Project Start Date: 15 September 2017

Completion Date: 31 July 2018

Summary:

Alcoholic liver disease (ALD) is a major cause of liver disease and is becoming increasingly common. The number of deaths from ALD has risen five-fold in the last 30 years.  One way in which ALD can present is ‘alcoholic hepatitis’, which is characterised by inflammation in the liver caused by alcohol. Mild cases of alcoholic hepatitis may resolve if patients stop drinking alcohol. However, in severe cases, there is a high rate of death, particularly relating to infection (sepsis). Steroids and the drug pentoxiyfylline have been commonly recommended for treatment of severe alcoholic hepatitis. However, there is an urgent need to develop more effective new treatments, making alcoholic hepatitis an important area to research.

Using animals, such as mice, to investigate a disease is important to understand how the disease will develop in humans and to identify targets for treatment. However, it is essential to use an animal model that represents the human disease as closely as possible for the research to be useful. The challenge with alcoholic hepatitis is finding a good mouse model of the disease. This is part of the reason that there is relatively little research looking into new treatments for this debilitating condition.

Certain cells from the bone marrow, known as stem cells, have been shown to reduce inflammation in a number of diseases in animals and humans. There is an exciting possibility that these cells could also work in alcoholic hepatitis. However, researchers need to test these cells in a good mouse model of alcoholic hepatitis before they are given to human patients.

Dr Khan and her colleagues had developed a new mouse model of alcoholic hepatitis using genetic modification. They had done some tests which suggested that the disease in these mice has similar features to the disease in humans. For her Guts UK/BSG Trainee Award Dr Khan set off to do further tests to evaluate this mouse model of alcoholic hepatitis in more detail. The aim was to confirm that their mouse model is a good representation of human alcoholic hepatitis so they could then test the effectiveness of stem cells treatments in this model.

Dr Khan’s research showed that their mouse model could reproduce some of the key features of human disease. They also showed that the results were similar in a simpler mouse model without genetic modification, which simplifies future research efforts as these mice are easier to grow and maintain.

In the next steps of the research Dr Khan plans to obtain blood from patients with alcoholic hepatitis and compare features of mouse and human blood, to see how easily they can apply findings from the mice to patients.

Dr Khan also used the data and findings obtained from her Guts UK/BSG Trainee project to apply for funding to undertake a PhD, which she was awarded in September 2018. She now plans to use this mouse model in the testing of a new potential stem cell treatment for alcoholic hepatitis, as part of her PhD project. She also hopes that her work will benefit other researchers who are investigating why and how alcoholic hepatitis occurs, and to test new treatments.