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
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 have been able to develop a new mouse model of alcoholic hepatitis. They have done some tests which suggest that the disease in these mice has similar features to the disease in humans. The researchers need to do further tests to evaluate this mouse model of alcoholic hepatitis in more detail. They will measure changes in the liver and examine what happens to the activity of various genes that are involved in causing inflammation. They will also measure the degree of scarring in the liver tissue (fibrosis), and the degree to which the liver cells regenerate to replace damaged liver tissue.
Once the researchers confirm that the mouse model is a good representation of human disease, they plan to use this model to test the effectiveness of stem cells in treating alcoholic hepatitis. The researchers hope that the development of a good animal model of disease will help clarify how alcoholic hepatitis occurs, which in turn will help to identify and test new treatment targets.
Depending on the results of this preliminary work, the research group plans to inject the mice with stem cells obtained from human bone marrow, to see whether this can treat alcoholic hepatitis. If those results are promising they will then test the cells in human patients. The ultimate long-term goal of their work is to facilitate the development of strategies that reduce the high death rate, and increase the likelihood of complete recovery, in patients with alcoholic hepatitis.
I am delighted that CORE has agreed to fund this project, which will ultimately facilitate research into new treatments for alcoholic hepatitis.Dr Reenam Khan