Dr Ashwin Dhanda (Liver)
Institution: Plymouth University Peninsula School of Medicine
Title: Can assessment of global immune function predict outcome and response to corticosteroid treatment in patients with severe alcoholic hepatitis?
Project Start Date: 16th October 2017
Completion Date: 15th October 2018
Alcoholic hepatitis is a serious condition caused by long-term heavy alcohol consumption. It accounts for around 2% of all hospital admissions. If severe, it leads to liver failure and death in nearly 1 in 3. Only steroid treatment improves survival but around 1 in 3 do not respond and have a very high chance of dying from their condition. Moreover, steroid treatment has side effects, such as an increase in the risk of developing a serious infection. It is therefore important to be able to predict an individual patient’s response to steroids. This will allow patients to be selected for steroid treatment who are likely to benefit while avoiding unnecessary exposure of steroids and their risk of infection to those who are not. Steroid resistant patients could therefore be identified at an early stage of their hospital admission and offered alternative treatment including enrolment in trials of novel therapies. This will improve personalised patient care and the chance of survival from this condition.
Dr Dhanda and his colleagues had previously shown that a blood test accurately measured response to steroids in most patients. However this particular test was difficult to perform and could not be used in the NHS so there was a need to develop another test that can be used in a clinical setting. To develop a simpler test Dr Dhanda and his colleagues looked at how the immune system behaved in patients with severe alcoholic hepatitis who received steroid treatment. In particular they looked at markers of inflammation produced by certain types of white blood cells. Dr Dhanda and his colleagues noted that there was a difference in the levels of one particular marker of inflammation between patients who responded well to steroid treatment and those who did not. This difference in levels could be exploited in a new test, which was already commercially available and normally used for a different condition (to check the immune response of patients who had received an organ transplant). From this vantage point Dr Dhanda use this Guts UK and BSG pilot study to investigate whether this new test can be used to predict response to steroid treatment, and therefore chances of survival, of patients with alcoholic hepatitis.
For the study Dr Dhanda recruited patients with severe alcoholic hepatitis from the South West Liver Unit at Plymouth Hospitals NHS Trust and performed laboratory work in Plymouth University Peninsula School of Medicine. Dr Dhanda took blood samples from those patients and used the commercially-available blood test to measure markers of inflammation in the blood. He then followed up these patients for 3 months to find out whether the test measurement could predict their survival at that time.
Dr Dhanda found that out of patients who participated in this study, the two who did not respond to steroids and went on to die from alcoholic hepatitis had the lowest levels of the inflammation marker measured by the blood test. This suggests that the this blood test could be helpful to predict survival of patients with alcoholic hepatitis.
After getting these encouraging results from this pilot study, Dr Dhanda’s next step is to confirm this finding in a larger group of patients in the UK. He and his colleagues have already secured other funding to carry out the study in 200 additional patients with alcoholic hepatitis, which will start later in 2019. If their finding is confirmed in this next study, it will be easy to bring this test into routine NHS care to help guide patient treatment. Patients who do not respond to steroids and who have the highest chance of dying will be identified using this blood test when they arrive in hospital. Instead of steroids, they can be offered alternative treatment, which will improve patient care and may reduce the number of deaths from alcoholic hepatitis.
I would like to thank Guts UK for its generous support of this project. I hope that this project will ultimately improve survival of patients with alcoholic hepatitis, a serious condition leading to liver failure and death in up to 1 in 3. By using a simple blood test to measure immune function we will look for a marker that can predict survival of these patients. If successful, this blood test can be incorporated into everyday clinical practice to guide treatment options.Dr Ashwin Dhanda