Dr Palak Trivedi from the University of Birmingham will investigate whether immunotherapy could hold promise for controlling liver damage in patients with AIH.
“There is evidence that in people with AIH, the body’s protective mechanisms are duped and do not work properly. The exact disturbance is unclear, but we think there’s a reduced function of potentially protective immune cell types (called regulatory T cells, or ‘Treg’) and an increased number and function of cells that drive inflammation (effector T cells). The key question is: how do we restore the balance between protective cell types and the ones that drive inflammation?”
In his study, Dr Trivedi will investigate whether injections of Treg can control liver damage caused by the body’s immune system. Previous work from the Birmingham research group has shown that Treg can be taken from patients, enhanced in the lab, and safely returned by injection, with a quarter of the injected cells travelling back to the inflamed liver.
“The next step is to understand whether Treg still function as a protective cell type once they get to the liver, and whether they remain stable long enough to control tissue-damaging cell types.
“My project will take Treg from patients awaiting a liver transplant, then enhance and populate them in the lab. When patients undergo their liver transplant, we’ll inject Treg back into the damaged liver which has been removed during the operation. From a research perspective, studying the damaged liver in the lab - in real time - to examine the function of these cell types, is a world-first approach. It will offer vital clues for future research into whether Treg could benefit patients clinically.
“We want to take a targeted treatment approach, which homes in on the liver and gives the body the type of immune cells it needs to keep the fine balance of protective and inflammatory cells in check.”
Dr Trivedi’s work could then be used to identify and treat patients much earlier, and eventually be used to minimise the volume of medicines patients need, and prevent progression to liver failure.
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Autoimmune disease - Liver disease
Why is there a need to fund new research?
Autoimmune hepatitis (AIH) is a rare cause of long-term hepatitis in which the body’s immune system attacks and damages the liver. There are thought to be around 10,000 people living with autoimmune hepatitis in the UK, and although both men and women can develop the condition, it is more common in young women. It is not currently clear what causes AIH or whether anything can be done to prevent it.
Existing treatments for AIH aim to reduce inflammation by suppressing the immune system, but this can also reduce the immune system’s ability to fight infection. Current treatments do not provide a cure; they need to be taken life-long and, despite therapy, people with AIH can go on to develop liver cirrhosis, liver failure and the need for a liver transplant.
Due to inherent problems with existing treatments, new approaches are urgently needed.