A multi-centre prospective study of donor-specific antibodies in children following liver transplantation
Dr Girish Gupte of Birmingham Children’s Hospital discusses his research and what it means for the future of treating childhood liver disease.
What is this study looking at?
Liver transplant is a life-saving option for children with end stage liver disease. Although associated with excellent long-term outcomes, it has been recognised that donor liver damage can occur in 60% of patients, whilst liver function tests can be normal. The exact cause of the damage to the transplanted liver is not known.
Rejection (the body’s immune system attacking the new liver) can be of two types. One type is cellular, caused by T lymphocytes and methods of diagnosis are well established. The other is antibody mediated (provoked) rejection caused by donor specific antibodies (DSA). In other solid organ transplants (e.g. kidney and heart), antibody mediated rejection is known to cause long-term damage to donor liver needing re-transplantation. Recently, donor specific antibodies have been identified in the liver transplant population. It is not clear if donor specific antibodies are formed as a result of donor liver damage or if they are the main cause of antibody-mediated rejection leading to liver damage.
This study is being carried out with collaboration between all three specialist paediatric liver units. The blood tests necessary for detecting antibodies will be drawn at the time of routine follow-up and other blood tests involved in the clinical care of the patient.
Why is this research important?
This study will aim to fill the gaps in knowledge by:
– investigating the exact time of DSA development
– investigating its specific contribution to rejection i.e. are the donor specific antibodies a cause of rejection or a consequence of it?
– identifying the trend of DSA levels after transplant to understand more about the behaviour of these antibodies. Blood tests at present cannot be requested routinely at several points in the posttransplant follow-up, partly due to cost.
– estimating prevalence (how widespread) and incidence (risk of it occurring) of DSA mediated rejection
What about the future?
The estimated end date of the study is 2023. This study has the potential to improve outcomes following liver transplantation by being able to diagnose the type of rejection more accurately and therefore treat appropriately. This will hopefully lead to an increase in the lifetime of the transplanted liver.