Immunological response to normothermic machine perfusion of the liver
Research type
Research Study
Full title
Normothermic machine perfusion of marginal liver allogfrafts. Does this create a immuno-reactive microenvironment?
IRAS ID
281445
Contact name
Thamara Perera
Contact email
Sponsor organisation
Research and development department
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Significant improvements in morbidity and mortality have occurred since the inception of liver transplantation in the 1960’s. However, the prevention and management of immune mediated graft rejection presents a significant challenge to clinicians. Rejection occurs because the recipient’s immune system detects the foreign proteins, known as antigens, on the implanted liver and responds in a manner that aims to destroy and contain these foreign cells. The demand for donor livers currently exceeds the supply and approximately 11% of patients on the liver transplant waiting list die before a graft becomes available. Therefore, donor livers are a precious commodity and all measures should be taken to avoid the unnecessary loss of grafts to the process of rejection.
Normothermic machine perfusion (NMP) is a method of preserving the donor organs between removal from the donor and insertion into the recipient. This device delivers oxygenated blood at normal body temperature and allows the liver to continue its normal metabolic functions. However, it is unclear how the immune cells that are present in the liver respond to this period of ex-situ perfusion. Our hypothesis is that the immune cells present in the donor liver increase their activity and their secretion of proinflammatory chemicals during NMP. This may result in earlier and more severe episodes of rejection in comparison to the standard method of ice box preservation. Our study aims to assess the cellular microenvironment of the liver whilst it is undergoing NMP by taking liver biopsies and blood samples from the liver and perfusion circuit respectively. These results will be compared to a control sample from grafts that undergo the standard preservation method, static cold storage. A thorough understanding of the changes that occur may lead to interventions that aim to mitigate this response whilst on NMP and/or influence the post-operative management of immunosuppressive medications.
REC name
Wales REC 7
REC reference
21/WA/0300
Date of REC Opinion
27 Sep 2021
REC opinion
Favourable Opinion