Optimisation of steatotic donor livers in the era of machine perfusion
Research type
Research Study
Full title
High-risk steatotic donor livers in the era of normothermic machine perfusion: Application of novels therapies to achieve transplantability criteria
IRAS ID
280477
Contact name
Peter Friend
Contact email
Sponsor organisation
University of Oxford / Clinical Trials and Research Governance
Duration of Study in the UK
2 years, 4 months, 1 days
Research summary
A third of donated livers cannot be used for transplants due to the presence of fat within the liver cells (known as non-alcoholic fatty liver disease, NAFLD). Transplanting a fatty liver carries a greater risk to the patient compared to a normal liver as these livers do not tolerate conventional ice-box storage before transplantation.
Our preliminary experiments point to an innovative defatting strategy for treatment of fatty human livers that were declined for transplantation. These livers were preserved on a machine in very similar conditions to those in the body (termed normothermic preservation). We added a combination of currently available drugs to release fat from liver cells, and we then removed the fat using a filter. This reduced the amount of fat in the liver and improved its function.
However, evidence suggests that other key pathways may further enhance the success of these defatting strategies, in particular, pathways associated with oxygen sensing that are regulated by hypoxia inducible factors (HIFs). HIFs are activated in low oxygen environments and have both a protective and deleterious effect in the progression of NAFLD. Evidence from pre-clinical experiments suggests that HIF expression can be selectively modulated using pharmacological agents thereby providing therapeutic targets for NAFLD.
We will initially investigate the effect of the defatting strategies on HIF expression within the liver using samples from our preliminary study. This will inform the basis our main study where we anticipate that the selective pharmacological modulation of HIF pathway during normothermic liver preservation will improve functional outcomes.
REC name
London - Riverside Research Ethics Committee
REC reference
20/PR/0111
Date of REC Opinion
2 Jul 2020
REC opinion
Favourable Opinion