The Optimisation of Human Steatotic Livers for Transplantation
Research type
Research Study
Full title
Exploring the structural and functional effects of normothermic machine perfusion and de-fatting agents on human steatotic livers
IRAS ID
195301
Contact name
Peter Friend
Sponsor organisation
University of Oxford
Duration of Study in the UK
2 years, 4 months, 1 days
Research summary
Liver transplantation is a successful treatment for end-stage liver disease but is limited by donor organ availability. It is therefore of great importance to increase the donor pool. Fatty livers derive poor outcomes when transplanted and as a result, a large number are discarded. Obesity levels in the UK and worldwide are increasing at an alarming rate. With this, comes an increasing incidence of fatty liver disease. An increase of fatty livers in the donor pool is therefore inevitable and identifying methods of optimising and salvaging these livers for transplantation is essential.
The key to successful transplantation of fatty livers may lie in organ preservation. New technology involves maintaining the liver on a machine that provides oxygen and nutrition at normal body temperature, known as normothermic machine perfusion (NMP). We believe that NMP will allow the safe transplantation of fatty livers by: 1) avoiding the deleterious effects of cooling; and, 2) enabling the delivery of de-fatting agents to remove the fat from the liver before transplantation.
Livers which have been discarded due to a high-fat content will be obtained. Tissue samples will be collected and de-fatting agents will be validated and refined for human cells in a laboratory setting. Once the agents have been optimised, they will be applied to whole livers through the NMP circuit. By examining biopsy and perfusate samples from the circuit for fat content it will be possible to establish the effect on NMP +/- de-fatting agents on fatty livers. It is hoped to understand the process by which de-fatting occurs by investigating key processes of fat breakdown in the liver.
The combination of NMP and de-fatting agents might allow the safe and reliable transplantation of fatty livers. This couldl result in more livers being transplanted and ultimately, lives saved.REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
16/NE/0248
Date of REC Opinion
12 Jul 2016
REC opinion
Favourable Opinion