The perfused liver utilisation study (PLUS): challenges and innovation in the evaluation of an emerging technology.

Previous studies suggest that donor liver normothermic machine perfusion (NMP) reduces injury and enables functional assessment, resulting in an increase in utilisation. The PLUS study was designed to assess the impact of NMP availability on utilisation of livers at high risk of non-use. Using a threshold-crossing design, functional utilisation was assessed in a real-world retrospective registry-based control cohort. A predetermined efficacy threshold was set, and a prospective cohort was recruited in all UK liver transplant centres with NMP made available for all livers at high risk of non-utilisation. Availability of NMP resulted in a significant increase in functional utilisation (OR: 1.26, 95% CI: 1.04-1.53), but this did not exceed the pre-determined efficacy threshold. The threshold was exceeded in the subgroup of donation after circulatory death (DCD) livers, although this increase was reduced with adjustment for the use of normothermic regional perfusion. NMP was used in only 31% of retrieved livers, with variation between centres. The benefit of having NMP available was less than anticipated, likely due to low use in some centres associated with staff availability. Provision of NMP as a service, or centralisation of NMP use in assessment and recovery centres, may improve uptake.