The development of long-term normothermic machine perfusion in liver transplantation: assessment of organ quality and viability, and an exploration of barriers to clinical practice

Abstract

Various machine perfusion techniques utilised in liver transplantation have established advantages when applied clinically in the short term. However, if perfusion could be safely extended beyond hours, to days or even weeks under normothermic and physiologic conditions, the opportunity presents itself for more sophisticated resuscitation, assessment and repair of these organs. Challenges to safely perfusing human livers for this duration are not insignificant – particularly as metabolic waste will accumulate within the perfusion circuit, nutrients for metabolic needs will be required, and the monitoring and resourcing for continued perfusion would be mandated. If successful, however, the potential for not just resuscitation and viability assessment, but the introduction of therapeutic intervention to further improve graft quality (eg stem cell therapy, de-fatting therapy) has the potential to dramatically increase the number of livers available for transplantation. This thesis presents the current state of evidence for viability assessment of marginal grafts using normothermic machine perfusion, as well as a description of the establishment and subsequent validation of a long-term normothermic perfusion platform in a pre-clinical setting.