Novel approaches in optimising steatotic livers for transplantation

Thesis

Normothermic machine perfusion (NMP) has the potential to transform liver transplantation by facilitating the safe and reliable transplantation of higher-risk livers, thereby reducing the number of waiting list deaths. However, it poses logistical challenges and the evidence to support its potential beneficial effects in steatotic livers remain to be elucidated in human studies. This thesis aims to investigate whether the preservation of steatotic livers can be enhanced by NMP resulting in improved post-transplant outcomes through a reduction in ischaemia-reperfusion injury (IRI) and by reducing the amount of intra-hepatic fat. I have demonstrated that static cold storage (SCS) prior to NMP is safe and feasible with comparable clinical outcomes and markers of graft injury to those in continuous NMP and significantly improved compared to SCS. This is likely to facilitate clinical adoption by improving logistics and reducing the cost. I have provided evidence to support NMP’s role in steatotic liver transplantation where early biochemical function is improved compared to cold stored steatotic livers. Furthermore, IRI characterised histologically and systemically is attenuated in steatotic NMP compared to SCS livers. Finally, I have demonstrated that in conjunction with de-fatting adjuncts, the ex situ function of steatotic livers can be improved and the amount of fat within the liver can be reduced by 45%. This is achieved through altering liver fat metabolism to favour improved/enhanced fatty acid oxidation with a concomitant reduction in de novo lipogenesis.

Authors: Ceresa, C

• DOI: 10.5287/ora-exkvmvm0y
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English