Abudhaise, Hamid; (2021) Investigation of hypothermic machine perfusion of human donor livers for improved organ preservation: measurements of organ quality and safety. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Introduction Hypothermic machine perfusion (HMP) could improve the outcome of marginal liver transplantation, but the optimal perfusion setup and injury markers are unknown. The null hypothesis herein is no difference in cellular and mitochondrial injury during ex-situ preservation when comparing SCS and end-ischaemic HMP. Methods This is a single-centre, randomised study of end-ischaemic HMP in discarded human livers. A total of 45 livers were preserved for 4 hours with static cold storage (n = 7), arterial perfusion (n = 10), non-oxygen supplemented venous perfusion (n = 17), and oxygen supplemented venous perfusion (n = 11). Dynamic, biochemical, morphological, and mitochondrial parameters were analysed. Additionally, oxygenation kinetics and steatosis assessment were examined. Results Arterial perfusion resulted in higher resistance and lower flow compared with venous perfusion (p ≤ 0.01), as well as higher perfusate transaminases in the former group (p > 0.05). High-risk marginal livers were associated with 2-fold higher perfusate transaminases (p > 0.05) and higher post-preservation mitochondrial complex II-III activity (p = 0.01) compared to low-risk livers. Morphology and mitochondrial function were maintained in all groups and oxygenation did not trigger oxidative injury. Parenchymal oxygen measurement indicated evidence of oxygen consumption. A revised steatosis grading system using digital image analysis was accurate and showed high agreement with standard H&E assessment. Conclusion There was not enough evidence to reject the null hypothesis. Arterial-only perfusion might be inadequate for liver preservation based on the limited perfusate supply, but randomised trials are needed to determine the requirement of arterial perfusion in dual-vessel perfusion machines. The sensitivity of highrisk livers to ischaemia reperfusion injury might be reflected in their mitochondrial function, which needs to be assessed in future. Perfusate oxygenation is safe but the optimal perfusate oxygen remains unknown. DIA is a promising method, which can standardise steatosis evaluation.

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