Subnormothermic Machine Perfusion for Ex Vivo Preservation and Recovery of the Human Liver for Transplantation

Abstract

To reduce widespread shortages, attempts are made to use more marginal livers for transplantation. Many of these grafts are discarded for fear of inferior survival rates or biliary complications. Recent advances in organ preservation have shown that ex vivo subnormothermic machine perfusion has the potential to improve preservation and recover marginal livers pre- transplantation. To determine the feasibility in human livers, we assessed the effect of 3 hours of oxygenated subnormothermic machine perfusion (21 °C) on seven livers discarded for transplantation. Biochemical and microscopic assessment revealed minimal injury sustained during perfusion. Improved oxygen uptake (1.30 [1.11–1.94] to 6.74 [4.15–8.16] mL O2/min.kg liver), lactate levels (4.04 [3.70–6.00] to 2.29 [1.20–3.42] mmol/L) and adenosine triphosphate content (45.0 [70.6–87.5] pre-perfusion to 167.5 [151.5–237.2] pmol/mg after perfusion) were observed. Liver function, reflected by urea, albumin and bile production was seen during perfusion. Bile production increased and the composition of bile (bile salts/phospholipid ratio, pH and bicarbonate concentration) became more favorable. In conclusion, ex vivo subnormothermic machine perfusion effectively maintains liver function with minimal injury and sustains or improves various hepatobiliary parameters post-ischemia.

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

“…5,6 Although recent data from animal models and (discarded) human donor livers have provided promising results suggesting that endischemic MP has relevant protective effects on the bile ducts of donation after cardiac death (DCD) liver grafts, the most optimal perfusion temperature during end-ischemic MP has not been investigated. [7][8][9][10][11][12][13][14][15][16][17] The aim of this study was, therefore, to assess the optimal perfusion temperature during end-ischemic oxygenated MP for protection of the large bile ducts against I/R injury in a DCD rat liver model.…”

Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

“…These findings were extended to a feasibility study using discarded human livers, in which SNMP at 21°C effectively preserved liver function during the preservation period (102). The latter was reflected by an increase in hepatic ATP, urea and albumin levels throughout the SNMP procedure as well as by the histological profiles before and after the perfusion period (102). Clinical studies on SNMP are currently lacking, and future investigations could provide additional insight into the potential benefits of SNMP over other perfusion techniques.…”

Functional Human Liver Preservation and Recovery by Means of Subnormothermic Machine Perfusion

“…Subnormothermic machine perfusion offers a viable alternative to conventional cold storage, as well as hypothermic and normothermic machine perfusion modalities. Various different systems exist; all offer different advantages and disadvantages 3,9,20 . SNMP allows for perfusion without an oxygen carrier, as metabolic oxygen demands at 21 °C are met by active oxygenation of the perfusate.…”

“…Directly observable parameters such as bile production and oxygen uptake are real time measurements that can be used to assess the liver pre-transplantation. Similarly, markers of cellular injury and ischemia (K+, lactate release) can be measured directly in the perfusion solution and may be indicative of organ function 20 . As machine perfusion technology develops further and achieves more widespread clinical application, accurate correlations between ex vivo function and clinical outcome can be made and perfusion parameters will be useful in aiding decisions to transplant or reject marginal-quality livers.…”

“…Standard liver procurement technique involves in situ arterial flush of the liver following aortic cross-clamping in brain dead donors (DBD) or after circulatory arrest in circulatory death donors (DCD), described in more detail elsewhere 20 . Additionally, the liver is cooled during the procurement by filling the donor's abdominal cavity with ice.…”