Customized normothermic machine perfusion decreases ischemia–reperfusion injury compared with static cold storage in a porcine model of liver transplantation

Abstract

Background Liver transplantation has been demonstrated to be the best treatment for several liver diseases, while grafts are limited. This has caused an increase in waiting lists, making it necessary to find ways to expand the number of organs available for transplantation. Normothermic perfusion (NMP) of liver grafts has been established as an alternative to static cold storage (SCS), but only a small number of perfusion machines are commercially available. Methods Using a customized ex situ machine perfusion, we compared the results between ex situ NMP and SCS preservation in a porcine liver transplant model. Results During NMP, lactate concentrations were 80% lower after the 3‐h perfusion period, compared with SCS. Bile production had a 2.5‐fold increase during the NMP period. After transplantation, aspartate transaminase (AST) and alanine transaminase (ALT) levels were 35% less in the NMP group, compared to the SCS group. In pathologic analyses of grafts after transplant, tissue oxidation did not change between groups, but the ischemia–reperfusion injury score was lower in the NMP group. Conclusion NMP reduced hepatocellular damage and ischemia–reperfusion injury when compared to SCS using a customized perfusion machine. This could be an alternative for low‐income countries to include machine perfusion in their therapeutic options.

Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs

“…Despite the activation of liver tissue, the number of proinflammatory molecules immediately released into the recipient’s circulation is lower compared to SCS grafts with a subsequent reduction of systemic inflammation in the recipient 40 . The observed impact on immediate clinical outcome parameters is the direct consequence, including less systemic hypoperfusion and renal-protective effect compared to its SCS counterpart 41–43 . NMP is also known to reduce cytokine concentration in the transplanted graft and reduce inflammatory mediators, both due to transcriptional changes and the mechanical act of flushing these cytokines into the perfusate, which is then discarded 44 .…”

“…40 The observed impact on immediate clinical outcome parameters is the direct consequence, including less systemic hypoperfusion and renal-protective effect compared to its SCS counterpart. [41][42][43] NMP is also known to reduce cytokine concentration in the transplanted graft and reduce inflammatory mediators, both due to transcriptional changes and the mechanical act of flushing these cytokines into the perfusate, which is then discarded. 44 It is thus reasonable to think that our findings of reduction in renal complications and less serious bleeding events may result from a reduction in early systemic inflammation with NMP.…”