Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion

Abstract

There continues to be significant debate regarding the most effective mode of ex situ machine perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic machine perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic machine perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with machine perfusion may require the optimization of redox status through repletion or supplementation of reducing agents.

Keywords

• steatosis
• subnormothermic
• normothermic
• machine perfusion
• anti-oxidant
• metabolomics
• liver transplantation