Metabolic balance of human livers during long-term normothermic machine perfusion

Normothermic machine perfusion (NMP) is used to preserve and assess the viability of (extended criteria) high-risk donor livers. Long-term NMP (LT-NMP; ≥24 h) is emerging as a method to improve or repair livers initially deemed unsuitable for transplantation. This study investigated metabolism during LT-NMP, focusing on hepatic energy consumption and nitrogen and electrolyte balances to better understand long-term perfusion requirements. In this study, we measured oxygen consumption (V^_ O₂) and carbon dioxide production (V^_ CO₂) to determine the energy expenditure of 14 human livers during LT-NMP for 7 days. In addition, hepatic balances of glucose and lactate as well as of nitrogen and electrolytes were determined. Initial high metabolic rates during the first day of LT-NMP decreased and stabilized at nearly 50% on day 3, suggesting a quiescent state until day 7. Most energy was derived from glucose (75%–88%). Continuous amino acid supplementation was essential to maintain an anabolic state, whereas livers without supplementation became catabolic. Although net electrolyte balances were close to zero, significant uptake and release of electrolytes occurred throughout LT-NMP. During LT-NMP, livers reached a metabolically quiescent state after 3 days with decreased energy consumption. Tailoring perfusate composition and supplementation protocols to the specific needs of the liver could enhance organ preservation and potentially expand the pool of viable donor livers after LT-NMP.