Assessment of Ex Situ Liver Function by Indocyanine Green Clearance During Clinical Normothermic Machine Perfusion of Extended Criteria Grafts

Normothermic machine perfusion (NMP) enables pretransplantation assessment of donor liver viability to increase donor liver utilization. However, unambiguous objective criteria to determine integrated liver function during NMP to decide upon acceptance are still lacking. This study investigates whether the indocyanine green (ICG) elimination test can be applied to assess liver function during NMP. Donor livers underwent dual-hypothermic oxygenated machine perfusion and NMP. The ICG elimination test was improved during an optimization phase (n = 10) and tested against current functional perfusion parameters and posttransplantation outcomes in clinically perfused livers (n = 32). The ICG plasma disappearance rate (PDR) during NMP was dependent on perfusion blood flow and liver weight. The corrected PDR (NMP-PDR) was correlated to the hepatic extraction rate (R = 0.923; P > 0.001) and ATP content in liver biopsies at 2 h of NMP (R = 0.692; P = 0.027). In the clinical phase, the length of the functional warm ischemia time in the donation process was inversely correlated to the NMP-PDR (P = 0.042). Both individual acceptance criteria (lactate clearance, ability of self-regulate pH, Δbicarbonate, and ΔpH) and overall hepatocellular and cholangiocellular acceptance criteria were correlated to the NMP-PDR. The NMP-PDR was higher in the cohort accepted for transplantation (n = 18; 18.1%/L·kg [14.0% to 22.7%/L·kg]) than in the nontransplanted cohort (n = 14; 11.8%/L·kg [8.8% to 12.9%/L·kg]; P < 0.0001). Furthermore, the NMP-PDR correlated with the liver graft assessment following transplantation at 7 d score posttransplantation (R = -0.551; P = 0.027). We demonstrate that the NMP-PDR correlates with both liver function during NMP and short-term posttransplantation outcomes. This simple objective test has the potential to increase donor liver utilization rate, while preventing hepatocellular dysfunction posttransplantation.