Altered portal flow in cirrhotic livers
Both cirrhotic (n=7, characteristics Table 1) and non-cirrhotic (n=4, characteristics Table 1) livers had a stable arterial flow with minimal variation during perfusion (235 ml/min (IQR:214.7-249) in cirrhotic livers vs. 230 mL/min (IQR:21.3-239.5) in non-cirrhotic livers, Figure 1A). A significant lower portal flow in cirrhotic livers was observed compared to non-cirrhotic livers (523 mL/min (IQR:489-557) vs 1678 mL/min (IQR:1596-1710)), respectively, p<0.001 (Figure 1B). Arterial resistance remained stable and did not significantly differ between the cirrhotic and non-cirrhotic livers (p=0.115) (Fig 1C) whereas the portal resistance of the cirrhotic livers proved to be higher over the entire perfusion time compared to non-cirrhotic livers (p<0.001) (Fig 1D). All livers produced bile during perfusion, but significantly more bile was produced by the cirrhotic livers (55 mL (IQR:37-61) vs 28 mL (IQR:22-60)) (p=0.034) (Figure 1E).
Explanted livers showed good viability during perfusion
As markers of hepatocellular injury, release of ALT and AST into the perfusate was measured throughout the perfusion and results are presented in figure 2 A and B. Levels of ALT and AST levels were significantly higher in the non-cirrhotic livers compared to the cirrhotic livers. Figure 2C-F demonstrates the liver function parameters measured in perfusate. Lactate clearance was observed after 30 min of perfusion in the non-cirrhotic liver group and lactate levels remained low (1.39 mmol/L (IQR:0.48-.29)) while cirrhotic livers showed higher levels of perfusate lactate (13.25 mmol/L (IQR:3.20-22.91) after 360 min of NMP). A correlation between perfusate lactate levels (lactate AUC) and the MELD score of the patients (R2=0.793) was observed. All livers were able to maintain albumin perfusate levels within physiological serum levels. Perfusate total bilirubin levels were significantly higher in cirrhotic livers compared to non-cirrhotic livers (29.63 µmol/L (IQR:22.37-34.81) vs 10.30 µmol/L (IQR:9.67-14.27) respectively, p=0.026). Viability markers as measured in bile (figure 2G-J) demonstrated good cholangiocyte viability in all livers with a biliary pH >7.6, high bicarbonate excretion and stable bilirubin excretion into bile. Glucose resorption function was better preserved in cirrhotic livers (Δ glucose <10 mmol/L) than in non-cirrhotic livers, meeting the defined viability criteria (see method section).