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).