Predictor parameters of liver viability during porcine normothermic ex situ liver perfusion in a model of liver transplantation with marginal grafts

Abstract

Normothermic ex situ liver perfusion (NEsLP) offers the opportunity to assess biomarkers of graft function and injury. We investigated NEsLP parameters (biomarkers and markers) for the assessment of liver viability in a porcine transplantation model. Grafts from heart‐beating donors (HBD), and from donors with 30 minutes (donation after cardiac death [DCD]30′), 70 minutes (DCD70′), and 120 minutes (DCD120′) of warm ischemia were studied. The HBD, DCD30′, and DCD70′‐groups had 100% survival. In contrast, 70% developed primary nonfunction (PNF) and died in the DCD120′‐group. Hepatocellular function during NEsLP showed low lactate (≤1.1 mmol/L) in all the groups except the DCD120′‐group (>2 mmol/L) at 4 hours of perfusion (P = .04). The fold‐urea increase was significantly lower in the DCD120′‐group (≤0.4) compared to the other groups (≥0.65) (P = .01). As for cholangiocyte function, bile/perfusate glucose ratio was significantly lower (<0.6) in all the groups except the DCD120′‐group (≥0.9) after 3 hours of perfusion (<0.01). Bile/perfusate Na+ ratio was significantly higher (≥1.2) after 3 hours of perfusion in all the groups except for the DCD120′‐group (≤1) (P < .01). Three hours after transplantation, the DCD120′‐group had a significantly higher international normalized ratio (>5) compared to the rest of the groups (≤1.9) (P = .02). Rocuronium levels were higher at all the time‐points in the animals that developed PNF during NEsLP and after transplantation. This study demonstrates that biomarkers and markers of hepatocellular and cholangiocyte function during NEsLP correlate with the degree of ischemic injury and posttransplant function.

An integrated perfusion machine preserves injured human livers for 1 week

“…5, we summarize our current understanding of how to best assess liver function and viability during ex vivo perfusion. Besides the conventional parameters (that is, lactate clearance, perfusate pH and bile production) as previously proposed 4,[34][35][36] , we rely on the response to glycolytic hormones, vasoactive drugs and on clearance of ammonia, as well as histology and ATP synthesis.…”

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

“…(51,52) In a porcine LT model, it was shown that a lower bile/perfusate glucose ratio (<0.6) and a higher bile/ perfusate sodium ratio (≥1.2) during NMP was observed in DBD donors or donors with short warm ischemia (up to 70 minutes) compared with donors with long warm ischemia (120 minutes). (13) Bile composition of rat livers assessed during NMP also Gaurav et al (12) Na and bile glucose-blood glucose Blood gas -/100 NAS Linares-Cervantes et al (13) Bile/perfusate glucose ratio Blood gas 20/-Bile duct viability Bile/perfusate Na ratio Blood gas Matton et al (2) Bicarbonate, pH, and glucose Blood gas -/23 Bile duct injury/NAS Bile/perfusate ratio Blood gas Sutton et al (14) Bilirubin and bicarbonate Blood gas -/12 Bile duct viability de Vries et al (15) pH Blood gas -/7 Bile duct viability Afford et al (16) * pH Unknown 31/-ITBL Habib et al (17) Bile (10) Choleretic activity HPLC -/35 PGD CA/CDCA ratio HPLC Xu et al (21) Bile salts, phospholipids, and cholesterol Spectrophotometry, ELISA 18/-Graft function Ko et al (22) Phospholipids HPLC -/17 Graft function Baumgartner et al (23) Bile acids, phospholipids, and cholesterol Not known -/12 Early graft dysfunction Sánchez-Bueno et al (24) Bile acids, phospholipids, and cholesterol Spectrophotometry -/25 ACR/PNF Chan et al (25) Bile salts ELISA 16/-Early graft dysfunction…”

Biomarkers of Liver Injury during Transplantation in an Era of Machine Perfusion

“…As alluded to above, the development of ischaemic cholangiopathy is a risk in livers from DCD donors, and many teams have investigated biomarkers of biliary function during NMP. In a study by Linares-Cervantes et al, the authors suggested that a bile to perfusate glucose ratio <0.6717 and a bile glucose level <15 mmol/L resulted in 0% incidence of ischaemic cholangiopathy, at long-term follow-up [49]. In addition, this study found 2 new biomarkers (urea and bile Na + ) to assess hepatocellular and cholangiocyte viability [52].…”

“…Linares-Cervantes et al described four biomarkers in an NMP setting relating to biliary and hepatocellular viability in an experimental model with different degrees of ischaemia [49]. The authors concluded that a lactate level <2 mmol/L at 4 h of perfusion, increase in urea level ≥0.5-fold, bile/perfusate glucose ratio ≤0.7 and bile/perfusate Na+ ratio ≥1.1 within 4 h of perfusion, strongly correlated with successful liver transplantation after NMP.…”