Elsevier

Transplantation Proceedings

Volume 43, Issue 9, November 2011, Pages 3455-3459
Transplantation Proceedings

Organ transplantation
Attempt to Rescue Discarded Human Liver Grafts by End Ischemic Hypothermic Oxygenated Machine Perfusion

https://doi.org/10.1016/j.transproceed.2011.09.029Get rights and content

Abstract

In a porcine liver transplant model, a brief period of oxygenated hypothermic machine perfusion (HMP) at the end of simple cold storage (SCS) has been shown to improve the viability of damaged liver grafts. To test the clinical validity of this strategy, we randomized SCS-discarded human liver grafts to either 4 hours of HMP (n = 13) or an additional 4 hours of SCS (n = 14). All livers were then warm reperfused to mimic ischemia-reperfusion injury ex vivo. The settings for HMP were: portal vein: 3 mm Hg, 300 mL/min and hepatic artery: 20 mm Hg, po2: 300 mm Hg. Perfusion used Kidney Machine Perfusion Solution at 4°C to 8°C. During warm reperfusion, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) values were higher (P < .015) among the SCS versus HMP methods at all times. The AST slope was lower in HMP versus SCS (P = .01). The LDH slope tended to be lower for HMP versus SCS (P = .07). Morphological scores were not different between HMP and SCS. At the start of warm reperfusion, MAPK was lower in HMP versus SCS (P = .02). Endothelin-1 (EDN1) and ICAM-1 tended to be lower in HMP versus SCS (P = .1 and .07, respectively). No difference was noted in MAPK, EDN1, and ICAM-1 after 60 or 120 minutes of warm reperfusion. In conclusion, HMP down-regulated MAPK and tended to reduce EDN1 and ICAM-1 mRNA in human liver grafts. During warm reperfusion, HMP versus SCS livers showed reduced AST and LDH release but no morphological difference. Further optimization of liver HMP may require different timing/duration of perfusion and/or an higher perfusion temperature.

Section snippets

Human Livers

Between 2006 and 2010, we studied 27 livers that could not be allocated by Eurotransplant and were discarded for the following reasons: steatosis > 30% (n = 14), not usable DCD (n = 7), donor malignancy (n = 4), failed (re)allocation (n = 1), atheromatosis (n = 1), poor perfusion (n = 1) or rising liver function tests (n = 1) (Table 1). This protocol was approved by our ethics committee and endorsed by the Belgian Liver Intestinal Committee.

Preservation

All livers included in the study were procured

Results

Both HMP and SCS groups had similar donor characteristics as well as values of AST, alanine aminotransferase, bilirubin, and sodium. The percentages of DCD and steatotic livers were not different between HMP (36% and 55%, respectively) and SCS (58% and 36%; P = .49 and .41, respectively). Total cold ischemia time was not different between HMP (17 hours, 28 minutes ± 3 hours, 42 minutes) and SCS (15 hours, 58 minutes ± 2 hours, 47 minutes) livers (P = .27; Table 3).

During warm reperfusion, AST

Discussion

This study investigated the possibility to ameliorate cold-preserved marginal human liver grafts by subjecting them to a short 4-hour period of oxygenated HMP. In contrast with other transplant animal experiments, no clear benefits were demonstrated in our ex vivo rewarming experimental setting.12, 13, 14

During warm perfusion, concentrations of AST and LDH were lower in livers that had been machine perfused compared with those that had been cold-stored only. This observation possibly points to

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  • Challenges to liver transplantation and strategies to improve outcomes

    2015, Gastroenterology
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    In an additional study, discarded livers were randomly stored in the cold or perfused for 4 hours using the machine system (total preservation time of approximately 16 hours). The degree of reperfusion injury was tested through subsequent ex vivo perfusion of liver grafts at body temperature with diluted red blood cells for 2 hours showing reduced aspartate transaminase and lactate dehydrogenase release when compared with cold stored livers, but no morphological difference could be identified.140 Another technique of machine-mediated cold liver perfusion involves a hyperbaric oxygenated perfusate delivered through the portal vein only at low pressure 1 to 2 hours before implantation.

  • HOPE for human liver grafts obtained from donors after cardiac death

    2014, Journal of Hepatology
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    The worldwide experience in human machine liver perfusion is very scarce, and there has been no report to date on transplantation after ex situ machine perfusion of human DCD livers. Current research remains limited to ex situ perfusion of DCD livers without further implantation [38–40], or to machine perfusion of organs derived from brain death donors either by hypothermic perfusion without active oxygenation [15] or by normothermic perfusion for several hours with blood (Friend P. 15th March 2013, BBC news). The Barcelona group has been the only group up to now, who performed in situ perfusion (NECMO) and transplantation in Maastricht II donors [41].

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This research was funded with the Fund for Scientific Research Flanders (FWO) grant No. G.0577.08 and No. G.0619.09 and an unrestricted grant form Astellas and Roche, Belgium. Jacques Pirenne and Diethard Monbaliu are holders of a CAF (Belgium Central Department for Plasma Fractionation) chair for abdominal transplant surgery. Katrien Vekemans is a postdoctoral researcher of the “Fund for Scientific Research Flanders.”

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