Purpose. An urgent need for more liver grafts for transplantation has prompted the use of more suboptimal organs. Particularly in these more marginal livers adequate assessment of function is required.We present a novel model of ex vivo human liver reperfusion, which allows for accurate simulation of clinical reperfusion and offers a valuable tool for assessing function during ex vivo reperfusion.

Methods. Four human DCD livers, declined for transplantation were cold-stored for 7 h and then reperfused ex vivo with diluted whole blood at 37[deg]C for 3 hours using a commercial perfusion device. Throughout, perfusion parameters were recorded and tissue was sampled and analyzed by LC/MS for energy-related metabolites. In parallel, sequential tissue biopsies were collected during clinical liver transplantations (n=19) and similar analysis was performed during reperfusion.

Results. All ex vivo reperfused livers demonstrated clear metabolic function, including the sustained production of bile, uptake of oxygen and reconstitution of energy charge ((ATP+1/2ADP)/(ATP+ADP+AMP))(Fig. 1). Representative injury was sustained, evidenced by release of ALT, CRP and inflammatory cytokines. Similarly, in clinical liver transplantation, energy charge was reconstituted in varying degrees between livers (Fig. 2). Energy charge after reperfusion was found to significantly correlate to early allograft dysfunction in this group (P<0.05).

Conclusion. This novel simulation of ex vivo liver reperfusion is representative of energy recovery in clinical liver transplantation and offers a valuable tool for assessing ex vivo preservation. Moreover, energy status was identified as a potential predictor of transplant outcome clinically.

CITATION INFORMATION: Bruinsma B, Avruch J, Sridharan G, Weeder P, Karimian N, Markmann J, Uygun K, Yeh H. Metabolic Recovery and Ex Vivo Simulation of Early Liver Reperfusion. Am J Transplant. 2016;16 (suppl 3).

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