*Purpose: Despite increasing use of machine perfusion as an organ preservation and rescue technique in liver transplantation, significant organ shortages and waitlist mortality highlight a continuing need for improved organ recovery methods. We have previously described a platform for ex vivo support of explanted porcine livers using cross-circulation. Here, we describe the use of xenogeneic cross-circulation (XCC) for the support of explanted human livers for 24 hours.

*Methods: Human donor livers (n = 2) declined for clinical transplantation were procured and placed on normothermic, veno-arteriovenous XCC with anesthetized, immunosuppressed, complement depleted porcine hosts (Fig. 1). Longitudinal analyses of extracorporeal livers and porcine hosts were performed over 24 hours of XCC.

*Results: Throughout 24 hours of support, extracorporeal livers maintained gross architecture, normothermic perfusion, and biliary integrity (Fig. 2A-C). Functionally, the liver demonstrated stable or improved oxygen consumption, lactate clearance, protein metabolism, and alkaline bile composition (Fig. 2D-G). Liver enzymes increased upon reperfusion, but decreased or remained stable throughout cross-circulation (Fig. 2H, I). Organ weight remained stable and fibrinolytic markers improved over the course of support (Fig. 2J-K). There was no major histologic evidence of hepatocellular injury (Fig. 2L). Circuit parameters remained physiologic during XCC (hepatic artery flow 233 ± 55 mL/min; hepatic artery pressure 89 ± 45 mmHg; portal venous flow 510 ± 120 mL/min; portal venous pressure 10 ± 3 mmHg; portal venous O₂ saturation 64 ± 15%).

*Conclusions: We demonstrate that XCC enables the physiologic support of explanted human livers for 24 hours. XCC has potential application as a translational research platform and clinical biotechnology for organ salvage and recovery.

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