Simultaneous quantification of native human and transgenic porcine liver function in a decedent model of extracorporeal cross-circulation.
Shaked A., McRae MP., Imperial JC., Lanieri L., Sagar A., Olthoff KM., Low S., Swenson KG., Friend P., Everson GT.
Porcine livers have the potential to support liver function via extracorporeal liver cross-circulation (ELC) until recovery or transplantation. To assess the functional integrity of both native human and porcine livers during ELC, we used the clearance of intravenously administered 13C-cholate to probe effective hepatic perfusion in four decedents maintained on ELC for 72-102 hours. Genetically modified porcine livers (EGEN-5784) were perfused using the OrganOx metra-ELC device. Hepatic filtration rate (HFR) was calculated for the native human liver and the EGEN-5784 liver in ELC. During ELC, total HFR increased substantially compared to pre-ELC values, exceeded the upper limit of the normal range, and remained stable throughout the ELC period. Simultaneous measurement of cholate clearance in human and porcine livers during ELC provides real-time assessment of each organ's functional contribution and may inform decisions regarding optimal ELC duration, timing of disconnection, and necessity of liver transplantation.