Hepatic Steatosis and Normothermic Perfusion—Preliminary Experiments in a Porcine Model

Abstract

Steatotic livers are increasingly common in the donor population. Cold storage of steatotic livers exacerbates ischemia-reperfuson injury and risks primary nonfunction and recipient death. Normothermic preservation avoids prolonged cooling of the organ and may be well suited to the preservation and resuscitation of damaged livers. By ex vivo normothermic perfusion, it may be possible to preserve and improve steatotic livers, so that transplantation is a viable option. In a porcine model, streptozotocin was used to induce a hyperglycemic, ketotic state that, together with a high fat diet, resulted in mild hepatic steatosis at 5 weeks. A blood-based oxygenated ex vivo normothermic preservation system was then used to compare extended preservation of normal and mildly steatotic porcine livers at physiological pressures and flows. Serial liver biopsies were stained with Oil Red O, a specialist triglyceride stain, and were analyzed using custom-designed image analysis to quantify the degree of lipid deposition. Steatotic livers were capable of correcting the perfusate base excess and maintaining factor V and bile production and showed markers of liver injury comparable with normal livers. Steatotic livers had a significantly higher urea production and required no glucose support. Preliminary results suggest that prolonged normothermic perfusion results in a reduction in steatosis. This study suggests that steatotic livers can be successfully preserved using normothermic preservation for prolonged periods and that normothermic preservation facilitates a reduction in hepatic steatosis. Further studies are now needed including transplantation of steatotic livers after normothermic preservation.