BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Mohamed Bejaoui; Eirini Pantazi; Emma Folch-Puy; Pedro M Baptista; Agustín García-Gil; René Adam; Joan Roselló-Catafau Journal: World J Gastroenterol Date: 2015-01-14 Impact factor: 5.742
Authors: Nir I Nativ; Alvin I Chen; Gabriel Yarmush; Scot D Henry; Jay H Lefkowitch; Kenneth M Klein; Timothy J Maguire; Rene Schloss; James V Guarrera; Francois Berthiaume; Martin L Yarmush Journal: Liver Transpl Date: 2013-12-12 Impact factor: 5.799
Authors: N I Nativ; T J Maguire; G Yarmush; D L Brasaemle; S D Henry; J V Guarrera; F Berthiaume; M L Yarmush Journal: Am J Transplant Date: 2012-10-11 Impact factor: 8.086
Authors: Ricardo C Gehrau; Valeria R Mas; Catherine I Dumur; Jihee L Suh; Ashish K Sharma; Helen P Cathro; Daniel G Maluf Journal: Transplantation Date: 2015-12 Impact factor: 4.939
Authors: Nir I Nativ; Gabriel Yarmush; Alvin Chen; David Dong; Scot D Henry; James V Guarrera; Kenneth M Klein; Tim Maguire; Rene Schloss; Francois Berthiaume; Martin L Yarmush Journal: J Hepatol Date: 2013-07-19 Impact factor: 25.083