Defatting of Human Livers during Long-Term ex situ Normothermic Perfusion. Novel Strategy to Rescue Discarded Organs for Transplantation

Abstract

Objective: To develop a protocol for the defatting of steatotic liver grafts during long-term ex situ normothermic machine perfusion. Background: Despite the alarming increase in donor organ shortage, the highly prevalent fatty liver grafts are often discarded due to the risk of primary non-function. Effective strategies preventing such outcome are currently lacking. An exciting new avenue is the introduction of ex situ normothermic machine perfusion (NMP), enabling a liver to remain fully functional for up to two weeks and providing a unique window of opportunity for defatting prior to transplantation. Methods: Over a 5-year period, 23 discarded liver grafts and 28 partial livers from our resection program were tested during ex situ NMP. The steatosis degree was determined on serial biopsies by expert pathologists, and triglyceride contents measured simultaneously. Results: Of 51 liver grafts, 20 were steatotic, with up to 85% macrovesicular steatosis, and were perfused for up to 12 days. 10 livers displayed marked (5 of which almost complete) loss of fat, while the other 10 did not respond to long-term perfusion. Successful defatting was related to prolonged perfusion, automated glucose control, circadian nutrition, and L-carnitine/fenofibrate supplementation. Pseudopeliotic steatosis and the associated activation of Kupffer/stellate cells were unexpected processes that might contribute to defatting. Synthetic and metabolic function remained preserved for most grafts until perfusion end. Conclusion: Ex situ long-term perfusion effectively reduces steatosis while preserving organ viability and may in the future allow transplantation of primarily unusable high-risk grafts, significantly increasing the number of organs available for transplantation.

Steatotic Donor Transplant Livers: Preservation Strategies to Mitigate against Ischaemia-Reperfusion Injury

“…Further research on discarded steatotic human livers has been explored by Da Silva et al [183] who have recently published on defatting ex situ over multi-day perfusions. In this study, a total of 51 liver grafts were included (23 discarded liver grafts and 28 partial livers obtained hepatic resections) and were subjected to NMP.…”