Improvement of steatotic rat liver function with a defatting cocktail during ex situ normothermic machine perfusion is not directly related to liver fat content.

Siavash Raigani,Ivy Rosales,Heidi Yeh,Martin Yarmush,Cailah Carroll,Korkut Uygun,Rafic Beydoun,Hany Deirawan,Casie Pendexter,Stephanie Griffith,Pavel Strnad

doi:10.1371/journal.pone.0232886

Abstract

There is a significant organ shortage in the field of liver transplantation, partly due to a high discard rate of steatotic livers from donors. These organs are known to function poorly if transplanted but make up a significant portion of the available pool of donated livers. This study demonstrates the ability to improve the function of steatotic rat livers using a combination of ex situ machine perfusion and a “defatting” drug cocktail. After 6 hours of perfusion, defatted livers demonstrated lower perfusate lactate levels and improved bile quality as demonstrated by higher bile bicarbonate and lower bile lactate. Furthermore, defatting was associated with decreased gene expression of pro-inflammatory cytokines and increased expression of enzymes involved in mitochondrial fatty acid oxidation. Rehabilitation of marginal or discarded steatotic livers using machine perfusion and tailored drug therapy can significantly increase the supply of donor livers for transplantation.

Highlights

Liver transplantation remains the only cure for end-stage liver disease
DSL and SL groups had a similar rise in perfusate lactate content during the first two hours of perfusion, while the livers from lean rats (LL) group had a significantly slower rise as compared to the SL group
The anion gap of the perfusate increased initially in all three groups but decreased significantly in the LL and DSL groups starting at the 2nd hour of perfusion compared to the SL group (Fig 1B)

Summary

Introduction

Liver transplantation remains the only cure for end-stage liver disease. There continues to be a significant organ shortage with approximately 14, 000 patients on the waitlist and 8,000 liver transplants performed annually [1]. Central to the donor organ shortage is the high discard rate of procured or potentially procurable organs, with nearly 3,000 livers discarded per year [2]. As a result of the obesity epidemic in the United States and Europe, nearly half of procured livers are discarded due to excessive macrosteatosis related to non-alcoholic fatty liver disease (NAFLD) [3].

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Conclusion