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

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3 Scopus citations

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.

Original languageEnglish (US)
Article numbere0232886
JournalPloS one
Volume15
Issue number5
DOIs
StatePublished - May 2020

Bibliographical note

Funding Information:
MY, KU, and HY received funding from the US National Institutes of Health (grants R01DK096075, R01DK107875, R21EB020819, R01DK084053 and R01DK114506). The funders had no role in study design, data collection, analysis, or manuscript preparation. We would like to thank the Mass Spectrometry Core at Shriners Hospital for Children for processing our samples, as well as, Brian Healy PhD and the Harvard Catalyst Clinical/Translational Research Academy for statistical support.

Publisher Copyright:
© 2020 Raigani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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