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Effects of normothermic machine perfusion and de-fatting agents on human steatotic livers

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Summary of research outcomes

This study has demonstrated that hepatic lipid metabolism can be manipulated in the ex situ setting using normothermic machine perfusion in order to create an improved environment for steatotic liver preservation with enhanced function.

Through the addition of an apheresis filter to the circuit, a significant increase in hepatic arterial blood flow was observed, as well as significant reductions in circulating lipoproteins (namely triglyceride (TG) and cholesterol) and increase in hepatic glycogen content.

As well as the benefits of lipoprotein apheresis filtration, pharmacological intervention further improved arterial flow, significantly reduced circulating glucose levels, increased mitochondrial b-oxidation and reduced hepatic TG content.

It is likely that the reduction in TG content was due to increased fatty acid oxidation and a reduction in de novo lipogenesis.  

Objectives

To investigate the impact of de-fatting agents on ex situ liver function.

To explore the effects of de-fatting interventions on liver fat content.

To understand the potential mechanisms pertaining to any alteration in lipid metabolism and structure during NMP. 

Improvement to future patient care and treatment

This research study provides evidence to support the use of normothermic machine perfusion in the enhanced preservation of steatotic livers and it is hoped that through increased utilisation of these high risk organs, the number of waiting list deaths could be reduced.  

Dissemination of results

Study to be presented in the plenary transplant session at the American Association for the Study of Liver Disease (AASLD), San Francisco, November 2018. 

More information 

Email ODTresearch@nhsbt.nhs.uk for more information about this research.