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19th

International Liver Support Meeting Rostock

Hepatoma conditioning for normothermic transplant recovery perfusion

The demand for suitable donors for liver transplantation continues to increase globally. Transplant teams are becoming more reliant on marginal or extended criteria donor livers, the utilization of which varies hugely as their use is associated with complications. The extracorporeal liver assist system (ELAD®, Vital Therapies©, San Diego, United States) has shown promise in supplementing hepatic function in patients with liver failure. The secretome of the VTL C3A cells is thought to contain soluble molecules that may also be beneficial to marginal livers. 

A collaboration was formed between the University of Birmingham, Vital Therapies and Drexel University to undertake a series of normothermic perfusions of marginal donor livers, using VTL CT3A conditioned media (CT3A CM) as the colloid within the perfusate. Organ viability was assessed using established criteria and compared, along with perfusion characteristics, to a series of historical controls. Histology, immunohistochemistry and proteomic analysis of the perfusates were also analysed. 

To date, at UoB, 5 marginal discarded human livers have been perfused with a blood-based perfusate containing CT3A CM. Four of the five livers met viability criteria and this included 2 very marginal steatotic DCD’s with prolonged cold ischemic times. Histology demonstrated maintenance of parenchymal architecture throughout the perfusion and increases in glycogen storage in all 5 livers. When compared to that of historical controls, proteomic analysis yielded 58 unique proteins which functional enrichment analysis linked to several important biological, metabolic and cellular pathways. A body of in vitro work using CT3A CM to culture of primary liver cells has also shown some promising results. CT3A CM can be used in machine perfusion fluid and may contain beneficial soluble mediators that could recondition marginal donor livers prior to transplantation. 

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