Background: The active metabolism during normothermic ex vivo liver perfusion (NEVLP) offers a new opportunity to use the preservation time for graft modification and repair strategies. One possible strategy, as “proof of concept”, is the induction of resistance against infection Hepatitis C virus (HCV). HCV replication is dependent on the presence of miRNA-122. Miravirsen, a locked-nucleic acid oligonucleotide, sequesters miR-122 and inhibits HCV replication.

Methods: Pig livers were treated with miravirsen during NEVLP or cold storage (CS) and miravirsen absorption, miR-122 sequestration and miR-122 target gene derepression were assessed before and after LT.

Results: In vitro data confirmed miravirsen suppression of HCV replication after established infection and prevented HCV infection with pre-treatment of cells, analogous to the pre-treatment of grafts in the transplant setting. NEVLP improved miravirsen uptake compared to CS Significant miR-122 sequestration (p<0.05) and miR-122 target gene derepression (p<0.01) were seen with NEVLP but not with CS prior to pig LT. Conclusion: NEVLP provides a novel platform for graft modification, such as inducing resistance against HCV infection, using nucleic acid oligonucleotide.

CITATION INFORMATION: Goldaracena N, Echeverri J, Selzner N, Grant D, Feld J, Selzner M. A Proof of Concept for Liver Graft Modification Using Warm Ex Vivo Perfusion – “It Is Not Just About Rescuing Marginal Grafts”. Am J Transplant. 2017;17 (suppl 3).

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