Matrix metalloproteinase 9 associates with post-transplant liver injury despite attenuation by normothermic machine perfusion.

Matrix metalloproteinase-9 (MMP-9) facilitates leukocyte infiltration during hepatic ischemia-reperfusion injury (IRI), and its inhibition mitigates injury in experimental models, underscoring its therapeutic potential in liver transplantation. Normothermic machine perfusion (NMP) offers a unique opportunity to modulate inflammatory pathways during organ preservation and represents a potential window for MMP-9-targeted intervention. Compared with 10 livers preserved by static cold storage, 30 NMP-preserved livers showed a markedly attenuated rise in plasma MMP-9 after reperfusion. In both preservation strategies, elevated MMP-9 was consistently associated with biochemical and clinical indicators of IRI, including hepatocellular injury, post-operative liver- and kidney dysfunction. Pro-MMP-9 was detected exclusively in recipients who developed early allograft dysfunction, graft failure, and/or death, suggesting a role in driving severe injury. In an independent cohort, perfusate and biliary MMP-9 in 10 NMPs reflected post-transplant cholestasis and subsequent biliary complications. Together, these findings identify MMP-9 as a relevant biomarker and a potential therapeutic target during machine perfusion.