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Liver transplantation is the only curative treatment option for patients with end-stage liver disease. However, demand for suitable donor organs far exceeds the supply, leading to a waitlist mortality approaching 20%. To address this, transplant programs have increasingly turned to suboptimal organs from extended criteria donors (ECD). While this expands the donor pool, these ECD livers are more vulnerable to damage from oxygen deprivation, making them higher risk for post-transplant complications. As a result, many of these high-risk organs are not considered for transplantation. To address this, machine perfusion of donor livers has gained significant attention. Machine perfusion involves circulation oxygenated fluid through the liver outside the body and can be performed at different temperatures. Cold (hypothermic) perfusion helps restore cellular energy and reduce injury, while warm (normothermic) perfusion reactivates metabolism, allowing real-time functional assessment, guiding the decision to transplant. Machine perfusion also offers a unique opportunity for therapeutic interventions to improve organ quality before transplantation. This thesis explores protein and gene profiles (proteomics and transcriptomics) to investigate molecular-level changes in donor livers during machine perfusion. These approaches make it possible to identify specific biomarkers and processes that more accurately reflect underlying mechanisms driving organ quality, injury, repair and the effects of therapeutic intervention. By providing a deeper, more objective understanding of perfused livers, this research investigates current machine perfusion strategies, and present molecular profiles that may provide clearer, more actionable understanding of organ quality and underlying processes in ECD livers.