When Machine Perfusion Falls Short: Identifying Risks of Liver Graft Failure After Normothermic Machine Perfusion

BACKGROUND: Machine perfusion technology has redefined donor and recipient criteria for liver transplantation. Despite increasing adoption, data regarding graft and recipient factors associated with unsuccessful normothermic machine perfusion (NMP) outcomes remain limited. METHODS: The Organ Procurement and Transplantation Network database was used to retrospectively identify adult patients undergoing deceased donor liver transplantation with NMP preservation between January 10, 2021, and December 31, 2024. Populations were stratified by 1-year graft status, with donor and recipient factors compared. Logistic regression identified factors independently associated with NMP graft failure, and center analyses assessed program-level impacts. RESULTS: Among 4928 NMP cases, 398 (8.1%) experienced 1-year graft failure. They were more frequently admitted to the intensive care unit (ICU) at transplant (21.1% vs. 10.6%, p < 0.001) and had more complex abdominal histories, including higher rates of TIPS(17.0% vs. 12.0%), prior abdominal surgery (64.1% vs. 54.7%), and prior liver transplant (10.3% vs. 3.4%) (all p < 0.01). Regression analysis identified increased odds of graft failure with MELD score 35 (aOR 2.10 [1.21-3.63]), low recipient functional status (aOR 2.05 [1.31-3.21]), and prior abdominal surgery (aOR 1.33 [1.01-1.76]). Alcohol-associated liver disease (aOR 0.36 [0.23-0.56]) was the only factor conferring a protective effect. Centers with higher-than-expected standardized NMP graft failure rates were higher-volume programs with low-risk case mixes; no centers had persistently high standardized failure rates throughout the study period. CONCLUSION: Recipient factors, particularly those conferring surgical complexity, are more significantly associated with NMP graft failure than donor factors. Despite increased adoption of perfusion technologies to mitigate donor and operative risk, transplant provider clinical judgment remains critical for optimizing recipient-donor matching and outcomes.