Impact of Prolonged Cold Ischemia on Liver Graft Function in Liver Transplantation: A Systematic Review
Keywords:
Cold Ischemia, Liver Graft, Liver TransplantationAbstract
Objective: To evaluate and compare the effectiveness of different preservation and preconditioning strategies in reducing the deleterious effects of prolonged cold ischemia in liver transplantation, analyzing their impact on graft dysfunction, post-transplant clinical outcomes, and recipient-associated risk factors. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches were performed in the PubMed, Virtual Health Library, and Cochrane Library databases, last updated in February 2025, resulting in the initial identification of 198 studies. Clinical trials, observational studies, and meta-analyses published in the last 5 years, analyzing the impact of cold ischemia on liver transplantation, were included. After rigorous screening, 10 articles were selected, excluding studies considered irrelevant, with small sample sizes or inadequate methodology. Results: Prolonged cold ischemia (PCI) is associated with graft dysfunction, cellular necrosis, inflammation, increased need for clinical support, and higher costs. Strategies such as hypothermic oxygenated perfusion (HOPE), use of the portable Organ Care System (OCS), remote ischemic preconditioning, and N-acetylcysteine (NAC) infusion showed potential to mitigate PCI effects. Factors such as ethnicity, sex, age, and transport time also influence outcomes. The adoption of these strategies may reduce post-transplant complications and improve graft survival. Conclusion: The review demonstrated that PCI is a consistent determinant of early graft dysfunction in liver transplantation, influencing ischemia–reperfusion injury, inflammation, and biliary complications. Although only one study evaluated cold ischemia time (CIT) as the primary variable, all included studies confirmed its role as a risk factor or adjusted variable. Technologies such as HOPE, OCS, NAC, and ischemic preconditioning may attenuate its effects but do not fully eliminate them. Thus, reducing CIT, combined with modern preservation strategies and appropriate donor selection, remains essential to improving liver transplant outcomes.
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Copyright (c) 2026 Yohanna Monise dos Santos Rodrigues, Larissa Avila Branco, Giovanna Batista Messas, Juliana Góes Fernandes, Laura Almeida Vidal, Rebeca Soares Almeida, Gustavo Oliva de Sá
This work is licensed under a Creative Commons Attribution 4.0 International License.
