The Differential Influence of Cold Ischemia Time on Outcome After Liver Transplantation for Different Indications—Who Is at Risk? A Collaborative Transplant Study Report

Introduction: Despite increasing awareness of the negative impact of cold ischemia time (CIT) in liver transplantation, its precise influence in different subgroups of liver transplant recipients has not been analyzed in detail. This study aimed to identify liver transplant recipients with an unfavorable outcome due to prolonged cold ischemia. Methods: 40,288 adult liver transplantations, performed between 1998 and 2017 and reported to the Collaborative Transplant Study were analyzed. Results: Prolonged CIT significantly reduced graft and patient survival only during the first post-transplant year. On average, each hour added to the cold ischemia was associated with a 3.4% increase in the risk of graft loss (hazard ratio (HR) 1.034, P<0.001). The impact of CIT was strongest in patients with hepatitis C-related (HCV) cirrhosis with a 24% higher risk of graft loss already at 8–9 hours (HR 1.24, 95% CI 1.05–1.47, P=0.011) and 64% higher risk at ≥14 hours (HR 1.64, 95% CI 1.30–2.09, P<0.001). In contrast, patients with hepatocellular cancer (HCC) and alcoholic cirrhosis tolerated longer ischemia times up to <10 and <12 hours, respectively, without significant impact on graft survival (P=0.47 and 0.42). In HCC patients with laboratory model of end-stage liver disease scores (labMELD) <20, graft survival was not significantly impaired in the cases of CIT up to 13 hours. Conclusion: The negative influence of CIT on liver transplant outcome depends on the underlying disease, patients with HCV-related cirrhosis being at the highest risk of graft loss due to prolonged cold ischemia. Grafts with longer cold preservation times should preferentially be allocated to recipients with alcoholic cirrhosis and HCC patients with labMELD <20, in whom the effect of cold ischemia is less pronounced.