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

Vladimir J Lozanovski,Bernd Döhler,Arianeb Mehrabi,Caner Süsal,Karl Heinz Weiss

doi:10.3389/fimmu.2020.00892

Vladimir J Lozanovski, Bernd Döhler + Show 3 more

Open Access

https://doi.org/10.3389/fimmu.2020.00892

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Abstract

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 h (HR 1.24, 95% CI 1.05–1.47, P = 0.011) and 64% higher risk at ≥14 h (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 h, respectively, without significant impact on graft survival (P = 0.47 and 0.42). In HCC patients with model of end-stage liver disease scores (MELD) <20, graft survival was not significantly impaired in the cases of CIT up to 13 h.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 MELD <20, in whom the effect of cold ischemia is less pronounced.

Highlights

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
Alcoholic cirrhosis gained continuously on incidence and has become the second most common underlying disease that led to liver transplantation since 2014
Outcome of a graft depends on its ability to recover from the ischemia injury, which appears to be especially difficult in steatotic grafts or grafts from older donors [12,13,14]

Summary

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. Organs with prolonged cold ischemia are often discarded as unsuitable for transplantation [2] To address this problem, we suggested an allocation algorithm that balances the maEDC with the recipient’s health condition, and considers maEDC grafts an acceptable alternative for transplant candidates with lower laboratory Model of End-Stage Liver Disease (labMELD) scores who generally are in a better condition [2]. This study aimed to identify liver transplant recipients whose grafts are less affected from a prolonged cold ischemia, and to describe risk factors associated with an adverse outcome following transplantation of such organs

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