Donor hepatectomy time influences ischemia-reperfusion injury of the biliary tree in donation after circulatory death liver transplantation

Otto B Van Leeuwen,Marjolein Van Reeven,Danny Van Der Helm,Jan N.M Ijzermans,Vincent E De Meijer,Aad P Van Den Berg,Sarwa Darwish Murad,Bart Van Hoek,Ian P.J Alwayn,Robert J Porte,Wojciech G Polak

doi:10.1016/j.surg.2020.02.005

Abstract

BackgroundDonor hepatectomy time is associated with graft survival after liver transplantation. The aim of this study was to identify the impact of donor hepatectomy time on biliary injury during donation after circulatory death liver transplantation. MethodsFirst, bile duct biopsies of livers included in (pre)clinical machine perfusion research were analyzed. Secondly, of the same livers, bile samples were collected during normothermic machine perfusion. Lastly, a nationwide retrospective cohort study was performed including 273 adult patients undergoing donation after circulatory death liver transplantation between January 1, 2002 and January 1, 2017. Primary endpoint was development of non-anastomotic biliary strictures within 2 years of donation after circulatory death liver transplantation. Cox proportional-hazards regression analyses were used to assess the influence of hepatectomy time on the development of non-anastomotic biliary strictures. ResultsLivers with severe histological bile duct injury had a higher median hepatectomy time (P = .03). During normothermic machine perfusion, livers with a hepatectomy time >50 minutes had lower biliary bicarbonate and bile pH levels. In the nationwide retrospective study, donor hepatectomy time was an independent risk factor for non-anastomotic biliary strictures after donation after circulatory death liver transplantation (Hazard Ratio 1.18 per 10 minutes increase, 95% Confidence Interval 1.06–1.30, P value = .002). ConclusionDonor hepatectomy time negatively influences histological bile duct injury before normothermic machine perfusion and bile composition during normothermic machine perfusion. Additionally, hepatectomy time is a significant independent risk factor for the development of non-anastomotic biliary strictures after donation after circulatory death liver transplantation.

Highlights

The imbalance between the number of patients on the waiting list for liver transplantation (LT) and the number of available grafts from donation after brain death (DBD) donors has resulted in an increased use of livers from donation after circulatory death (DCD)O.B. van Leeuwen et al / Surgery xxx (2020) 1e7 donors
LT from DCD donors can lead to inferior outcomes compared with LT with DBD grafts, especially with respect to graft survival,2e5 which is related to a higher chance of developing early allograft dysfunction and post-transplant cholangiopathy.6e10 Among posttransplant cholangiopathies, non-anastomotic strictures (NAS), known as ischemic type biliary lesions or ischemic cholangiopathy, is the most hazardous type, with a strong negative impact on graft survival.11e13
Donor age and cold ischemia time were significant risk factors for NAS. This is the first study that demonstrates the impact of donor hepatectomy time on the development of biliary injury during and after DCD liver transplantation

Summary

Introduction

The imbalance between the number of patients on the waiting list for liver transplantation (LT) and the number of available grafts from donation after brain death (DBD) donors has resulted in an increased use of livers from donation after circulatory death (DCD)O.B. van Leeuwen et al / Surgery xxx (2020) 1e7 donors. The aim of this study was to identify the impact of donor hepatectomy time on biliary injury during donation after circulatory death liver transplantation. Primary endpoint was development of non-anastomotic biliary strictures within 2 years of donation after circulatory death liver transplantation. In the nationwide retrospective study, donor hepatectomy time was an independent risk factor for non-anastomotic biliary strictures after donation after circulatory death liver transplantation (Hazard Ratio 1.18 per 10 minutes increase, 95% Confidence Interval 1.06e1.30, P value 1⁄4 .002). Hepatectomy time is a significant independent risk factor for the development of non-anastomotic biliary strictures after donation after circulatory death liver transplantation

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Conclusion