Liver transplantation outcomes within the practice of medical assistance in dying (MAiD) - manuscript-based thesis

Introduction: Liver transplantation aims to treat end-stage liver disease and its complications but is limited by ongoing shortages in availability of donor organs. Liver transplantation in the context of medical assistance in dying (MAiD) is an emerging practice, with Canada being one of the few countries worldwide where MAiD organ donation occurs. MAiD organ recovery is a type of donation after circulatory death (DCD), though it differs from standard DCD in both donor characteristics and logistical processes. For the purposes of this report, “DCD” refers specifically to the conventional DCD pathway involving the withdrawal of life-sustaining measures followed by rapid organ recovery, whereas “MAiD” refers to the DCD after MAiD pathway. In 2017, MAiD organ donation began in Quebec, but it remains unclear whether MAID liver recipients have increased complications in comparison to other modes of donation. The current Quebec MAiD context allows for a unique opportunity to evaluate liver transplantation outcomes within the practice of MAiD organ donation and inform future practices where MAiD will become available. Objectives:To compare outcomes of adult liver transplant recipients from MAiD, standard DCD, and donation after brain death (DBD) donors, with a focus on biliary complications. Methods: Ethics approval was obtained under the McGill University Health Centre prior to the initiation of this study. Following ethics approval, a retrospective cohort study was conducted to include consecutive liver transplant donors and recipients between January 2018 and March 2024. Recipients were classified by donor type: MAiD, DCD, or DBD. Re-transplants and multi-organ transplants were excluded. Pre-operative variables included donor/recipient age, sex, BMI, cause of death, liver disease etiology, Charlson Comorbidity Index, MELD-Na, location, and ventilation status pre-transplant. Peri-operative variables included transfusions, operative times, ischemia times, and operative blood loss. Primary outcomes were graft /patient survival, and primary liver non-function. Secondary outcomes included early allograft dysfunction (Olthoff criteria), vascular complications, biliary complications (leaks, strictures, ischemic cholangiopathy, and hepatic duct stones, need for ERCP, and percutaneous biliary drain insertion), and Clavien-Dindo scores. Kaplan-Meier survival analysis and multi-variate Cox regression were performed to look for predictors of patient mortality and graft loss. Results: We included 177 liver transplant recipients (19 MAiD, 14 DCD, 144 DBD). All MAiD donors had neurodegenerative conditions. MAiD and DBD donors were significantly older than DCD donors (mean age 59, 57 vs 37; p<0.001) and had lower median BMI than other donors (20 kg/m2 vs 22 DCD and 26 DBD; p<0.001). Recipient variables were similar across groups. Cold ischemia times were longest for DBD grafts (6.6 hours vs 6.2 DCD and 5.8 MAiD; p=0.02), with no other intraoperative differences. Mortality ≤90 days were comparable amongst all groups (p=0.72). One-year Clavien-Dindo complications (Grade ≥3) and re-transplant rates were comparable across groups. Biliary strictures were the most common complication: 42% MAiD, 35% DCD, vs 13% DBD (p=0.005), mostly extrahepatic and anastomotic. Kaplan-Meier analysis showed no significant difference in graft survival between donor groups (p=0.74), Cox regression identified portal vein thrombosis (HR 23.98; 95%: CI 2.41-238.15), hepatic artery thrombosis (HR 8.14; 95% CI 1.72-38.54), and biliary complications (HR: 11.93; 95% CI 2.31-61.76) as independent predictors of graft loss. MAiD donor type was not associated with increased patient mortality or graft failure.Discussion: This is the largest Canadian series on MAiD liver transplants to date. In alignment with the existing literature, graft survival outcomes for MAiD donor recipients in this study were comparable to DCD and DBD groups. Unlike DCD donors, MAiD donors in this series were older, possibly challenging previous assumptions that younger donors are preferable when using MAiD liver organs. Biliary strictures were more frequent in MAiD recipients vs. DBD recipients, but comparable to DCD recipients, likely due to donor warm ischemia, a known risk factor in DCD donation. Among recipients of MAiD liver donors who developed biliary complications, the majority (7/8, 88%) were successfully managed with ERCP. These findings align with the few earlier Canadian studies and reinforce the safety profile of MAiD liver grafts. The use of machine perfusion may help to reduce biliary complications and optimize outcomes.Conclusion: This study contributes to the limited available North American literature on MAiD liver transplantation and demonstrates promising graft and patient outcomes. Current evidence supports the continued use and expansion of MAiD liver donation

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