An international evaluation of trends and outcomes of living donor liver transplantation: United States, United Kingdom, and Canada

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Presenter: Tommy Ivanics MD | University Health Network, Toronto General Hospital Background: Living donor liver transplantation (LDLT) offers an opportunity to decrease the liver transplant waitlist and reduce waitlist mortality. We sought to compare donor and recipient characteristics and post-transplant outcomes after LDLT in the United States (US), United Kingdom (UK), and Canada, where deceased donors provide the majority of organs available for transplantation. Methods: We studied adults (≥18-years) who underwent primary LDLT between Jan-2008 and Dec-2018 from three national liver transplantation registries: United Network for Organ Sharing (UNOS;US), National Health Service Blood and Transplantation (NHSBT;UK), and the Canadian Organ Replacement Registry (CORR;Canada). Patients undergoing re-transplantation, multi-visceral transplantation, or had waitlist drop-out were excluded. Recipient and donor characteristics were compared across countries. A non-parametric Cox-Stuart trend test for LDLT was performed in each country. Post-transplant survival was evaluated using the Kaplan-Meier method, and multivariable adjustments were performed using Cox Proportional Hazard models. Results: A total of 3,086 LDLTs were performed (US:n = 2,433; UK:n = 97; Canada:n = 556). A trend toward increased LDLT over time was present in the US (Cox-Stuart trend test: US: p = 0.08; UK:p = 0.73; Canada: p = 0.49). Overall, the proportion of LDLTs compared to other grafts has remained stable (Figure 1) with Canada maintaining the highest proportion over time (proportion of LDLT 2008: US 3.4%; UK:1.7%; Canada: 20.1%; p<0.001; 2018: US: 5.0%; UK: 0.4%; Canada: 13.8%; p<0.001). The US and Canadian recipients had the highest body mass index (median [IQR]], US 26 [23-30]; UK 24 [22-28]; Canada 26 [23-29]; overall p<0.001) and the highest donor age (years, median [IQR]: US 36 [28-45]; UK 33 [25-40]; Canada 35 [27-46]; overall p = 0.010). The laboratory Model for End-Stage Liver disease (MELD) score was highest in Canada (median [IQR]: US 15 [11-19]; UK 11 [8-18]; Canada 17 [13-21]; p<0.001). UK had a higher proportion of hepatitis C virus as disease etiology (US 2%; UK 21%; Canada 12%;p<0.001) whereas the US had a higher proportion of non-alcoholic steatohepatitis (US 17%; UK 11%; Canada 7%;p<0.001). Time on the waitlist was longest in the US (days, median [IQR]; US 151 [79-308]; UK 92 [7-202]; Canada 122 [64-230];overall p<0.001). At 1-year there was a non-statistically significant superior survival in Canada (1-year%[95%CI]]; US 93.0% [(92.0-94.1]; UK 91.4% [85.8-97.3]; Canada 95.8% [94.1-97.5];p = 0.06]. The 3-, 5-, 10-year survival rate was superior in Canada (3-year% [95%CI]; US 88.1% [86.8-89.5]; UK 90.0% [84.0-96.5]; Canada 92.1% [89.8-94.5];p = 0.04), (5-year%[95%CI]; US 83.5% [81.8-85.3]; UK 85.4% [77.1-94.5]; Canada 89.9% [87.1-92.7];p = 0.005), and (10-year%; US 71.1% [67.6-74.8]; UK 66.7% [45.0-98.8]; Canada 82.7% [78.2-87.5];p = 0.001). The median survival was not reached in any of the registries. After adjustment for characteristics of donors, recipients, annual center volume, and year of transplantation, all countries had an equivalent hazard of mortality post-LT ([HR] for mortality, US Reference, UK HR:1.26, 95%CI 0.67-2.39;p = 0.47; Canada HR:0.61,95%CI 0.30-1.26;p = 0.18). Stratification by hepatocellular carcinoma status did not alter the patterns observed in the data. Conclusion: LDLT use has remained stably low in western countries. Despite this, long-term survival is excellent. Continued efforts to increase LDLT in these countries is thus warranted due to the growing waitlist and differences in allocation that may disadvantage patients currently awaiting liver transplantation.