Survival of Patients With Liver Transplants Donated After Euthanasia, Circulatory Death, or Brain Death at a Single Center in Belgium

Transplantation of organs donated after euthanasia may help alleviate the critical organ shortage.¹ However, aside from preliminary data on lung transplantation,² data on graft and patient survival following transplantation of organs donated after euthanasia are unavailable. Because donation after euthanasia entails a period of detrimental warm ischemia that hampers graft survival, similar to donation after circulatory death,³ results after transplantation of this type of graft need to be carefully evaluated.

The 2002 Belgian Euthanasia Act legalized euthanasia in Belgium for patients who experience unbearable physical or mental suffering because of an irremediable illness and who are able to deliberately, voluntarily, and repeatedly express their euthanasia request.⁴ In 2009, the liver transplant unit at the University Hospitals Leuven started including donor livers from individuals who had voluntarily requested to donate their organs after euthanasia. We report on the clinical outcome of the initial series of liver transplants donated after euthanasia.

We retrospectively reviewed data for all adult solitary livers transplanted at the University Hospitals Leuven between January 1, 2009, and December 31, 2015, and compared donor and recipient characteristics, ischemia time, and 3-year graft and patient survival after transplantation of livers obtained after donor euthanasia, circulatory death, or brain death. Graft loss was defined as retransplantation or graft failure leading to a recipient’s death. The final date of follow-up was April 25, 2019.

Continuous variables were analyzed using Kruskal-Wallis 1-way analysis of variance or Mann-Whitney U test, categorical variables were analyzed using χ² or Fisher exact test, and graft and patient survival were analyzed using Kaplan-Meier curves and log-rank test. A 2-sided P < .05 was considered statistically significant. Analyses were performed using SPSS version 20 (IBM) and Prism version 8 (GraphPad Software). All transplant recipients provided written informed consent for data collection, and the study was approved by the University Hospitals Leuven’s ethical committee.

Among 409 transplantations performed, 320 livers (78%) were donated after brain death, 78 (19%) after circulatory death, and 11 (2.7%) after euthanasia (Table), with donor median ages of 56 years (interquartile range [IQR], 46-68 years), 53 years (IQR, 44-61 years), and 44 years (IQR, 33-58 years), respectively (P = .09). All donor-related characteristics except for peak aspartate aminotransferase were similar among groups. Compared with livers donated after euthanasia, livers donated after circulatory death had longer median total donor warm ischemia time (20 minutes [IQR, 15-25 minutes] vs 13 minutes [IQR, 12-15 minutes]; P = .001) and longer median agonal warm ischemia time (10 minutes [IQR, 7-16 minutes] vs 3 minutes [IQR, 1-9 minutes]; P = .001), while median asystolic warm ischemia time was comparable. The median cold ischemia time during liver transplantation from euthanasia donors (4.84 hours [IQR, 4.10-6.20 hours]) was similar to that of circulatory death donors (5.30 hours [IQR, 4.58-6.25 hours]; P = .99) but was shorter than that of brain death donors (7.75 hours [IQR, 6.05-9.08 hours]; P = .002).

The median ages of recipients undergoing transplantation with livers donated after brain death, circulatory death, and euthanasia were 58 years (IQR, 48-65 years), 61 years (IQR, 52-66 years), and 64 years (IQR, 51-68 years), respectively (P = .33). The Model for End-stage Liver Disease score was similar between groups.

Liver transplantation after donor brain death, circulatory death, or euthanasia resulted in 3-year graft survival of 80.2% (95% CI, 75.4%-84.2%), 82% (95% CI, 71.6%-89%), and 90.9% (95% CI, 50.8%-98.7%) (P = .67) and 3-year patient survival of 86.1% (95% CI, 81.9%-89.5%), 84.6% (95% CI, 74.5%-91%), and 90.9% (95% CI, 50.8%-98.7%) (P = .84), respectively (Figure).

This retrospective analysis showed that medium-term graft and patient survival following transplantation of livers donated after euthanasia was similar to the survival observed following donation after circulatory death and after brain death. Although time to circulatory arrest is generally longer for donation following circulatory death, livers donated after euthanasia are still exposed to a period of warm ischemia, which increases the risk of posttransplantation complications and graft loss. As such, livers donated after euthanasia should still be considered high-risk livers, and, similar to donation after circulatory death, precautions such as minimization of cold ischemia time should be continued.⁵ These data support the notion that within a very strict ethicolegal and logistic framework, donation after euthanasia may represent a valuable source of donor organs. The small sample size, limited follow-up, and monocentric nature of the study preclude definitive conclusions but provide a rationale for larger, longer-term studies on efficacy and safety of donation after euthanasia.

Accepted for Publication: April 27, 2019.

Corresponding Author: Diethard Monbaliu, MD, PhD, Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium (diethard.monbaliu@uzleuven.be).

Author Contributions: Dr Monbaliu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Monbaliu, Gilbo, Jochmans, Jacobs-Tulleneers-Thevissen, Sainz-Barriga, Pirenne.

Acquisition, analysis, or interpretation of data: Monbaliu, Gilbo, Jochmans, Wolthuis, Pirenne.

Drafting of the manuscript: Monbaliu, Gilbo.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Monbaliu, Gilbo.

Administrative, technical, or material support: Jacobs-Tulleneers-Thevissen, Wolthuis.

Supervision: Monbaliu, Wolthuis, Sainz-Barriga, Pirenne.

Conflict of Interest Disclosures: Dr Jochmans reported support for congress attendance from Astellas. No other disclosures were reported.

Additional Contributions: We thank the donors and their families. We acknowledge the clinicians and transplant coordinators from the Leuven Transplantation Team who were involved in donation after euthanasia and transplantation procedures as well as in development of the ethical and procedural road map: from the University Hospitals Leuven: Emilio Canovai, MD, Laurens Ceulemans, PhD, Dirk Claes, RN, Karlien Degezelle, RN, Bruno Desschans, RN, Stijn Dirix, RN, Nele Grossen, RN, Paula Rioja, MD, and Glen Van Helleputte, RN (Department of Abdominal Transplantation Surgery and Coordination); David Cassiman, PhD, Wim Laleman, PhD, Frederik Nevens, PhD, Schalk Van der Merwe, PhD, Hannah Van Malenstein, PhD, Len Verbeke, PhD, and Chris Verslype, PhD (Department of Gastroenterology and Hepatology); Patrick Ferdinande, PhD (Department of Intensive Care Medicine); Arne Heylen, PhD, Johan Menten, PhD, and Walter Rombouts, PhD (Departments of Radiotherapy and Palliative Care); Arne Neyrinck, PhD, and Marleen Verhaeghe, PhD (Department of Anesthesiology); Dirk Van Raemdonck, PhD (Transplantation Council); from KU Leuven: Martin Hiele, PhD (Medical Ethical Committee); Herman Nys, PhD, and Paul Schotsmans, PhD (Center of Biomedical Ethics and Law); and from University Psychiatric Center: Joris Vandenberghe, PhD. None received financial compensation for their contribution to this study.