Strategies for expanding organ availability and improving transplant outcomes

Organ transplantation is a lifesaving treatment for patients suffering from end stage liver disease or heart failure. For patients with chronic kidney disease, transplantation reduces morbidity and decreases mortality. Successful organ transplantation programs are directly dependent on a sufficient supply of organs to meet the increasing demands. In addition, our smallest patients are at an increased risk of mortality while waiting for an organ transplantation due to the lack of size matched organs.

This thesis focuses on avenues of expanding organ availability to enable more transplantations, as well as improving the outcomes after transplantation.

Study I investigate risk factors for increased time of waiting and mortality while on the waiting list for a liver transplantation within Scandiatransplant. We could show that although Scandiatransplant utilizes an efficient and fair organ allocation system for liver, patient ABO blood group was strongly associated with both increased time of waiting and mortality.

In study II we implemented and evaluated a controlled donation after circulatory death (cDCD) liver transplant program, utilizing normothermic regional perfusion. Here, we could show a successful implementation of a nationwide protocol and an increase in available livers for transplantation. In addition, we compared the outcomes to a retrospective cohort receiving liver transplants from brain dead donors. Our results show excellent patient and graft survival as well as a low level of biliary complications, further supported by magnetic resonance imaging.

Study III and study IV focuses on the possibility of implementing neonatal organ donation in Sweden. In study III, using the Swedish Neonatal Quality Registry and digital medical records, we identified all potential donors. After applying organ specific criteria, we could show a potential of neonatal organ donation in central Sweden, which could significantly increase available organs. Thereafter in study IV, we successfully implemented a neonatal organ donation after circulatory death (DCD) program, showing that such a program is possible within the Swedish context. Here, we procured 12 livers, whereby we isolated and evaluated the hepatocytes after transplanting them into a humanized mouse model. We could show that neonatal hepatocytes were of excellent quality, resulting in a high yield, and resistance to cryopreservation injury. After hepatocyte transplantation into a humanized mouse model, we could show signs of continued maturation as well as function after transplantation.

List of scientific papers

I. Bluhme E, Renneus Guthrie V, Duus Weinreich I, Hagstršm H, Line PD, Isoniemi H, Bennet W, Rasmussen A, Ericzon BG, Melum E, and, Jorns C. Factors associated with waiting time and mortality on liver transplant waiting lists within Scandiatransplant Đ a multicenter cohort study. [Submitted]

II. Bluhme E, GŠbel M, Martinez L, Nilsen V, Hildebrand K, JarsŠter J, BŚŚth C, Proos M, Romano A, Villard C, Oniscu G, Gustaffson N, Thomsen M, Hansson C, Lšfstedt M, Andersson Lindholm J, Falk L, Bennet W, and Jorns C. Normothermic regional perfusion in controlled DCD liver procurement: outcomes of the Swedish national implementation protocol. Liver Transplantation. 2024.
https://doi.org/10.1097/LVT.0000000000000434

III. Bluhme E, Henckel E, Hallberg B, and Jorns C. The potential of neonatal organ donation in Central Sweden. [Submitted]

IV. Bluhme E, Henckel E, Gramignoli R, Kjellin T, Hammarstedt C, Nowak G, Karadagi A, Johansson H, Jynge …, Sšderstršm M, Fischler B, Strom S, Ellis E, Hallberg B and Jorns C. Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death. Cell Transplant. 2022 Jan-Dec;31:9636897211069900.
https://doi.org/10.1177/09636897211069900