Assessment of deceased brain dead donor liver grafts via normothermic machine perfusion: Lactate clearance time threshold can be safely extended to six hours

Abstract Background Liver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in treatment following LT; however, they have limitations, including low colonization in the liver. An optimized BMMSC application method is required to suppress ACR. Methods BMMSCs were isolated and modified with the heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT into rats. The severity of ACR was evaluated based on liver histopathology. Gene chip technology was used to detect differential gene expression, and flow cytometry to analyze changes in natural killer (NK) T cells. Results NMP induced BMMSCs to colonize the donor liver during in vitro preservation. The survival of HO-1/BMMSCs in liver grafts was significantly longer than that of unmodified BMMSCs. When the donor liver contained HO-1/BMMSCs, the local immunosuppressive effect was improved and prolonged, ACR was controlled, and survival time was significantly prolonged. The application of HO-1/BMMSCs reduced the number of NKT cells in liver grafts, increased the expression of NKT cell co-inhibitory receptors, and reduced NKT cell expression of interferon-γ. Conclusions NK cell and CD8+ T cell activation was inhibited by application of HO-1/BMMSCs, which reduced ACR of transplanted liver. This approach could be developed to enhance the success rate of LT.

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Continuous Normothermic Machine Perfusion for Renovation of Extended Criteria Donor Livers Without Recooling in Liver Transplantation: A Pilot Experience

Frontiers in Surgery ◽

10.3389/fsurg.2021.638090 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhitao Chen ◽

Xitao Hong ◽

Shanzhou Huang ◽

Tielong Wang ◽

Yihao Ma ◽

...

Keyword(s):

Acute Hepatic Failure ◽

Meld Score ◽

Decompensated Cirrhosis ◽

Machine Perfusion ◽

Donor Liver ◽

Extended Criteria Donor ◽

Allograft Function ◽

Normothermic Machine Perfusion ◽

End Stage ◽

Early Allograft Dysfunction

Background: Ischemia injury affects the recovery of liver allograft function. We propose a novel technique aimed at avoiding a second ischemic injury: transplanting an extended criteria donor (ECD) liver directly under normothermic machine perfusion (NMP) without recooling. We studied two cases to evaluate the efficacy and safety of this technique.Methods: The perioperative characteristics and postoperative outcomes of two recipients of ECD livers were analyzed. Both transplantations were performed with continuous normothermic machine perfusion without recooling.Result: In case 1, the cause of donor death was anoxia, and the donor liver had hypernatremia before procurement. The recipient was diagnosed with decompensated cirrhosis. His model for end-stage liver disease (MELD) score was 38. In case 2, the donor liver was from a donor after cardiac death (DCD), and the donor had elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. The recipient was diagnosed with acute hepatic failure. His MELD score was 35. Both donor livers were maintained under NMP and then transplanted without recooling. The peak ALT and AST levels after surgery were 452 and 770 U/L in case 1 and 100 and 592 U/L in case 2. Neither early allograft dysfunction (EAD) nor primary graft non-function (PNF) was present in these two cases.Conclusion: In conclusion, our results demonstrate that continuous NMP without recooling is efficacious and safe for LT with extended criteria donor livers. Further investigations of this technique will be performed to confirm these promising results.

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Experimental perfusion device for preservation of donor’s liver

Grekov s Bulletin of Surgery ◽

10.24884/0042-4625-2017-176-3-88-92 ◽

2017 ◽

Vol 176 (3) ◽

pp. 88-92

Author(s):

S. F. Bagnenko ◽

O. N. Reznik ◽

A. E. Skvortsov ◽

A. V. Lopota ◽

N. A. Gryaznov ◽

...

Keyword(s):

Biochemical Parameters ◽

Warm Ischemia ◽

Central Research ◽

Machine Perfusion ◽

Clinical Tests ◽

Donor Liver ◽

Porcine Liver ◽

Design Institute ◽

Normothermic Perfusion ◽

Normothermic Machine Perfusion

OBJECTIVE. The authors aimed to develop complex perfusion medical device in order to successfully maintain viability of donor liver until transplantation. MATERIAL AND METHODS. Experimental perfusion device for normothermic perfusion donor’s liver was developed and tested in the Central Research and Experimental-design Institute of Robotics and Technical Cybernetics. RESULTS. The pre-clinical tests were performed on porcine liver. It was demonstrated that normothermic machine perfusion could restore liver function after 30 minutes of warm ischemia time and provide normalization of biochemical parameters of organ functioning.

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A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion

Scientific Reports ◽

10.1038/s41598-021-02641-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ivo J. Schurink ◽

Jubi E. de Haan ◽

Jorke Willemse ◽

Matteo Mueller ◽

Michael Doukas ◽

...

Keyword(s):

Liver Function ◽

Breath Test ◽

Ex Vivo ◽

Graft Function ◽

Inverse Correlation ◽

Lactate Clearance ◽

Liver Graft ◽

Machine Perfusion ◽

Reliable Parameter ◽

Normothermic Machine Perfusion

AbstractNo single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = − 0.874, P < 0.001), AST (R = − 0.812, P = 0.004) and ALT (R = − 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts.

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