P-L17 Post-liver transplant inferior vena cava stenosis in a large volume UK centre

Background Inferior vena cava stenosis (IVCS) is a rare complication of liver transplantation with a reported incidence rate of 3%. Limited clinical consensus exists on the management of IVCS. We report the management and outcomes of patients with IVCS at our transplant centre. Methods Relevant data were collected from adult patients who underwent liver transplantation at our centre between October 2014 and August 2020. These included demographics, investigation and management details with regards to IVCS. Values presented as % of total and median with interquartile range (IQR). Results A total of 636 liver transplants were performed during the study period, of which 48 (7.6%) patients were investigated for possible IVCS. Of those, 14 (2.2% of total) were found to have IVCS, 85.7% (n = 12) were female. Only 2/14 were re-transplants and pre-transplant portal vein thrombus was present in 3 cases (21.4%). 10 livers (71.4%) were DBD donors. Normothermic machine perfusion was used in 4/14 patients. All 14 recipients found to have IVCS had had an implantation using a modified piggyback cavocavostomy technique. The IVCS was identified at a median of 25.5 days (19.7-30.8 days) following transplantation within the suprahepatic IVC in 92.9% (n = 13). Hemi-azygos collateralisation was seen in 4 cases (28.6%). 8 of the 14 recipients underwent intervention for IVCS, 6 patients were managed with balloon venoplasty, 1 patient required an IVC stent and 1 was managed surgically. Six of the recipients with IVCS died, 4 of whom had an intervention for their stenosis and 3 of these were within 90 days of their transplant. Pressures measured at the anastomotic stricture were higher in those who succumbed (median of 21 Vs 12.5 mmHg; p=.017). Conclusions At our centre, cava-replacement technique was not associated with IVCS. Patients with more significant strictures (as evidenced by higher pressures at the anastomotic stenosis) may have an increased mortality risk.

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

No 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.

The effect of blood cells retained in rat livers during static cold storage on viability outcomes during normothermic machine perfusion

In transplantation, livers are transported to recipients using static cold storage (SCS), whereby livers are exposed to cold ischemic injury that contribute to post-transplant risk factors. We hypothesized that flushing organs during procurement with cold preservation solutions could influence the number of donor blood cells retained in the allograft thereby exacerbating cold ischemic injury. We present the results of rat livers that underwent 24 h SCS after being flushed with a cold University of Wisconsin (UW) solution versus room temperature (RT) lactated ringers (LR) solution. These results were compared to livers that were not flushed prior to SCS and thoroughly flushed livers without SCS. We used viability and injury metrics collected during normothermic machine perfusion (NMP) and the number of retained peripheral cells (RPCs) measured by histology to compare outcomes. Compared to the cold UW flush group, livers flushed with RT LR had lower resistance, lactate, AST, and ALT at 6 h of NMP. The number of RPCs also had significant positive correlations with resistance, lactate, and potassium levels and a negative correlation with energy charge. In conclusion, livers exposed to cold UW flush prior to SCS appear to perform worse during NMP, compared to RT LR flush.

HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats

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.

Advances in Hypothermic and Normothermic Perfusion in Kidney Transplantation

Hypothermic and normothermic machine perfusion in kidney transplantation are purported to exert a beneficial effect on post-transplant outcomes compared to the traditionally used method of static cold storage. Kidney perfusion techniques provide a window for organ reconditioning and quality assessment. However, how best to deliver these preservation methods or improve organ quality has not yet been conclusively defined. This review summarises the promising advances in machine perfusion science in recent years, which have the potential to further improve early graft function and prolong graft survival.