Association between sarcopenia and mortality in cirrhosis is well recognised; however, little is known about the clinical implications of adipose tissue radiodensity, indicative of biological features. This study aimed to determine an association between high subcutaneous adipose tissue (SAT) radiodensity and survival, compare the prevalence of high SAT radiodensity between healthy population and patients with cirrhosis, and identify an association between computed tomography (CT)-measured SAT radiodensity and histological characteristics. Adult patients with cirrhosis (n = 786) and healthy donors (n = 129) with CT images taken as part of the liver transplant (LT) assessment were included. Abdominal SAT biopsies (1–2 g) were harvested from the incision site at the time of LT from 12 patients with cirrhosis. The majority of patients were male (67%) with a mean model for end-stage liver disease (MELD) score of 15 ± 8. SAT radiodensity above -83 HU in females (sub-distribution hazard ratio [sHR] 1.84, 95% CI 1.20–2.85, p = 0.006) and higher than -74 HU in males (sHR 1.51, 95% CI 1.05–1.18, p = 0.02) was associated with the highest mortality risk after adjusting for confounders in competing risk analysis. The frequency of high SAT radiodensity was 26% for those with cirrhosis, compared with 2% in healthy donors (p <0.001). An inverse correlation was found between SAT radiodensity and the mean cross-sectional area of SAT adipocytes (r = -0.67, p = 0.02). Shrunken, smaller adipocytes with expanded interstitial space were predominant in patients with high SAT radiodensity, whereas larger adipocytes with a thin rim of cytoplasm were observed in patients with low SAT radiodensity (744 ± 400 vs. 1,521 ± 1,035 μm², p <0.001). High SAT radiodensity frequently presents and is associated with a higher mortality in cirrhosis. SAT morphological rearrangement in patients with high SAT radiodensity might indicate diminished lipid stores and alterations in tissue characteristics. Poor quality of subcutaneous adipose tissue (fat under the skin) is associated with higher mortality in patients with end-stage liver disease. Fat cells are smaller in patients with poor adipose tissue quality.

Normothermic machine perfusion (NMP) has emerged as a valuable tool in the preservation of liver allografts before transplantation. Randomized trials have shown that replacing static cold storage (SCS) with NMP reduces allograft injury and improves graft utilization. The University of Alberta's liver transplant program was one of the early adopters of NMP in North America. Herein, we describe our seven-year experience applying NMP to extend preservation time in liver transplantation using a 'back-to-base' approach. From 2015 to 2021, 79 livers were transplanted following NMP compared to 386 after SCS only. NMP livers were preserved for a median time of 847min compared to 288.5min in the SCS cohort (p<0.0001). Despite this, we observed significantly improved 30-day graft survival (p=0.030), though no differences in long term patient survival, major complications or biliary or vascular complications. We also found that while SCS time was strongly associated with increased graft failure at one year in the SCS cohort (p=0.006), there was no such association amongst NMP livers (p=0.171). Our experience suggests that NMP can safely extend the total preservation time of liver allografts without increasing complications.

In solid organ transplantation, HLA matching between donor and recipient is associated with superior outcomes. In islet transplantation, an intervention for Type 1 diabetes, HLA matching between donor and recipient is not performed as part of allocation. Susceptibility to Type 1 diabetes is associated with the presence of certain HLA types. This study was conducted to determine the impact of these susceptibility antigens on islet allograft survival. This is a single-centre retrospective cohort study. This cohort of transplant recipients (n = 268) received islets from 661 donor pancreases between March 11th, 1999 and August 29th, 2018 at the University of Alberta Hospital (Edmonton, AB, Canada). The frequency of the Type 1 diabetes susceptibility HLA antigens (HLA-A24, -B39, -DQ8, -DQ2 and–DQ2-DQA1∗05) in recipients and donors were determined. Recipient and donor HLA antigens were examined in relation to time to first C-peptide negative status/graft failure or last observation point. Taking into account multiple transplants per patient, we fitted a Gaussian frailty survival analysis model with baseline hazard function stratified by transplant number, adjusted for cumulative islet dose and other confounders. Across all transplants recipients of donors positive for HLA-DQ8 had significantly better graft survival (adjusted HRs 0.33 95% CI 0.17–0.66; p = 0.002). At first transplant only, donors positive for HLA-DQ2-DQA1∗05 had inferior graft survival (adjusted HR 1.96 95% CI 1.10–3.46); p = 0.02), although this was not significant in the frailty analysis taking multiple transplants into account (adjusted HR 1.46 95% CI 0.77–2.78; p = 0.25). Other HLA antigens were not associated with graft survival after adjustment for confounders. Our findings suggest islet transplantation from HLA-DQ8 donors is associated with superior graft outcomes. A donor positive for HLA-DQ2-DQA1∗05 at first transplant was associated with inferior graft survival but not when taking into account multiple transplants per recipient. The relevance of HLA-antigens on organ allocation needs further evaluation and inclusion in islet transplant registries and additional observational and interventional studies to evaluate the role of HLA-DQ8 in islet graft survival are required. None.

Zofia Czarnecka, Kevin Verhoeff, David Bigam, Khaled Dajani, James Shapiro, Blaire Anderson. Ann Hepatobiliary Pancreat Surg -0001;0:. https://doi.org/10.14701/ahbps.24-172

Background.: Limited information is available regarding outcomes of islet cell isolation (ICI) and transplantation (ITx) using medical assistance in dying (MAiD) donors. We aimed to assess the feasibility and outcomes of ICI and ITx in MAiD donors. Methods.: ICI and ITx from MAiD were compared with donation after circulatory death (DCD) type III between 2016 and 2023. Differences of isolated islet equivalents (IEQs), numeric viability and other quantitative in vitro metabolic measures were assessed. Results.: Overall, 81 ICIs were available of whom 34 (42%) and 47 (58%) from MAiD and DCD-III, respectively. There were no differences of pancreas and digested tissue weight and islets viability among the 2 groups; however, cold ischemic time was longer in MAiD (11.5 versus 9.1 h; P = 0.021). The IEQ (P < 0.001) and percent trapped (P < 0.001) were higher in the DCD-III; however, MAiD islets demonstrated a higher purity (P = 0.020). Overall, 15 ITx were performed of whom 3 (8.8%) and 12 (25.5%) from MAiD and DCD-III, respectively (P = 0.056). Patients had a median fasting C-peptide of 0.51 ng/mL (interquartile range, 0.30–0.76 nmol/L), with no differences between groups (MAiD = 0.52 versus DCD-III = 0.51; P = 0.718). The median HbA1c was 6.2% (interquartile range, 5.7%–7%) (MAiD = 6.3% versus DCD-III = 6.1%; P = 0.815) and BETA2 scores (MAiD = 7.4 versus DCD-III = 12.8; P = 0.229) did not differ. Conclusions.: ICI from MAiD donor pancreas may be successfully transplanted with comparable outcomes to DCD-III and may be used for research. These results justify additional efforts to consider MAiD as another valuable source of grafts for ITx. Further multicenter studies and larger clinical experience are needed to validate our findings.

Given country-specific variance in legislation, limited information is available regarding outcomes of liver transplantation (LT) using medical assistance in dying (MAiD) donation after circulatory death (DCD type-V) grafts. We compared outcomes following LT using DCD type-V vs. conventional DCD type-III grafts. We reviewed all LTs using DCD-V and DCD-III donors performed across Canadian provinces between 2016 (MAiD legalization) and 2023. Primary outcomes were patient and graft survival at 1, 3, and 5 years. Secondary outcomes included early allograft dysfunction, length of stay, postoperative complications, and biliary complications. Among 313 recipients, 56 (17.9%) received DCD-V and 257 (82.1%) DCD-III grafts. DCD-V donors were older (56 vs. 38 years, p <0.0001), and had similar warm ischemic time (20 vs. 23 min, p = 0.190). Patient survival for DCD-V was 89.3%, 85.7%, and 85.7% at 1, 3, and 5 years, with graft survival of 82.1%, 78.6%, and 78.6%, comparable to DCD-III. DCD-V was not associated with graft loss (odds ratio 1.64; 95% CI 0.66-4.08), which was confirmed by multivariable Cox regression analysis (hazard ratio 1.53; 95% CI 0.74-3.15). Early allograft dysfunction occurred more frequently with DCD-III (57.5% vs. 42.9%, p = 0.047), whereas length of stay was longer with DCD-V (21.5 vs. 15 days, p = 0.011). Overall complication rates were similar; biliary complications were more common in DCD-V, but this was not statistically significant (32.1% vs. 23.1%, p = 0.153). Liver grafts from MAiD donors provide outcomes comparable to DCD-III and increased Canadian DCD activity by 21.8%. These findings support MAiD as a valuable additional source of liver grafts, though larger studies are needed to validate long-term safety and efficacy. Liver transplantation using grafts from donors following medical assistance in dying (MAiD) achieves satisfactory patient and graft survival, with complication rates comparable to those following conventional donation after circularly death. MAiD donation increased donation after circularly death liver transplant activity in Canada by 21.8% over 7 years. These findings support MAiD as a valuable additional source of grafts, while also honoring the wishes of patients who choose to donate their organs.