Donation after circulatory death liver transplantation: An in-depth analysis and propensity score-matched comparison.

BACKGROUND: Careful donor-recipient matching and reduced ischemia times have improved outcomes following donation after circulatory death (DCD) liver transplantation (LT). This study examines a single-center experience with DCD LT including high-acuity and hospitalized recipients. METHODS: DCD LT outcomes were compared to a propensity score-matched (PSM) donation after brain death (DBD) LT cohort (1:4); 32 DCD LT patients and 128 PSM DBD LT patients transplanted from 2008 to 2018 were included. Analyses included Kaplan-Meier estimates and Cox proportional hazards models examining patient and graft survival. RESULTS: Median MELD score in the DCD LT cohort was 22, with median MELD of 27 for DCD LT recipients with decompensated cirrhosis. No difference in mortality or graft loss was found (p < .05) between DCD LT and PSM DBD LT at 3 years post-transplant, nor was DCD an independent risk factor for patient or graft survival. Post-LT severe acute kidney injury was similar in both groups. Ischemic-type biliary lesions (ITBL) occurred in 6.3% (n = 2) of DCD LT recipients, resulting in 1 graft loss and 1 death. CONCLUSION: This study supports that DCD LT outcomes can be similar to DBD LT, with a low rate of ITBL, in a cohort including high-acuity recipients. Strict donor selection criteria, ischemia time minimization, and avoiding futile donor/recipient combinations are essential considerations.

Pre-transplant utilization of sorafenib is not associated with increased complications after liver transplantation.

Hepatocellular carcinoma (HCC) is increasing in incidence, resulting in approximately 35% of orthotopic liver transplantation (OLT) performed each year. Sorafenib (SOR) is a multi-kinase inhibitor that is approved for the treatment of unresectable HCC. Concerns have been raised regarding the safety of SOR in patients undergoing major surgery. We retrospectively reviewed 79 consecutive patients with HCC receiving OLT. Patient data were compared for those who received SOR pre-OLT with those who did not. SOR was continued until time of transplant. During this time period, 15 patients received SOR pre-OLT and 64 did not. The two groups were similar with regards to demographic and clinical data. SOR patients were more likely to have larger tumors, more tumor nodules, and be outside of Milan criteria. The rate of recurrence of HCC was not different between the groups (13% in SOR group, 11% in no-SOR group). Surgical complications were not increased in patients receiving SOR prior to OLT. Survival rate was also similar between the two groups (median follow-up 19.7 months). In this small cohort of patients, use of SOR prior to liver transplantation does not confer an increased risk of surgical complications, even when continued until the day of surgery.

Co-expression of vascular endothelial growth factor and interleukin-1 receptor antagonist improves human islet survival and function.

PURPOSE: Ex vivo gene therapy approaches can improve the outcome of islet transplantation for treating type I diabetes. We have previously shown the improvement in islet function and vascularization following ex vivo transfection for human vascular endothelial growth factor (hVEGF) gene expression. In this study, we tested the hypothesis that co-expression of two genes, which target different challenges faced by islets post-transplantation, supplement each other to improve the survival and function of islets. We determined whether there is an additive effect of hVEGF and human interleukin-1 receptor antagonist (hIL-1Ra) gene expression in human islets. MATERIALS AND METHODS: Human islets were co-infected with adenoviral vectors encoding hVEGF and hIL-1Ra. Islets were then incubated with a cocktail of inflammatory cytokines (IL-1beta+TNFalpha+IFNgamma), and islet viability and function were determined. In vivo function was evaluated by transplanting islets under the kidney capsules of streptozotocin-induced non-obese diabetic severe combined immunodeficient (NOD-SCID) mice. RESULTS: Infection of human islets with Adv-hVEGF and/or Adv-hIL-1Ra inhibited expression of inducible nitric oxide synthase (iNOS), decreased the production of nitric oxide (NO), and prevented the loss of in vitro glucose-stimulated insulin response and viability. Moreover, co-expression of hVEGF and hIL-1Ra reduced the blood glucose level of mice, and increased the level of blood insulin and c-peptide upon glucose challenge. CONCLUSIONS: Our results indicated that co-expression of genes that target different insults to transplanted islets can improve the outcome of islet transplantation better than either gene alone.

Glucose stimulation of cytochrome C reduction and oxygen consumption as assessment of human islet quality.

BACKGROUND: An in vitro method to assess human islets could prevent transplantation of nonviable islets and facilitate the optimization of islet preparation. We hypothesize that glucose-stimulated cytochrome c reduction and oxygen consumption by human islets can be used as predictors of transplant success. METHODS: Isolated human islets were obtained from research-grade pancreata. Using a previously developed islet flow culture system, the response of cytochrome c reduction and oxygen consumption to glucose was compared to the ability of islets transplanted into nondiabetic NOD-SCID mice to secrete C-peptide in response to a glucose tolerance test conducted 7 days following transplant (n=10). RESULTS: In vitro responses by human islets were qualitatively similar to those seen in rat islets: glucose increased both oxygen consumption and cytochrome c reduction. However, the responses were smaller in magnitude and quite variable. Scatter plots of C-peptide and quantiles for ln(C-peptide) indicated that 12 ng/ml could be used as threshold of transplant success with which to evaluate the diagnostic potential of cytochrome c and oxygen consumption. Data was analyzed by generating receiver operating curves and the area under the curve was 0.889 (95% CI: 0.645-1.000) and 0.738 (95% CI: 0.413-1.000) for cytochrome c reduction and oxygen consumption respectively (1 indicates absolute predictive capability and 0.5 indicates no predictive capability). CONCLUSIONS: The detection of glucose-stimulated cytochrome c reduction and oxygen consumption may have utility as criteria for the assessment of human islet quality.