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The purpose of this study was to assess the safety and feasibility of sequential hypothermic oxygenated perfusion and normothermic machine perfusion and the potential benefits of graft viability preservation and assessment before liver transplantation.With the Food and Drug Administration and institutional review board approval, 17 expanded criteria donor livers underwent sequential hypothermic oxygenated perfusion and normothermic machine perfusion using our institutionally developed perfusion device.Expanded criteria donor livers were from older donors, donors after cardiac death, with steatosis, hypertransaminasemia, or calcified arteries. Perfusion duration ranged between 1 and 2 hours for the hypothermic oxygenated perfusion phase and between 4 and 9 hours for the normothermic machine perfusion phase. Three livers were judged to be untransplantable during normothermic machine perfusion based on perfusate lactate, bile production, and macro-appearance. One liver was not transplanted because of recipient issue after anesthesia induction and failed reallocation. Thirteen livers were transplanted, including 9 donors after cardiac death livers (donor warm ischemia time 16-25 minutes) and 4 from donors after brain death. All livers had the standardized lactate clearance60% (perfusate lactate cleared to4.0 mmol/L) within 3 hours of normothermic machine perfusion. Bile production rate was 0.2 to 10.7 mL/h for donors after brain death livers and 0.3 to 6.1 mL/h for donors after cardiac death livers. After transplantation, 5 cases had early allograft dysfunction (3 donors after cardiac death and 2 donors after brain death livers). No graft failure or patient death has occurred during follow-up time of 6 to 13 months. Two livers developed ischemic cholangiopathy. Compared with our previous normothermic machine perfusion study, the bile duct had fewer inflammatory cells in histology, but the post-transplant outcomes had no difference.Sequential hypothermic oxygenated perfusion and normothermic machine perfusion preservation is safe and feasible and has the potential benefits of preserving and evaluating expanded criteria donor livers.

To explore the incidence of early bifurcation of the right hepatic artery (RHA) and the right posterior hepatic artery (RPHA), which is crucial in right lobe graft (RLG) and right posterior sector graft (RPSG) procurement for living-donor liver transplantation.Early bifurcation of the hepatic artery tends to induce oversight of one of the bifurcated arteries and its injury in RLG/RPSG procurement. Unrecognizable on conventional three-dimensional (3-D) images, its significance is underestimated.We enrolled 500 patients who underwent preoperative imaging for scheduled surgeries at two major transplant centers. All-in-one 3-D images consisting of the hepatic artery, portal vein, and bile duct were constructed. Early bifurcation of the RHA and the RPHA was defined as the arteries bifurcating proximal to the cutting line of the right hepatic duct and the right posterior duct, respectively.Early bifurcation of the RHA was seen in 11.3% of cases of an infra-portal RPHA and in 46.0% of cases of a supra-portal RPHA (P0.001). Early bifurcation of the RPHA was encountered in 35.3% of cases of an infra-portal RPHA, in no cases of a supra-portal RPHA, and in 100% of cases in which the arteries to segment 6/7 arose individually from the RHA. The overall incidence of early bifurcation was 19.9% for RHA and 43.6% for RPHA.Early bifurcation of the RHA and the RPHA is frequently encountered and requires caution for RLG/RPSG procurement. Special attention should be paid to supra-portal RPHA for RLG procurement.

Vitamin D plays an important role in the arena of liver transplantation. In addition to affecting skeletal health significantly, it also clinically exerts immune-modulatory properties. Vitamin D deficiency is one of the nutritional issues in the perioperative period of liver transplantation (LT). Although vitamin D deficiency is known to contribute to higher incidences of acute cellular rejection (ACR) and graft failure in other solid organ transplantation, such as kidneys and lungs, its role in LT is not well understood. The aim of this study was to investigate the clinical implication of vitamin D deficiency in LT. LT outcomes were reviewed in a retrospective cohort of 528 recipients during 2014&ndash, 2019. In the pre-transplant period, 55% of patients were vitamin-D-deficient. The serum vitamin D level was correlated with the model for end-stage liver disease (MELD-Na) score. Vitamin D deficiency in the post-transplant period was associated with lower survival after LT, and the post-transplant supplementation of vitamin D was associated with a lower risk of ACR. The optimal vitamin D status and vitamin D supplementation in the post-transplant period may prolong survival and reduce ACR incidence.

Background:It was demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration in the liver. An optimal protocol of polyamine treatment remains unknown in the clinical setting. We examined 2 types of administration methods using rat models. Methods: Experiment 1: evaluation of pharmacokinetics of polyamines. Experiment 2: for 3 days preoperatively and 5 days postoperatively, polyamines were given to male Lewis rats in the following three groups: the control group, no polyamine administration; the chow group, 0.05% polyamines mixed in chow; the bolus group, polyamines (200 μmol/kg) given by gastric tube once a day. All rats received 70% hepatectomy after 40 min of warm IRI. Postoperatively, IRI and regeneration were evaluated with assessment of serum levels of hepatic enzymes, histology and immunohistochemistry of liver tissue, and measurement of remnant liver weight. Results: The blood concentrations of polyamines in the portal vein increased at 1 h of bolus administration, while they did not increase without the bolus. The bolus group was significantly associated with lower serum levels of aspartate/alanine aminotransferases (p < 0.05), decreased hepatocyte congestion, vacuolization and necrosis in histopathological scoring (p < 0.05), a lower number of TUNEL-positive hepatocytes (p < 0.05), higher remnant liver weight at 24, 48, and 168 h (p < 0.05), and a higher Ki-67 labeling index (24 h, p < 0.01) compared with the chow group. Conclusion: The bolus administration of polyamines was more effective in ameliorating IRI and promoting regeneration than chow administration. Perioperative bolus administration of polyamines might be an optimal treatment, when clinically applied.

Antibody-mediated rejection (AMR) is a refractory rejection after donor-specific antibody-positive or ABO blood-type incompatible (ABOi) organ transplantation. Rituximab dramatically improved the outcome of ABOi living-donor liver transplantation (LDLT); however, an effective treatment for posttransplant AMR, once occurred, is yet to be established. A 44-year-old woman with biliary cirrhosis underwent ABOi-LDLT from her sister (AB-to-A). Pretransplant rituximab diminished CD19/20-positive B lymphocytes to 0.6%/0.0%; however, AMR occurred on posttransplant day-6 with marked increase in both CD19/20 cells (17.1%/5.8%) and anti-B IgM/G-titers (1024/512). Despite rituximab readministration, steroid-pulse, intravenous immunoglobulin, and plasmapheresis, AMR was uncontrollable, with further increasing CD19/20 cells (23.0%/0.0%) and antibody-titers (2048/512). Bortezomib (1.0 mg/m2) was thus administered on posttransplant day-9, immediately ameliorating CD19/20 cells (1.3%/0.0%) and antibody-titers (

Introduction: Mesenchymal stem cells (MSCs) are used in various clinical settings for effective cell therapy by taking advantage of their immunomodulatory, regenerative, and anti-inflammatory properties. We previously investigated the effects of the regenerative and anti-inflammatory properties of MSCs for consideration of their clinical application in organ transplantation. Since immunosuppressant agents are administered in nearly all clinical cases of organ transplantation, clarification of the immunological interaction between MSCs and the calcineurin inhibitor tacrolimus (TAC) is needed.Aim: Due to potential use of MSCs in organ transplantation, we assessed immunological interactions between TAC and MSCs in vivo.Methods: Adipose tissue-derived MSCs (AT-MSCs) were obtained from wild-type Lewis rats. We then used a rat heart transplantation model to observe the immunosuppressive effects of AT-MSCs, TAC, and those in combination. Following allogeneic heterotopic heart transplantation from ACI rats to Lewis rats, graft survival was assessed in groups treated with AT-MSCs, TAC, both, or neither.Results: Median survival of the allograft was 14.5 days in the TAC-alone group and 11 days in the MSC+TAC group. Although the difference between those groups was not significant, the survival periods of both were significantly longer as compared to that of the control (median survival =5 days, P