Association of Early Bifurcation of Hepatic Artery With Arterial Injury in Right-Sided Living-Donor Hepatectomy: Retrospective Analysis of 500 Cases.

OBJECTIVE: The aim of this study was 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. SUMMARY BACKGROUND DATA: 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 3-dimensional (3-D) images, its significance is underestimated. METHODS: 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. RESULTS: 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 supraportal RPHA ( P < 0.001). 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. CONCLUSIONS: Early bifurcation of the RHA and the RPHA is frequently encountered and requires caution for RLG/RPSG procurement. Special attention should be paid to supraportal RPHA for RLG procurement.

Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats.

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.

Sequential hypothermic and normothermic perfusion preservation and transplantation of expanded criteria donor livers.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 clearance >60% (perfusate lactate cleared to <4.0 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. CONCLUSION: 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.

Nutrition Support in Liver Transplantation and Postoperative Recovery: The Effects of Vitamin D Level and Vitamin D Supplementation in Liver Transplantation.

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 2014-2019. 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.

Bortezomib Against Refractory Antibody-Mediated Rejection After ABO-Incompatible Living-Donor Liver Transplantation: Dramatic Effect in Acute-Phase?

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 (<256/128). Complete remission of refractory AMR was obtained by just 2 doses of bortezomib. Her liver function has been stable thereafter for over 3 years. This case highlighted the efficacy of bortezomib against refractory AMR after ABOi-LDLT. Unlike previous reports, the efficacy was very dramatic, presumably due to the administration timing near the peak of acute-phase AMR.

A luminance-based heart chip assay for assessing the efficacy of graft preservation solutions in heart transplantation in rats.

OBJECTIVE: We developed a novel luciferase-based viability assay for assessing the viability of hearts preserved in different solutions. We examined whether this in vitro system could predict heart damage and survival after transplantation in rats. DESIGN: By our novel system, preserved heart viability evaluation and transplanted heart-graft functional research study. SETTING: University basic science laboratory. INTERVENTIONS: Isolated Luciferase-transgenic Lewis (LEW) rat cardiac-tissue-chips were plated on 96-well tissue-culture plates and incubated in preservation solutions at 4°C. Viability was measured as photon intensity by using a bio-imaging system. Heart-grafts preserved in University of Wisconsin (UW), extracellular-trehalose-Kyoto (ETK), Euro-Collins (EC), histidin-tryptophan-ketoglutarat solution (HTK), lactated Ringer's (LR) or normal saline solution were transplanted cervically by using a cuff-technique or into the abdomens of syngeneic wild-type LEW rats by using conventional microsurgical suture techniques. MAIN OUTCOME MEASURES: Imaging an evaluation of preservation heart-graft and functional analysis. RESULTS: Cardiac-tissue-chips preserved with UW, HTK or ETK solution gave higher luminance than those preserved with EC, LR or normal saline (p<0.03). After 24 h of preservation of hearts in each solution at 4°C, the beating of the isolated hearts was evaluated. The success rate, evaluation of beating, of cervical heart transplants using UW and ETK solution exceeded 70%, but those using other preservation solutions were lower (UW: 100%, ETK: 75%, EC: 42.86%, HTK: 14.29%, normal saline: 0%). Histological analysis of cervical heart-grafts after 3 h preservation by myeloperoxidase (MPO), zona occludens-1(ZO-1), and caspase-3 immunostaining revealed different degrees of preservation damage in all grafts. CONCLUSIONS: Our novel assay system is simple and can test multiple solutions. It should therefore be a powerful tool for developing and improving new heart-graft preservation solutions.

Use of Mesenchymal Stem Cell-Conditioned Medium to Activate Islets in Preservation Solution.

Pancreatic islet transplantation has received widespread attention as a promising treatment for type 1 diabetes. However, islets for transplantation are subject to damage from a number of sources, including ischemic injury during removal and delivery of the donor pancreas, enzymatic digestion during islet isolation, and reperfusion injury after transplantation in the recipient. Here we found that protein fractions secreted by mesenchymal stem cells (MSCs) were capable of activating preserved islets. A conditioned medium from the supernatant obtained by culturing adipose tissue MSCs (derived from wild-type Lewis rats) was prepared for 2 days in serum-free medium. Luc-Tg rat islets to which an organ preservation solution was added were then incubated at 4°C with fractions of various molecular weights prepared from the conditioned medium. Under the treatment with some of the fractions, by 4 days the relative luminescence intensities (representative of the ATP levels of the cold-preserved islets) had increased to over 150% of their initial values. Our novel system may be able to restore isolated islets to the condition they were in before transport, culture, and transplantation.