Efficiency of leukocyte depletion filters and micro-aggregate filters following intra-operative cell salvage during cesarean delivery.

BACKGROUND: Intra-operative cell salvage is not routinely used during cesarean delivery because it is not cost-effective for patients at low risk of hemorrhage and there are theoretical concerns about amniotic fluid embolism. Some guidelines recommend using leukocyte depletion filters to decrease the risk of amniotic fluid embolism before re-infusing salvaged blood, but these filters are not available in Japan. We compared the efficacy and safety of leukocyte depletion and micro-aggregate filters in combination with intra-operative cell salvage during cesarean delivery. METHODS: Blood was collected in a Cell Saver 5 reservoir during cesarean delivery. Four samples were collected: pre-wash, post-wash, post-filtration with a leukocyte depletion filter and post-filtration with a micro-aggregate filter. Each sample was analyzed for amniotic fluid markers of zinc coproporphyrin-1 and sialyl-Tn, for fetal hemoglobin, and the sample underwent pathological examination for white blood cells and squamous cells. Post-filtration samples were compared using paired t-tests with P <0.05 indicating statistical significance. RESULTS: Zinc coproporphyrin-1 and sialyl-Tn were negative at almost all sample points. Squamous cells decreased by 59.1% post-wash and 91.2% post-filtration using a leukocyte depletion filter. Leukocyte depletion filters removed 99.7% of white blood cells and were more effective in removing white blood cells than micro-aggregate filters (P=0.02). CONCLUSION: Leucocyte depletion filters are more effective in removing white blood cells and squamous cells than micro-aggregate filters, and their introduction for intra-operative cell salvage during cesarean delivery should be considered in Japanese clinical practice.

Mild to Moderate Intrapulmonary Shunting in Pediatric Liver Transplantation: Is Screening Necessary?

BACKGROUND: Despite reported associations between intrapulmonary vascular shunting (IPVS) and morbidity and mortality in pediatric liver transplantation (LT), there are no guidelines for screening. OBJECTIVE: To investigate IPVS before and after pediatric LT. METHODS: Retrospective records review of all pediatric LT (n = 370) from 2005 to 2015 at a single institute in Japan. All children with cirrhosis and clinical suspicion of IPVS without cardiac or pulmonary conditions were included. 99mTechnetium labelled macroaggregated albumin (99mTcMAA) scans were performed before and after LT. The severity of IPVS was graded using shunt ratios. RESULTS: Twenty-four children fulfilled inclusion criteria and underwent Tc99MAA scans. All revealed mild (<20%) to moderate (20%-40%) grades of IPVS. Following LT, the mean shunt ratio regressed from 20.69 ± 6.26% to 15.1 ± 3.4% (P = .06). The median (range) follow-up was 17 (4-85) months. Mortality was zero. The incidence of portal vein thrombosis (4.2%) biliary strictures (12.5%) and graft loss (4.1%) in the study group was not statistically significant compared to the remainder of the 370 transplants (3.2%, 9.4% and 3%, respectively). Sub-group analysis revealed hepatopulmonary syndrome (HPS) in 2 out of 24 children. The mean shunt ratios before and after LT were 39.2 ± 0.77% and 16.2 ± 8.5%, respectively (P = .08). There was 1 complication (intra-abdominal abscess). CONCLUSIONS: HPS is less likely in mild to moderate IPVS. LT may achieve comparable results when performed in the presence of mild to moderate IPVS.

Six National University Consortium in Liver Transplant Professionals Training (SNUC-LT) Program in Japan.

BACKGROUND: There has been no public structured training program for transplant surgeons in Japan. However, such a program is crucial for optimizing liver transplant surgery and training young professionals in liver transplant surgery. A comprehensive training program was recently developed and the underlying concepts, structure and curriculum, and results of this program are described here. METHODS: We developed a 3-year training program in 2014 called the Six National University Consortium in Liver Transplant Professionals Training (SNUC-LT) program supported by the Ministry of Education, Culture, Sports, Science, and Technology. This program is based on strong cooperation among 6 national universities (Kumamoto, Okayama, Nagasaki, Kanazawa, Niigata, and Chiba Universities). The program includes various courses to help trainees learn transplant theory and practice as well as to teach surgical skills required to safely perform transplant surgery. RESULTS: Three trainees completed the specially designed 3-year curriculum. They attended lectures on transplant theory for an average of 59 hours and participated in an average of 44 liver transplant surgeries and 51 liver resections for transplant practice. Trainees from low-volume centers had sufficient opportunities to attend operations in high-volume centers because of the cooperative agreement among the universities. After finishing the program, the trainees were certified as talent-proven liver transplant surgeons. CONCLUSIONS: The SNUC-LT program is the first national program in Japan to have strong professional support. Our multicenter program enables young surgeons to have more abundant knowledge, more extensive experience, better surgical skills, and smoother communication skills in the field of liver transplantation.

Liver Transplantation for Mitochondrial Respiratory Chain Disorder: A Single-Center Experience and Excellent Marker of Differential Diagnosis.

Mitochondrial respiratory chain disorder (MRCD) can cause liver failure requiring liver transplantation (LT), although it is often difficult to diagnose before LT. From 2005 to 2016, 9 MRCD patients with the median age at LT of 6 months underwent LT in our institute. Their clinical courses were retrospectively reviewed and the laboratory parameters were compared between the MRCD patients and 10 patients with acute liver failure unrelated to MRCD (non-MRCD). Five patients had extrahepatic manifestations, including developmental disorders in 3 and failure to thrive in 3, before LT. Only 3 patients (33.3%) were diagnosed before LT. Between MRCD and non-MRCD, lactate was significantly high and lactate-to-pyruvate ratio (L/P ratio) tended to be higher in MRCD. From the receiver operating characteristic curve, the optimal cutoff value of lactate was 50.0 mg/dL and that of L/P ratio was 23.2. Patient survival rate of MRCD was 77.8%, although 2 patients with mitochondrial depletion syndrome suffered from de novo pulmonary hypertension after LT. Our experiences showed the difficulty of preoperative diagnosis, and preoperative extrahepatic manifestations did not always mean poor outcome. Our study showed that lactate value and L/P ratio can be excellent predictors of MRCD.

Total internal biliary diversion during liver transplantation for type 1 progressive familial intrahepatic cholestasis: a novel approach.

LT for PFIC type 1 is often complicated by postoperative diarrhea and recurrent graft steatosis. A 26-month-old female child with cholestatic jaundice, pruritus, diarrhea, and growth retardation revealed total bilirubin 9.1 mg/dL, gamma-glutamyl transpeptidase 64 IU/L, and TBA 295.8 µmol/L. Genetic analysis confirmed ATP8B1 defects. A LT (segment 2, 3 graft) from the heterozygous father was performed. Biliary diversion was performed by a 35-cm jejunum conduit between the graft hepatic duct and the mid-transverse colon. Stools became pigmented immediately. Follow-up at 138 days revealed resolution of jaundice and pruritus and soft-to-hard stools (6-8 daily). Radioisotope hepato-biliary scintigraphy (days 26, 68, and 139) confirmed unobstructed bile drainage into the colon (t1/2 34, 27, and 19 minutes, respectively). Contrast meal follow-through at day 62 confirmed the absence of any colo-jejuno-hepatic reflux. At 140 days, contrast follow-through via the biliary stent revealed patent jejuno-colonic anastomosis and satisfactory transit. Graft biopsy at LT, 138 days, and 9 months follow-up revealed comparable grades of macrovesicular steatosis (<20%). TIBD during LT may be a clinically effective stoma-free biliary diversion and may prevent recurrent graft steatosis following LT for PFIC type 1.

Continuous postoperative pain control using a multiple-hole catheter after iliac bone grafting: comparison between ropivacaine and levobupivacaine.

The aim of this study was to compare the analgesic effects of ropivacaine and levobupivacaine in continuous infiltration anaesthesia delivered via a multiple-hole catheter for the purpose of postoperative analgesia after iliac bone grafting. Thirty-four patients scheduled for iliac bone grafting in the maxillofacial region participated in this study. The patients were randomized to a ropivacaine group (Ropi group) and a levobupivacaine group (Levo group). After harvesting the iliac bone for grafting, a multiple-hole catheter was placed on the periosteum of the iliac bone. When surgery was completed, continuous administration was started at 4 ml/h of 0.2% ropivacaine (Ropi group) or 0.25% levobupivacaine (Levo group). Pain was evaluated in the recovery room and at 4h after surgery, as well as at 9:00 and 18:00 on postoperative days 1, 2, and 3, using a visual analogue scale. Side effects were also recorded. No significant difference in the visual analogue scale scores at rest or in motion was observed between the two groups. In addition, there were no side effects in the two groups. Both 0.2% ropivacaine and 0.25% levobupivacaine provided comparable analgesic effects in continuous infiltration anaesthesia delivered via a multiple-hole catheter after iliac bone grafting.

High rate of vaccine failure after administration of acellular pertussis vaccine pre- and post-liver transplantation in children at a children's hospital in Japan.

We assessed the serological response to pertussis vaccines administered pre- and post-liver transplantation in 58 pediatric patients at a children's hospital in Japan. A high rate of pertussis vaccine failure was observed, 44.8% against the pertussis toxin and 69.0% against filamentous hemagglutinin, with no difference in the seropositivity rate with respect to the timing of the vaccination during the peritransplant period.

Hepatic arterial complications in adult living donor liver transplant recipients: a single-center experience of 673 cases.

BACKGROUND: Hepatic arterial reconstruction during living donor liver transplantation (LDLT) is a very delicate and technically complicated procedure. Post-LDLT hepatic arterial complications are associated with significant morbidity and mortality. METHODS: We retrospectively analyzed the details of post-operative hepatic arterial complications in 673 consecutive adult LDLT recipients between January 1996 and September 2009. RESULTS: Hepatic arterial complications occurred in 43 of 673 adult recipients (6.4%) within a median of 13 post-transplant days (range, 1-63). These included hepatic artery thrombosis (including anastomotic stenosis) in 33 cases, anastomotic bleeding in seven cases, and rupture of anastomotic aneurysm in three cases. To treat these complications, surgical re-anastomosis was performed in 26 cases, while the other 17 cases underwent conservative therapies, including four angioplasties by interventional radiology. Biliary complications after hepatic arterial complications occurred in 17 cases. The overall survival rate after LDLT was significantly lower in the hepatic arterial complication group compared with that in the non-complication group (60.7% vs. 80.1% at one yr, 44.3% vs. 74.2% at five yr, respectively; p < 0.001). Multivariate analysis showed that the extra-anatomical anastomosis (p = 0.011) was the only independent risk factor for hepatic arterial complications. CONCLUSION: Because hepatic arterial complications after LDLT are associated with poor patient survival, early diagnosis and immediate treatment are crucial. The anatomical anastomosis may be the first choice for the hepatic arterial reconstruction to the extent possible.

Clinical outcomes and evaluation of the quality of life of living donors for pediatric liver transplantation: a single-center analysis of 100 donors.

There are few reports about the quality of life (QOL) and morbidities of pediatric living donor liver transplantation (LDLT) donors. We evaluated the potential morbidities and identified the predictive factors regarding the QOL of living donors after pediatric LDLT. This cross-sectional study was a single-center analysis of 100 donors for pediatric LDLT. The severity of morbidities was assessed with the Clavien classification, the QOL was investigated with the short form-36 (SF-36), and the decision-making process regarding donation was analyzed with questionnaires. The median follow-up period was 3.8 years (range, 2.2-6.0 years). A total of 13% of the donors developed postoperative complications of Clavien grades I (7%), II (3%), and IIIA (3%). There was no grade IV morbidity or mortality. Eighty-one donors responded to the questionnaire and SF-36. The analysis of the questionnaires revealed that the donors had difficulty in the decision-making process, and suggested that it may be necessary to administer multistep informed consent. We identified unique predictive risk factors for lower SF-36 scores in the donors, which were the time to donation (more than 4 weeks) and the predonation self-oriented perception. The donors who have risk factors require enhanced pre- and post-donation psychological care.

Impact of rituximab desensitization on blood-type-incompatible adult living donor liver transplantation: a Japanese multicenter study.

We evaluated the effects of rituximab prophylaxis on outcomes of ABO-blood-type-incompatible living donor liver transplantation (ABO-I LDLT) in 381 adult patients in the Japanese registry of ABO-I LDLT. Patients underwent dual or triple immunosuppression with or without B cell desensitization therapies such as plasmapheresis, splenectomy, local infusion, intravenous immunoglobulin and rituximab. Era before 2005, intensive care unit-bound status, high Model for End-Stage Liver Disease score and absence of rituximab prophylaxis were significant risk factors for overall survival and antibody-mediated rejection (AMR) in the univariate analysis. After adjustment for era effects in the multivariate analysis, only absence of rituximab prophylaxis was a significant risk factor for AMR, and there were no significant risk factors for survival. Rituximab prophylaxis significantly decreased the incidence of AMR, especially hepatic necrosis (p < 0.001). In the rituximab group, other B cell desensitization therapies had no add-on effects. Multiple or large rituximab doses significantly increased the incidence of infection, and early administration had no advantage. In conclusion, outcomes in adult ABO-I LDLT have significantly improved in the latest era coincident with the introduction of rituximab.

Clinical decision-making augmented by simulation training: neural correlates demonstrated by functional imaging: a pilot study.

BACKGROUND: Investigation of the neuroanatomical basis of clinical decision-making, and whether this differs when students are trained via online training or simulation training, could provide valuable insight into the means by which simulation training might be beneficial. METHODS: The aim of this pilot prospective parallel group cohort study was to investigate the neural correlates of clinical decision-making, and to determine if simulation as opposed to online training influences these neural correlates. Twelve third-year medical students were randomized into two groups and received simulation-based or online-based training on anaphylaxis. This was followed by functional magnetic resonance imaging scanning to detect brain activation patterns while answering multiple choice questions (MCQs) related to anaphylaxis, and unrelated non-clinical (control) questions. Performance in the MCQs, salivary cortisol levels, heart rate, and arterial pressure were also measured. RESULTS: Comparing neural responses to clinical and non-clinical questions (in all participants), significant areas of activation were seen in the ventral anterior cingulate cortex and medial prefrontal cortex. These areas were activated in the online group when answering action-based questions related to their training, but not in the simulation group. The simulation group tended to react more quickly and accurately to clinical MCQs than the online group, but statistical significance was not reached. CONCLUSIONS: The activation areas seen could indicate increased stress when answering clinical questions compared with general non-clinical questions, and in the online group when answering action-based clinical questions. These findings suggest simulation training attenuates neural responses related to stress when making clinical decisions.

Impact of rewarming preservation by continuous machine perfusion: improved post-transplant recovery in pigs.

BACKGROUND: Utilization of grafts from donors after cardiac death (DCD) greatly expands the organ pool. However, implementation of such a strategy requires the development of novel preservation methods to achieve recovery from changes owing to warm ischemia. METHODS: To assess potential methods, porcine livers harvested after 60 minutes of warm ischemic time (WIT) were perfused and preserved under the following conditions: Group 1 (n = 3), 2-hour simple cold storage and 2-hour machine perfusion (MP) at 8°C; group 2 (n = 3), 2 hours at 25°C and MP at 25°C and group 3 (n = 3), 2-hour simple cold storage and gradual rewarming to 25°C by MP. The preserved liver grafts were transplanted orthotopically into recipients. RESULTS: The aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and hyaluronic acid (HA) levels in recipient blood at 2 hours after reperfusion were significantly lower among group 3: AST, 789 ± 258.8, 1203 ± 217.0, and 421 ± 55.8 IU/L; LDH, 1417 ± 671.2, 2132 ± 483.9, and 634 ± 263.9 IU/L; and HA, 1660 ± 556.5, 1463 ± 332.3, and 575 ± 239.0 ng/mL for groups 1, 2 and 3, respectively. Histologically, necrosis and swelling of hepatocytes were less severe among group 3 than groups 1 and 2. Group 3 animals showed better vital responses and started spontaneous breathing within 2 hours after reperfusion; 1 recipient survived for >24 hours, although all animals in groups 1 and 2 died within 2 to 3 hours after reperfusion. CONCLUSION: Rewarming by MP preservation may facilitate recovery and resuscitation of DCD liver grafts.

Transgenic pig expressing the red fluorescent protein kusabira-orange as a novel tool for preclinical studies on hepatocyte transplantation.

INTRODUCTION: Research on hepatocyte transplantation as an alternative or supplementary treatment for liver transplantation is progressing. However, to advance to clinical trials, confidence in the technique must be established and its safety must be validated by conducting experiments using animals of comparable sizes to humans, such as pigs. We used transgenic pigs expressing red fluorescence protein for investigating the distribution and survival of transplanted cells. MATERIALS AND METHODS: Donor hepatocytes were isolated from transgenic Kusabira-Orange (KO)-expressing pigs (age, 41 days; weight, 10 kg) created by in vitro fertilization using sperm from a transgenic-cloned KO pig by Matsunari et al. and ova from a domestic pig. The hepatocyte transplant recipients were the nontransgenic, KO-negative littermates. In these recipient pigs, double lumen cannulae were inserted into the supramesenteric veins to access the hepatic portal region. KO-positive donor hepatocytes from the transgenic male pig were isolated using collagenase perfusion. Hepatocytes (1 × 10(9) cells) were transplanted through the cannula. For estimating allogeneic immunogenicity, full-thickness skin (3 × 3 cm) from the same donor was grafted orthotopically on the neck region of the recipients. Immunosuppressive treatment was not implemented. The recipient pigs were humanely killed at 7 and 39 days after transplantation, and the organs were harvested, including the lungs, heart, liver, pancreas, and kidneys. RESULTS: Strong red fluorescence was detected in both the parenchymal and nonparenchymal hepatocytes of the transgenic male donor pig by fluorescent microscopy. Transplanted cells were detected in the liver and lung of the recipient pigs at 7 days after perfusion. Hepatocytes remained in the liver and lung of recipients on day 39, with lower numbers than that on day 7. CONCLUSION: Transgenic pigs expressing the fluorescent protein KO serve as a useful model of cell transplantation in preclinical studies.

Long-term outcomes of pediatric living donor liver transplantation in Japan: an analysis of more than 2200 cases listed in the registry of the Japanese Liver Transplantation Society.

The Japanese Liver Transplantation Society (JLTS) was established in 1980 in order to characterize and follow trends in patient characteristics and graft survival among all liver transplant patients in Japan. This study analyzed the comprehensive factors that may influence the outcomes of pediatric patients who undergo living donor liver transplantation (LDLT) by evaluating the largest cohort in the world. Between November 1989 and December 2010, 2224 pediatric patients underwent LDLT in Japan. There were 998 male (44.9%) and 1226 female donors (55.1%) without donor mortalities related to transplant surgery. There were 946 male (42.5%) and 1278 female (57.5%) recipients with a median age of 4.0 years (range: 13 days to 17.9 years). Cholestatic liver disease was the leading indication for LDLT (n = 1649; 76.2%), followed by metabolic disorders (n = 194; 8.7%), acute liver failure (n = 192; 8.6%) and neoplastic liver disease (n = 66; 3.0%). The 1-, 5-, 10- and 20-year patient survival rates were 88.3%, 85.4%, 82.8% and 79.6%, respectively. Blood-type incompatibility, recipient age, etiology of liver disease and transplant era were found to be significant predictors of overall survival. We are able to achieve satisfactory long-term pediatric patient survival outcomes in the JLTS series without compromising the living donors.

Sex differences in the human brain and the impact of sex chromosomes and sex hormones.

While there has been increasing support for the existence of cerebral sex differences, the mechanisms underlying these differences are unclear. Based on animal data, it has long been believed that sexual differentiation of the brain is primarily linked to organizational effects of fetal testosterone. This view is, however, in question as more recent data show the presence of sex differences before the onset of testosterone production. The present study focuses on the impact that sex chromosomes might have on these differences. Utilizing the inherent differences in sex and X-chromosome dosage among XXY males, XY males, and XX females, comparative voxel-based morphometry was conducted using sex hormones and sex chromosomes as covariates. Sex differences in the cerebellar and precentral gray matter volumes (GMV) were found to be related to X-chromosome dosage, whereas sex differences in the amygdala, the parahippocamus, and the occipital cortex were linked to testosterone levels. An increased number of sex chromosomes was associated with reduced GMV in the amygdala, caudate, and the temporal and insular cortices, with increased parietal GMV and reduced frontotemporal white matter volume. No selective, testosterone independent, effect of the Y-chromosome was detected. Based on these observations, it was hypothesized that programming of the motor cortex and parts of cerebellum is mediated by processes linked to X-escapee genes, which do not have Y-chromosome homologs, and that programming of certain limbic structures involves testosterone and X-chromosome escapee genes with Y-homologs.

Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice.

AIMS/HYPOTHESIS: Hyperlipidaemia is an independent risk factor for the progression of diabetic nephropathy, but its molecular mechanism remains elusive. We investigated in mice how diabetes and hyperlipidaemia cause renal lesions separately and in combination, and the involvement of Toll-like receptor 4 (TLR4) in the process. METHODS: Diabetes was induced in wild-type (WT) and Tlr4 knockout (KO) mice by intraperitoneal injection of streptozotocin (STZ). At 2 weeks after STZ injection, normal diet was substituted with a high-fat diet (HFD). Functional and histological analyses were carried out 6 weeks later. RESULTS: Compared with treatment with STZ or HFD alone, treatment of WT mice with both STZ and HFD markedly aggravated nephropathy, as indicated by an increase in albuminuria, mesangial expansion, infiltration of macrophages and upregulation of pro-inflammatory and extracellular-matrix-associated gene expression in glomeruli. In Tlr4 KO mice, the addition of an HFD to STZ had almost no effects on the variables measured. Production of protein S100 calcium binding protein A8 (calgranulin A; S100A8), a potent ligand for TLR4, was observed in abundance in macrophages infiltrating STZ-HFD WT glomeruli and in glomeruli of diabetic nephropathy patients. High-glucose and fatty acid treatment synergistically upregulated S100a8 gene expression in macrophages from WT mice, but not from KO mice. As putative downstream targets of TLR4, phosphorylation of interferon regulatory factor 3 (IRF3) was enhanced in kidneys of WT mice co-treated with STZ and HFD. CONCLUSIONS/INTERPRETATION: Activation of S100A8/TLR4 signalling was elucidated in an animal model of diabetic glomerular injury accompanied with hyperlipidaemia, which may provide novel therapeutic targets in progressive diabetic nephropathy.

Functional recovery of donation after cardiac death liver graft by continuous machine perfusion preservation in pigs.

INTRODUCTION: Grafts from donation after cardiac death (DCD) will greatly contribute to the expand the donor pool. However, these grafts may require the development of the preservation methods because of primary nonfunction and severe ischemic bile duct injury. METHODS: Porcine livers were perfused with a newly developed machine perfusion (MP) system. Each system for the portal vein or the hepatic artery had a roller pump, a flow meter, and a pressure sensor. The livers were perfused with University of Wisconsin (UW)-gluconate at 4°C-6°C for 3 hours after 2 hours simple cold storage (CS). The portal vein flow rate was 0.5 mL/min/g liver (pressure, 10 mm Hg) and the hepatic artery flow rate was 0.2 mL/min/g liver (pressure, 30 mm Hg). Orthotopic liver transplantation was performed in pigs comparing Group 1 (n = 4) procured after acute hemorrhagic shock preserved by MP, Group 2 (n = 3) procured after warm ischemia time (WIT) of 30 minutes with CS preservation, and Group 3 (n = 4) procured with 30 minutes of WIT and MP preservation. RESULTS: Collected effluent aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in the perfusion solution and serum AST and LDH were significantly lower in Group 1. AST and LDH results were lower in Group 3 than Group 2. Survival rates in Groups 1 and 3 were 3/4, but 0/3 in Group 2. CONCLUSION: MP preservation was a useful promising preservation mode for DCD liver grafts.

Pretransplant screening and evaluation of liver graft viability using machine perfusion preservation in porcine transplantation.

A novel method using machine perfusion for pretransplant screening and evaluation of the viability of liver grafts has been proposed, seeking to prevent severe ischemia-reperfusion injury and to reduce the risk of primary graft nonfunction. This study sought to evaluate the viability of critical grafts, which were obtained from expanded criteria donors or donation after cardiac death donors during preservation with a new machine preservation perfusion system (NES-01). The normalized pressure transition in the hepatic artery was employed as an evaluation index for liver viability. As a result, the normalized pressure (p/p(0)) in the hepatic artery showed a distinctive transition under each experimental conditions controlled by warm ischemic time (WIT). The high viability graft, obtained under the condition of WIT as 0 minutes (WIT0), showed a quick response to hepatic artery pressure after initiating perfusion, whereas the normalized pressure showed a sudden decrease. In contrast, the normalized pressure among WIT60, which may cause the graft to lose viability, showed a poor hepatic artery response. These findings corresponded to the cumulative release of enzymes. The findings of our study suggest that monitoring of the pressure drop rate in the hepatic artery during machine perfusion can be used to evaluate liver graft viability.