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With increasing demand for donor organs for transplantation, machine perfusion (MP) promises to be a beneficial alternative preservation method for donor livers, particularly those considered to be of suboptimal quality, also known as extended criteria donor livers. Over the last decade, numerous studies researching MP of donor livers have been published and incredible advances have been made in both experimental and clinical research in this area. With numerous research groups working on MP, various techniques are being explored, often applying different nomenclature. The objective of this review is to catalog the differences observed in the nomenclature used in the current literature to denote various MP techniques and the manner in which methodology is reported. From this analysis, we propose a standardization of nomenclature on liver MP to maximize consistency and to enable reliable comparison and meta‐analyses of studies. In addition, we propose a standardized set of guidelines for reporting the methodology of future studies on liver MP that will facilitate comparison as well as clinical implementation of liver MP procedures.

Introduction Waiting list mortality is high in patients awaiting liver transplantation (LT). Despite the use of the Model for Endstage Liver Disease (MELD) score, patients with severe hyponatremia have an even worse waiting list survival. We assessed the impact of mild hyponatremia on LT waiting list survival and overall survival. We also aim to identify if there are any patient groups that are underserved in the MELD based allocation system. Methodology Data were collected from 3 transplant centers located in The Netherlands, Germany, and the United States of America. Serum bilirubin, creatinine, sodium, and international normalized ratio (INR) were collected and MELD scores calculated using the standard formula. Mild hyponatremia was defined as serum sodium level of 130-134 mmol/L. Results In total 1658 patients were included in this study. A strong correlation was found between serum sodium and overall and waiting list survival (P < 0.001). Post-LT survival was also significantly decreased in the mild hyponatremia group (P < 0.001). Waiting list survival for patients with serum sodium levels 130-134 mmol/L was worse compared to patients with normal sodium levels in all three centers together and each center individually (P < 0.001). Waiting list and overall survival was significantly worse in the 166 patients with cholestatic liver disease compared to patients with non-cholestatic liver disease (P = 0.041; P = 0.005). Post-LT survival also was significantly worse in this group (P = 0.022). Conclusion Mild hyponatremia is associated with significantly worse waiting list survival in patients awaiting LT. It is also associated with increased post-LT mortality. Patients listed for cholestatic liver disease may be underserved in the current allocation model. Serum sodium should therefore have a more prominent role in liver allocation. [ABSTRACT FROM AUTHOR]

Background: Recent evidence supports the use of machine perfusion technologies (MP) for marginal liver grafts. Their effect on enhanced recovery, however, remains uncertain., Objectives: To identify areas in which MP might contribute to an ERAS program and to provide expert panel recommendations., Data Sources: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central., Methods: Systematic review and meta-analysis following PRISMA guidelines and recommendations using the GRADE approach. CRD42021237713 RESULTS: Both hypothermic (HMP) and normothermic (NMP) machine perfusion demonstrated significant benefits in preventing postreperfusion syndrome (PRS) (HMP OR .33, .15-.75 CI; NMP OR .51, .29-.90 CI) and early allograft dysfunction (EAD) (HMP OR .51, .35-.75 CI; NMP OR .66, .45-.97 CI), while shortening LOS (HMP MD -3.9; NMP MD -12.41). Only NMP showed a significant decrease in the length of ICU stay (L-ICU) (MD -7.07, -8.76; -5.38 CI), while only HMP diminishes the likelihood of major complications. Normothermic regional perfusion (NRP) reduces EAD (OR .52, .38-.70 CI) and primary nonfunction (PNF) (OR .51, .27-.98 CI) without effect on L-ICU and LOS., Conclusions: The use of HMP decreases PRS and EAD, specifically for marginal grafts. This is supported by a shorter LOS and a lower rate of major postoperative complications (QOE; moderate | Recommendation; Strong). NMP reduces the incidence of PRS and EAD with associated shortening in L-ICU for both DBD and DCD grafts (QOE; moderate | Recommendation; High) This technology also shortens the length of hospital stay (QOE; low | Recommendation; Strong). NRP decreases the likelihood of EAD (QOE; moderate) and the risk of PNF (QOE; low) when compared to both DBD and SRR-DCD grafts preserved in SCS. (Recommendation; Strong)., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Dynamic preservation strategies are a promising option to improve graft quality before transplantation, and to extend preservation time for either logistic or treatment reasons. In contrast to normothermic oxygenated perfusion, which intends to mimic physiological conditions in the human body, with subsequent clinical application for up to 24 hrs, hypothermic perfusion is mainly used for a relatively short period with protection of mitochondria and subsequent reduction of oxidative injury upon implantation. The results from two randomized controlled trials, where recruitment has finished are expected this year. Both ex situ perfusion techniques are increasingly applied in clinical transplantation including recent reports on viability assessment, which could open the door for an increased liver utilization in the future., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3-synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3 + CD147 + ), but not single antigen (GPC3 - CD147 + ) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.

Despite the passage of a decade since the tragic loss of an organ recovery team from the University of Michigan, there are currently no national standards governing air and ground transportation of organ recovery personnel. Consequently, the American Society of Transplant Surgeons, the Association of Organ Procurement Organizations, and the United Network for Organ Sharing jointly convened a transportation summit to review and update recommendations for national transportation standards. Expanded air transport quality assurance protocols, including a requirement for two engine turbine-powered aircraft piloted by two qualified pilots certified through onsite inspections was recommended. Ground transportation providers must ensure adequate safety restraints are available, ambulance avoided if possible, and the use of lights and sirens minimized. Finally, adequate insurance coverage for all team members, including trainees should be provided and should not rely on carrier liability insurance policies. The summit participants have committed the support of their organizations to promote and enact these regulations nationally., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Outcomes for adult-to-adult living liver donors (LDs) are largely based on short-term data drawn from single-center studies. The aim of this study was to determine how living liver donation (LLD) impacts self-reported quality-of-life (QOL) up to 6 years after donation in a sample of residents from New York State. New York transplant programs are state-mandated to track LDs as part of a quality assurance and patient safety effort. Donor-reported QOL within 1 year of donation and longitudinal data over a 10-year period were analyzed. Self-reported surveys include the following domains: employment, finances, health/life insurance, activities of daily living, physical/emotional health, donor experience, relationships, and LD opinions. There were 220 LDs in New York (2004-2013) who completed a survey over the 10-year period with many donors completing surveys at several points in time. Overall, longterm LDs remain as comfortable about LLD as they were during the first year after donation (95%). The majority of LDs reported feeling as well as before LLD (72%). At 1 year after donation, 60% of subjects self-reported medical problems, and 30% reported emotional issues. However, the majority reported that they would willingly donate again. In conclusion, LDs remain satisfied with their decision to donate over time. A minority of LDs report longterm medical and emotional issues. The conclusions provide information for educational interventions to improve informed choice to those considering donation., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)

The pervasive shortage of deceased donor liver allografts contributes to significant waitlist mortality despite efforts to increase organ donation. Ex vivo liver perfusion appears to enhance preservation of donor organs, extending viability and potentially evaluating function in organs previously considered too high risk for transplant. These devices pose novel challenges for organ allocation, safety, training, and finances. This white paper describes the American Society of Transplant Surgeons' belief that organ preservation technology is a vital advance, but its use should not change fundamental aspects of organ allocation. Additional data elements need to be collected, made available for organ assessment by transplant professionals to allow determination of organ suitability in the case of reallocation and incorporated into risk adjustment methodology. Finally, further work is needed to determine the optimal strategy for management and oversight of perfused organs prior to transplantation., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Biopsy findings at the time of procurement of deceased donor kidneys remain the most common reason cited for kidney discard. To determine the value of renal allograft histology in predicting outcomes, we evaluated the significance of histologic findings, read by experienced renal pathologists, in 975 postreperfusion biopsy specimens collected from 2005 to 2009 after living donor ( n =427) or deceased donor ( n =548) renal transplant. We evaluated specimens for the degree of glomerulosclerosis, interstitial fibrosis and tubular atrophy, and vascular disease; specimens with a score of 0 or 1 (scale, 0-3) for each parameter were considered optimal. Overall, 66.3% of living donor kidneys and 50.7% of deceased donor kidneys received an optimal histology score ( P <0.001). Irrespective of donor status, suboptimal kidneys came from older donors with a higher incidence of diabetes mellitus, hypertension, and obesity and a higher mean kidney donor risk index (all P <0.001). Death-censored outcomes after transplant differed significantly between optimal and suboptimal kidneys only in the deceased donor transplants ( P =0.02). Regardless of histologic classification, outcomes with deceased donor kidneys were inferior to outcomes with living donor kidneys. However, 73.2% of deceased donor kidneys with suboptimal histology remained functional at 5 years. Our findings suggest that histologic findings on postreperfusion biopsy associate with outcomes after deceased donor but not living donor renal transplants, thus donor death and organ preservation-related factors may be of greater prognostic importance. Discarding donated kidneys on the basis of histologic factors may be inappropriate and merits further study., (Copyright © 2017 by the American Society of Nephrology.)

The use of hypothermic machine perfusion (HMP) has recently been used to show an improvement in both standard and extended criteria donor liver grafts but creating a more dynamic preservation environment that can be supplemented with a variety of additives to aid in cold temperature metabolism and vasodilatation. Increasing the benefits of HMP, we explore the use of α-tocopherol in reducing inflammatory markers and apoptotic pathways to reduce the incidence of preservation injury. We explored the use of a donation after cardiac death (DCD) rodent model to test the additive benefits of α-tocopherol in HMP. The addition of α-tocopherol reduced the level of alanine aminotransferase (ALT) over the course of reperfusion as well, reduced the levels of inflammatory cytokines within a 90 minute reperfusion biopsy. Further benefit was seen with α-tocopherol through the reduction of the level of caspase 3/7 in the circulation, shown to be a result of the reduction of the levels of Cytochrome C mRNA. Liver perfusion with Vasosol® and HMP could benefit further from the addition of α-tocopherol to existing formulations of Vasosol®., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Hepatic inflow clamping during hepatectomy introduces ischemia-reperfusion (I/R) injury, and many authors regard the addition of caval occlusion as adding increased risk. Ischemic preconditioning (IPC) is one of the protective strategies employed to reduce I/R injury in animal experiments and limited clinical series. The aim of the present study was to determine the impact of systematic adoption of IPC in patients undergoing complex hepatectomy under total hepatic vascular exclusion (TVE) based on outcomes review., Methods: The records of 93 patients who underwent major hepatectomy involving TVE at our center from February 1998 to December 2008 were reviewed. These patients were divided into two groups: group 1 (n = 55, TVE alone) and group 2 (n = 38, TVE with IPC). IPC was performed by portal triad clamping for 10 min followed by 3-5 min of reperfusion prior to TVE and resection., Results: The two groups were comparable regarding demographics, underlying liver diseases, indications for hepatectomy, duration of TVE, and preoperative liver and kidney function tests. Overall postoperative laboratory results of liver function tests were not significantly different between the two groups. Creatinine levels and prothrombin times were not significantly different between the groups. The use of IPC had no impact on the duration of the operation, blood loss, or hospital stay. The morbidity rates were 37.5 and 34.2 %, respectively., Conclusions: Our adoption of IPC as a protective strategy against I/R injury under TVE did not affect operative or laboratory parameters and clinical outcomes when compared to continuous clamping for comparable ischemic periods.

Background: Protein C is a natural thrombin antagonist produced by hepatocytes. Its levels are low in liver failure and predispose patients to increased risk for thrombosis. Little is known about the relationship between protein C activity and hepatic function after orthotopic liver transplantation (OLT)., Methods: We measured protein C activity of 41 patients undergoing liver transplantation by the Staclot method (normal range, 70%-130%) preoperatively and then daily on postoperative days (POD) 0-5., Results: The mean protein C activity was low before OLT (34.3 ± 4.3%) and inversely correlated with the preoperative Model for End-Stage Liver Disease score (Spearman's r = -0.643; P < .0001). Mean activity increased significantly on POD 1 (58.9 ± 4.5%), and remained above preoperative levels through POD 5. Ten patients developed metabolic liver dysfunction defined by a serum total bilirubin >5 mg/dL on POD 7. These patients had significantly lower protein C activity from POD 3 (47.2 ± 9.6% vs 75.9 ± 5.8%; P = .01) to POD 5. Preoperative protein C activity correlated inversely with the severity of liver failure as indicated by preoperative MELD score., Conclusion: Protein C activity recovered rapidly in patients with good allograft function but remained significantly lower in patients who had limited metabolic function as evidenced by increased total bilirubin levels., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Our center has recently observed foreign carbohydrate-appearing particles (FP) on transplant postreperfusion biopsy specimens: (PRBx)., Methods: To further characterize FPs, we reviewed all renal transplant RBx (30-45 minutes) performed between September 1, 2004 and December 3, 2005. Donor, preservation, and outcome variables were collected among patients with FP., Results: A total of 135 PRBx were performed (45 deceased donors [DD] and 90 live donors [LD]). Fifteen PRBx demonstrated FP. All 15 cases were DD kidneys that underwent machine perfusion (MP) on the Waters RM3 (Waters Medical Systems, Rochester, Minn, United States) with Belzer MP solution (Trans Med, Elk River, Minn, United States). Donor age was 39.8 +/- 15.7 years. Terminal creatinine level was 1.45 +/- 0.8 mg/dL. Two of 15 were flushed in situ with HTK solution (no starch). Cold ischemia time was 28.8 +/- 9.1 hours with 14.3 +/- 5.1 hours of MP. In 13 of 15 patients, perfusion parameters were excellent (flow > 100 mL; resistance < .35). CHARACTERISTICS OF FP: Particles were 10-30 mu and globular in shape. FP were not visible on hematoxylin and eosin stain, but stained strongly periodic acid-Schiff-(PAS) positive and were refractile under polarized light. FP were seen segmentally within glomerular capillaries in all cases and in peritubular capillaries in 3. In 11 of the 15 cases with FP, focal glomerular fibrin thrombi or intracapillary neutrophil margination was seen. Ten of 15 patients with FP had a biopsy within the first week with no identifiable FP., Outcomes: Recipient age was 45.3 +/- 11.6 years. Eight patients (53.3%) had delayed graft function. Biopsy-proven rejection occurred in 3 patients (20%). Three-month creatinine level was 1.59 +/- 0.35 mg/dL. One graft was lost to early thrombosis in a patient with a hypercoagulable state and 1 patient died of sepsis at 2 months. All remaining 13 patients are alive with excellent graft function at a median follow-up of 6.7 months (range, 3-17 months)., Conclusions: Microscopic intrarenal particles may be seen on DD kidney PRBx after MP. These FPs likely originate from surgical gloves. FPs are too small to be captured by standard filters but clear spontaneously and do not have deleterious effects on renal function or outcomes.