Liver Graft Research Articles

Comparison of clinical outcomes using the left and right liver grafts in adult-to-adult living donor liver transplantation: a retrospective cohort study using the Korean Organ Transplantation Registry

Comparison of clinical outcomes using the left and right liver grafts in adult-to-adult living donor liver transplantation: a retrospective cohort study using the Korean Organ Transplantation Registry

Left at right heterotopic implantation of left liver graft in adult-to-adult living donor liver transplantation: the technical concern for decision-making

Left at right heterotopic implantation of left liver graft in adult-to-adult living donor liver transplantation: the technical concern for decision-making

Quantifying the Disadvantage of Small Recipient Size on the Liver Transplantation Waitlist, a Longitudinal Analysis Within the Eurotransplant Region.

Small adult patients with end-stage liver disease waitlisted for liver transplantation may face a shortage of size-matched liver grafts. This may result in longer waiting times, increased waitlist removal, and waitlist mortality. This study aims to assess access to transplantation in transplant candidates with below-average bodyweight throughout the Eurotransplant region. Patients above 16 y of age listed for liver transplantation between 2010 and 2015 within the Eurotransplant region were eligible for inclusion. The effect of bodyweight on chances of receiving a liver graft was studied in a Cox model corrected for lab-Model for End-stage Liver Disease (MELD) score updates fitted as time-dependent variable, blood type, listing for malignant disease, and age. A natural spline with 3 degrees of freedom was used for bodyweight and lab-MELD score to correct for nonlinear effects. At the end of follow-up, the percentage of transplanted, delisted, and deceased waitlisted patients was 49.1%, 17.9%, and 24.3% for patients with a bodyweight <60 kg (n = 1267) versus 60.1%, 15.1%, and 18.6% for patients with a bodyweight ≥60 kg (n = 10 520). To reach comparable chances for transplantation, 60-kg and 50-kg transplant candidates are estimated to need, respectively, up to 2.8 and 4.0 more lab-MELD points than 80-kg transplant candidates. Decreasing bodyweight was significantly associated with decreased chances to receive a liver graft. This resulted in substantially longer waiting times, higher delisting rates, and higher waitlist mortality for patients with a bodyweight <60 kg.

The effect of donor graft type on survival after liver transplantation for hepatoblastoma in children.

Liver transplantation (LT) is the only potentially curative option for children with unresectable hepatoblastoma (HBL). Although post-transplant outcomes have improved in the contemporary era, the impact of donor graft type on survival remains unclear. Using the United Network for Organ Sharing database (02/2002-06/2021), demographics, clinical characteristics, and patient and graft survival were analyzed in children (<18 years) who underwent LT for HBL according to donor graft type. The Kaplan-Meier method, log-rank tests, and Cox regression modeling were used to evaluate the effect of whole, partial, and split deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) on patient and graft survival. A total of 590 pediatric HBL LT recipients (344 whole graft DDLT; 62 partial graft DDLT; 139 split graft DDLT; 45 LDLT) were included. During 2012-2021 the proportion of LDLTs for HBL decreased to about 5% compared with about 11% during 2002-2011. No significant differences were identified by donor graft type in either patient survival (log-rank test, p = .45) or graft survival (log-rank test, p = .69). The results remained similar during the 2002-2011 era, while during the 2012-2021 era, split graft DDLT was associated with decreased graft loss risk versus whole graft DDLT (hazard ratio: 0.48, 95% confidence interval: 0.23-0.99, p = .046) without any other significant between-group differences. Utilizing non-whole liver grafts can increase access to LT in children with unresectable HBL while ensuring favorable outcomes. LDLT is underutilized in children with HBL in the United States, and efforts to explore LDLT options should be undertaken.

A propensity score matched analysis of liver transplantation outcomes in the setting of preservation solution shortage

The recent shortage of the University of Wisconsin (UW) solution prompted increased utilization of histidine-tryptophan-ketoglutarate (HTK) solution for liver graft preservation. This contemporary study analyzed deceased donor liver transplant outcomes following preservation with HTK vs UW. Patients receiving deceased donor liver transplantations between January 1, 2019, and June 30, 2022, were retrospectively identified utilizing the Organ Procurement and Transplant Network database, stratified by preservation with HTK vs UW, and a propensity score matching analysis was performed. Outcomes assessed included rates of primary nonfunction, graft survival, and patient survival. There were 4447 patients in each cohort. Primary nonfunction occurred in 60 (1.35%) patients in the HTK group vs 25 (0.54%) in the UW group (P < .001). HTK was associated with lower 90-day graft survival (94.39% vs 96.09%; P < .001) and 90-day patient survival (95.97% vs 97.38%; P = .001). Unmatched donation after cardiac death-specific analysis of HTK vs UW demonstrated respective rates of primary nonfunction of 1.63% vs 0.82% (P = .20), 90-day graft survival of 92.50% vs 95.29% (P = .069), and 90-day patient survival of 93.90% vs 96.35% (P = .077). These results suggest that HTK may not be an equivalent preservation solution for deceased donor liver transplantation.

Efficacy, Safety, and Health-Related Quality of Life (HRQOL) in Patients with Sickle Cell Disease (SCD) Who Have Received Lovotibeglogene Autotemcel (Lovo-cel) Gene Therapy: Up to 60 Months of Follow-up

Introduction: Lovo-cel gene therapy uses autologous transplantation of hematopoietic stem and progenitor cells (HSPC) transduced with the BB305 lentiviral vector encoding a modified β-globin gene, which produces an anti-sickling hemoglobin (Hb), HbA T87Q. The phase 1/2 HGB-206 (NCT02140554) and phase 3 HGB-210 (NCT04293185) studies of lovo-cel are the largest clinical trials of gene therapy in SCD to date. We report efficacy and safety from these studies, including the first data from adult and pediatric patients (age 12 to &amp;lt;18 years) in HGB-210, and HRQOL data from HGB-206. Methods: This analysis includes patients from HGB-206 Group C and HGB-210 who received lovo-cel using the current HSPC mobilization and manufacturing process. Patients with SCD and recurrent severe vaso-occlusive events (VOEs) or history of overt stroke underwent plerixafor mobilization and apheresis followed by myeloablative busulfan conditioning and lovo-cel infusion. After 24 months of follow-up post lovo-cel infusion, patients enrolled in the long-term study LTF-307 (NCT04628585). Lab evaluations, SCD-related outcomes (eg, resolution of VOEs), globin response (a composite endpoint evaluating HbA T87Q percentage and total Hb), and safety are reported up to 60 months. An independent Event Adjudication Committee confirmed VOEs met protocol criteria. HRQOL data from Patient-Reported Outcomes Measurement Information System (PROMIS)-57 domains of pain interference, fatigue, and pain intensity are reported up to 48 months. Results:This analysis includes47 patients (HGB-206 Group C, n=36; HGB-210, n=11; male, 59.6%; median [range] age, 23 y [12-38]) who received a lovo-cel infusion as of Feb 13, 2023. Median (range) follow-up was 35.5 months (0.3-61.0). Median (range) time to neutrophil and platelet engraftment was 20 days (12-35) and 35 days (19-136). Peripheral blood vector copy number remained stable (median &amp;gt;1 c/dg through follow-up). Median HbA T87Q levels were ≥4.5 g/dL from 6 months post infusion to last study visit. Median (range) total Hb level increased from 8.7 g/dL (6.1-12.5) at relative baseline to 11.8 g/dL (8.4-15.0) at last visit; median percent HbA T87Q of nontransfused total Hb was ≈40% or more ( Figure). Of 33 evaluable patients (ie, ≥18 months follow-up and ≥4 VOEs in the 2 years before enrollment), 30 (90.9%) and 32 (97.0%) had complete resolution of VOEs and severe VOEs during the 6-18 months post infusion, vs a median (range) of 3.5 (1.5-16.5) and 3.0 (0.5-13.0) events/year in the 2 years before enrollment. Additional efficacy analyses in subgroups (eg, stroke history, α-globin genotype) will be presented. Among patients who had globin response or who had ≥18 months follow-up (n=38), 33 (86.8%) achieved globin response. Hemolysis markers (eg, reticulocytes, total bilirubin, lactate dehydrogenase) approached normal levels. Among all 47 patients, 44 (93.6%) had ≥1 AE of grade ≥3 after lovo-cel infusion; the most common of which were stomatitis (33 [70.2%] patients) and thrombocytopenia (28 [59.6%]). Serious AEs were reported for 26 (55.3%) patients, the most common of which was chronic pain/acute exacerbation of chronic pain (3 [6.4%]; 2 chronic neuropathic pain and 1 chronic pain associated with anxiety). One patient with -α3.7/-α3.7 genotype was diagnosed with myelodysplastic syndrome with stable complete blood counts 30 months post infusion; updated data to be presented. No veno-occlusive liver disease, graft failure, replication-competent lentivirus, or vector-mediated insertional oncogenesis was observed. Lovo-cel treatment regimen largely reflected known side effects of HSPC collection and busulfan conditioning regimen. A total of 25 patients (all from HGB-206 Group C; age ≥18 y) had evaluable HRQOL data. Mean scores for PROMIS-57 domains of pain intensity, pain interference, and fatigue improved (ie, decreased) over time up to 48 months ( Table). Conclusion: One-time treatment with lovo-cel resulted in sustained HbA T87Q production and near-complete resolution of VOEs and severe VOEs up to 18 months post treatment; the safety profile was consistent with underlying SCD and myeloablative conditioning. Patients reported sustained improvements in pain intensity, pain interference, and fatigue. Ongoing long-term follow-up will continue to provide important information on efficacy, safety, and patient experience post lovo-cel treatment.

Outcomes of liver transplantation with thoracoabdominal normothermic regional perfusion: a matched-controlled initial experience in Spain.

Thoracoabdominal (TA) normothermic regional perfusion (NRP) should allow the safe recovery of heart and liver grafts simultaneously in the context of controlled donation after circulatory death (cDCD). We present the initial results of cDCD liver transplantation with simultaneous liver and heart procurement in Spain until October 2021. Outcomes were compared with a matched cohort of cDCD with abdominal NRP (A-NRP) from participating institutions. Primary endpoints comprised early allograft dysfunction (EAD) or primary non-function (PNF), and the development of ischemic-type biliary lesions (ITBL). Six transplants were performed using cDCD with TA-NRP during the study period. Donors were significantly younger in the TA-NRP group than in the A-NRP group (median 45.6 years and 62.9 years respectively, p = 0.011), with a median functional warm ischemia time of 12.5 min in the study group and 13 min in the control group. Patient characteristics, procurement times, and surgical baseline characteristics did not differ significantly between groups. No patient in the study group developed EAD or PNF, and over a median follow-up of 9.8 months, none developed ITBL or graft loss. Extending A-NRP to TA-NRP for cardiac procurement may be technically challenging, but it is both feasible and safe, showing comparable postoperative outcomes to A-NRP.

Screening for mitochondrial function before use-routine liver assessment during hypothermic oxygenated perfusion impacts liver utilization

To report on a concept of liver assessment during ex situ hypothermic oxygenated perfusion (HOPE) and its significant impact on liver utilization. An analysis of prospectively collected data on donation after circulatory death (DCD) livers, treated by HOPE at our institution, during a 11-year period between January 2012 and December2022. Four hundred and fifteen DCD Maastricht III livers were offered during the study period in Switzerland, resulting in 249 liver transplants. Of those, we performed 158 DCD III liver transplants at our institution, with 1-year patient survival and death censored graft survival (death with functioning graft) of 87 and 89%, respectively, thus comparable to benchmark graft survivals of ideal DBD and DCD liver transplants (89% and 86%). Correspondingly, graft loss for primary non-function or cholangiopathy was overall low, i.e., 7/158 (4.4%) and 11/158 (6.9%), despite more than 82% of DCD liver grafts ranked high (6-10 points) or futile risk (>10 points) according to the UK-DCD score. Consistently, death censored graft survival was not different between low-, high-risk or futile DCD III livers. The key behind these achievements was the careful development and implementation of a routine perfusate assessment of mitochondrial biomarkers for injury and function, i.e., release of flavin mononucleotide from complex I, perfusate NADH, and mitochondrial CO2 production during HOPE, allowing a more objective interpretation of liver quality on a subcellular level, compared to donor derived data. HOPE after cold storage is a highly suitable and easy to perform perfusion approach, which allows reliable liver graft assessment, enabling surgeons to make a fact based decision on whether or not to implant the organ. HOPE-treatment should be combined with viability assessment particularly when used for high-risk organs, including DCD livers or organs with relevant steatosis. This study was supported by the Swiss National Foundation (SNF) grant 320030_189055/1 to PD.

Interleukin-6 Levels During Normothermic Machine Perfusion Impact Postreperfusion Hemodynamics of Liver Graft Recipients: A Prospective Single-center Observational Study.

Hemodynamic instability after liver graft reperfusion increases recipient morbidity after liver transplantation. The etiologies of hemodynamic disturbances appear to be multifactorial and are poorly understood. Normothermic machine perfusion (NMP) provides an opportunity to analyze graft quality prior to transplantation. In the present study, we aim to investigate the influence of interleukin-6 (IL-6) levels during NMP on postreperfusion hemodynamics of the recipient. Consecutive NMP-liver transplants at a single-center were prospectively analyzed. Perfusate samples were collected at the beginning, after 6 h, and at the end of perfusion and analyzed for IL-6 levels. Mean arterial pressure (MAP) and catecholamine consumption during surgery were recorded. IL-6 levels at the end of NMP were correlated to donor and perfusion characteristics as well as changes in MAP and catecholamine requirements during the anhepatic and reperfusion phase. IL-6 perfusate measurements were assessed in 77 livers undergoing NMP and transplantation. Donor age, sex, cold ischemic time, and NMP time did not correlate with IL-6 levels. Perfusates of donation after circulatory death grafts showed higher IL-6 levels at the end of NMP than donation after brain death grafts. However, IL-6 levels at the end of NMP correlated with catecholamine requirements and MAP in the reperfusion phase. Per log10 increase in IL-6 levels, an increase of 42% points in administered catecholamine dose was observed, despite MAP being decreased by 3.6% points compared to baseline values. IL-6 levels may be a predictor for recipient hemodynamic instability during liver reperfusion. Larger studies are needed to confirm this finding.

Histological Assessment of the Bile Duct before Liver Transplantation: Does the Bile Duct Injury Score Predict Biliary Strictures?

Histological injury to the biliary tree during organ preservation leads to biliary strictures after liver transplantation. The Bile Duct Injury (BDI) score was developed to assess histological injury and identify the grafts most likely to develop biliary strictures. The BDI score evaluates the bile duct mural stroma, peribiliary vascular plexus (PVP) and deep peribiliary glands (DPGs), which were correlated with post-transplant biliary strictures. However, the BDI score has not been externally validated. The aim of this study was to verify whether the BDI score could predict biliary strictures at our transplant centre. Brain-dead donor liver grafts transplanted at a single institution from March 2015 to June 2016 were included in this analysis. Bile duct biopsies were collected immediately before transplantation and assessed for bile duct injury by two blinded pathologists. The primary outcome was the development of clinically significant biliary strictures within 24 months post-transplant. Fifty-seven grafts were included in the study which included 16 biliary strictures (28%). Using the BDI score, mural stromal, PVP and DPG injury did not correlate with biliary strictures including Non-Anastomotic Strictures. Severe inflammation (>50 leucocytes per HPF) was the only histological feature inversely correlated with the primary outcome (absent in the biliary stricture group vs. 41% in the no-stricture group, p = 0.001). The current study highlights limitations of the histological assessment of bile duct injury. Although all grafts had bile duct injury, only inflammation was associated with biliary strictures. The BDI score was unable to predict post-transplant biliary strictures in our patient population.

Prospective Study to Analyze the Concordance Between a Standardized Visual Method With Pathology to stratify Nonalcoholic Fatty Liver Disease in Cadaveric Liver Grafts Evaluated for Transplantation.

The main challenge of liver transplantation is the discrepancy in demand and availability. Marginal grafts or full organs from donors with expansion criteria have been considered to reduce the shortage and assist a greater number of patients. Nonalcoholic fatty liver disease (NAFLD) is one of the most important defining criteria for expanded criteria organs. The present study proposes that an organized visual analysis method could correctly identify and classify NAFLD and organ viability without the need for liver biopsy and its logistical concerns. Pictures from the grafts were taken at a standardized method (same distance, light conditions, and register device) before and after the perfusion. The visual liver score (VLS) was applied by transplant surgeons; biopsies of the grafts were analyzed by a pathologist in a double-blind design. Score performance and interobserver agreement for NAFLD detection and grading, as graft viability evaluation, were calculated. Fifty-seven grafts were analyzed. At least 1 previous expansion criterion was presented by 59.64% of donors. The prevalence of NAFLD was 94.73%, with 31.57% borderline nonalcoholic steatohepatitis and 5.26% nonalcoholic steatohepatitis. Steatosis was identified with 48.68% (preperfusion) and 64.03% (postperfusion) accuracy. NAFLD stratification was performed with 49.53% (preperfusion) and 46.29% (postperfusion) accuracy. Viability related to NAFLD was identified with 51.96% (preperfusion) and 48.52% (postperfusion) accuracy. Interobserver agreement was moderate for total VLS and poor for individual components of VLS. Although a standardized method was not reliable enough for visual evaluation of NALFD compared with pathology, efforts should be made to expand access to biopsy. Further studies are needed to understand whether the VLS needs to be adapted or even excluded in the liver transplant scenario, to assess the importance of ectoscopy related to posttransplant clinical outcomes, and to determine its role in graft selection.

Unusual grafts for living-donor liver transplantation

PurposeUnusual grafts, including extended left liver plus caudate lobe, right anterior section, and right posterior section grafts, are alternatives to left and right lobe grafts for living-donor liver transplantation. This study aimed to investigate unusual grafts from the perspectives of recipients and donors.MethodsFrom 2016 to 2021, 497 patients received living-donor liver transplantation at Severance Hospital. Among them, 10 patients received unusual grafts. Three patients received extended left liver plus caudate lobe grafts, two patients received right anterior section grafts, and five patients received right posterior section grafts. Liver volumetrics and anatomy were analyzed for all recipients and donors. We collected data on laboratory examinations (alanine aminotransferase, total bilirubin, international normalized ratio), imaging studies, graft survival, and complications. A 1:2 ratio propensity-score matching method was used to reduce selection bias and balance variables between the unusual and conventional graft groups.ResultsThe median of Model for End-stage Liver Disease score of unusual graft recipients was 13.5 (interquartile range 11.5–19.3) and that of graft–recipient weight ratio was 0.767 (0.7–0.9). ABO incompatibility was observed in four cases. The alanine aminotransferase level, total bilirubin level, and international normalized ratio decreased in both recipients and donors. Unusual and conventional grafts had similar survival rates (p = 0.492). The right and left subgroups did not differ from each counter-conventional subgroup (p = 0.339 and p = 0.695, respectively). The incidence of major complications was not significantly different between unusual and conventional graft recipients (p = 0.513). Wound seromas were reported by unusual graft donors; the complication ratio was similar to that in conventional graft donors (p = 0.169).ConclusionAlthough unusual grafts require a complex indication, they may show feasible surgical outcomes for recipients with an acceptable donor complication.

Using extracorporeal membrane oxygenation in donations after cardiac death or brain death: A single-center experience and long-term outcome.

The use of extended criteria donors is a routine practice that sometimes involves extracorporeal membrane oxygenation (ECMO) in donations after cardiac death or brain death. We performed a retrospective study in a single center from January 2006 to December 2019. The study included 90 deceased donor liver transplants. The patients were divided into three groups: the donation after brain death (DBD) group (n = 58, 64.4%), the DBD with ECMO group (n = 11, 12.2%) and the donation after cardiac death (DCD) with ECMO group (n = 21, 23.3%). There were no significant differences between the DBD with ECMO group and the DBD group. When comparing the DCD with ECMO group and the DBD group, there were statistically significant differences for total warm ischemia time (p < 0.001), total cold ischemia time (p = 0.023), and split liver transplantation (p < 0.001), and there was significantly poor recovery in regard to total bilirubin level (p = 0.027) for the DCD with ECMO group by repeated measures ANOVA. The 5-year survival rates of the DBD, DBD with ECMO, and DCD with ECMO groups were 78.1%, 90.9%, and 75.6%, respectively. The survival rate was not significantly different when comparing the DBD group to either the DBD with ECMO group (p = 0.435) or the DCD with ECMO group (p = 0.310). Using ECMO in donations after cardiac death or brain death is a good technology, and it contributed to 35.6% of the liver graft pool.

The Effect of New Acuity Circle Policy on Simultaneous Liver and Kidney Transplantation in the United States

New deceased donor liver allocation policy using an acuity circle (AC)-based model was implemented on February 4th, 2020. The effect of AC policy on simultaneous liver-kidney transplantation (SLKT) remains unknown. The aim of this study was to assess the effect of AC policy on SLKT waitlist mortality, transplant probability, and post-transplant outcomes. Using the United Network for Organ Sharing database, 4908 adult SLKT candidates during two study periods, pre-AC (Aug-2017 to Feb-2020, N=2770) and post-AC (Feb-2020 to Dec-2021, N=2138) were analyzed. Outcomes included 90-day waitlist mortality, transplant probability, and post-transplant patient and graft survival. Compared to pre-AC period, SLKT recipients during post-AC period had higher median model for end-stage liver disease (MELD) score (24 vs 23, P<0.001), and less percentage of MELD exception (4.6% vs 7.7%, P=0.001). The 90-day waitlist mortality was same, but the probability of SLKT increased in post-AC period (P<0.001). Post-AC period also saw increased utilization of donation after cardiac death organs (11% vs 6.4%, P<0.001) and decreased rates of transplantation among Black candidates (7.9% vs 13%). After risk adjustment, post-AC period was not associated with any significant difference in 90-day waitlist mortality (sub-distribution hazard ratio [sHR] 0.80; 95% CI 0.56-1.16, P=0.24), and a higher 90-day probability of SLKT (sHR 1.68; 95% CI 1.41-1.99, P<0.001). During post-transplant period, one-year patient survival, liver and kidney graft survival were comparable between two study periods. The AC liver allocation policy was associated with increased transplant probability of adult SLKT candidates without decreasing waitlist mortality, post-transplant patient survival, or liver and kidney graft survival.

Role of perfusion medium in rewarming machine perfusion from hypo- to normothermia.

Gradual warming up of cold stored organ grafts using a controlled machine perfusion protocol facilitates restitution of cellular homeostasis and mitigates rewarming injury by adapted increase of temperature and metabolism. The aim of the present study was to compare intra- and extracellular type perfusion media for the use in machine perfusion-assisted rewarming from hypo- to normothermia. Rat livers were retrieved 20 min after cardiac arrest. After 18 h of cold storage (CS) with or without additional 2 h of rewarming machine perfusion from 8°C up to 35°C with either diluted Steen solution or with Belzer MPS, liver functional parameters were evaluated by an established exvivo reperfusion system. Rewarming machine perfusion with either solution significantly improved graft performance upon reperfusion in terms of increased bile production, less enzyme release, and reduced lipid peroxidation compared to CS alone. Cellular apoptosis (release of caspase-cleaved keratin 18) and release of tumor necrosis factor were only reduced significantly after machine perfusion with Belzer MPS. Histological evaluation did not disclose any major morphological damage in any of the groups. Within the limitation of our model, the use of Belzer MPS seems to be an at least adequate alternative to a normothermic medium like Steen solution for rewarming machine perfusion of cold liver grafts.

Combined Haploidentical Hematopoetic Stem Cell Transplantation and Liver Transplantation in a Pediatric Patient

Solid organ transplantation from the same donor is an established procedure for end-stage organ failure that developed after a previous hematopoietic stem cell transplantation (HSCT); however, it is rarely done in patients transplanted with unmanipulated haplo-HSCT. There are no pediatric reports regarding the long-term performance of organ transplantation after haplo-HSCT with post-transplant cyclophosphamide (PTCY).&#x0D; A juvenile myelomonocytic leukemia patient, who underwent unmanipulated haplo-HSCT with PTCY from her mother at the age of 3 years, developed chronic liver graft versus host disease (GvHD) which was refractory to specific GvHD treatment. Liver transplantation (LT) from her mother (the donor of her haplo-HSCT) was decided as the next line of treatment.&#x0D; LT was performed on day 540 post-HSCT, and the donor's left lateral segment was appropriately removed and attached to the recipient. The symptoms of GvHD completely regressed in a month. The patient died on day 121 after LT, because of a possible hepato-pulmonary syndrome.&#x0D; Organ failure can develop after allo-HSCT secondary to GvHD and therefore performing HSCT from a haplo-donor may be superior to a matched unrelated donor in terms of subsequent organ transplantation for organ failure.

Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure.

Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs). Decellularized scaffolds seeded entirely with human cells were shown to adhere to stringent sterility and safety guidelines and demonstrated increased functionality when compared to grafts seeded with primary porcine liver cells (PPLCs). BELs with PHLCs were able to clear more ammonia than PPLCs and demonstrated lower perfusion pressures during patency testing. Additionally, to determine the full therapeutic potential of BELs seeded with PHLCs, longer culture periods were assessed to address the logistical constraints associated with manufacturing and transporting a product to a patient. The fully humanized BELs were able to retain their function after cold storage simulating a product transport period. Therefore, this study demonstrates the manufacture of bioengineered liver grafts and their potential in the clinical setting as a treatment for ALF.

The effects of acuity circle policy on racial disparity in liver transplantation

BackgroundA new deceased donor liver allocation policy using an acuity circle–based model was implemented with the goal of providing equitable access to liver transplantation. We assessed the effect of the acuity circle policy on racial disparities in liver transplantation by analyzing waitlist mortality, transplant probability, and post-transplant outcomes. MethodsWe conducted a retrospective analysis of 23,717 adult liver transplantation candidates listed during the pre-acuity circle period and 21,051 during the post–acuity circle period (N = 44,768) in the United Network for Organ Sharing database from February 2020 to December 2021. ResultsAcuity circle–policy implementation was not associated with any significant difference in 90-day waitlist mortality but increased the 90-day probability of all candidates. Implementation did not decrease 90-day waitlist mortality but increased the 90-day transplant probability for all patients. One-year patient and liver graft survival were comparable between the study periods for all recipients, but Black recipients had higher rates of 1-year post–liver transplantation mortality and liver graft failure in both periods. ConclusionAlthough the implementation of the acuity circle policy is associated with an increase in transplant probability in White, Black, and Hispanic liver transplantation candidates, it did not change their waitlist mortality, nor did it lead to any improvement in the preexistent worse post-transplant outcomes in Black liver transplantation recipients.

The short and long-term prognostic influences of liver grafts with high bilirubin levels at the time of organ recovery.

Donors with hyperbilirubinemia are often not utilized for liver transplantation (LT) due to concerns about potential liver dysfunction and graft survival. The potential to mitigate organ shortages using such donors remains unclear. This study analyzed adult deceased donor data from the United Network for Organ Sharing database (2002-2022). Hyperbilirubinemia was categorized as high total bilirubin (3.0-5.0mg/dL) and very high bilirubin (≥5.0mg/dL) in brain-dead donors. We assessed the impact of donor hyperbilirubinemia on 3-month and 3-year graft survival, comparing these outcomes to donors after circulatory death (DCD). Of 138622 donors, 3452 (2.5%) had high bilirubin and 1999 (1.4%) had very high bilirubin levels. Utilization rates for normal, high, and very high bilirubin groups were 73.5%, 56.4%, and 29.2%, respectively. No significant differences were found in 3-month and 3-year graft survival between groups. Donors with high bilirubin had superior 3-year graft survival compared to DCD (hazard ratio .83, p=.02). Factors associated with inferior short-term graft survival included recipient medical condition in intensive care unit (ICU) and longer cold ischemic time; factors associated with inferior long-term graft survival included older donor age, recipient medical condition in ICU, older recipient age, and longer cold ischemic time. Donors with ≥10% macrosteatosis in the very high bilirubin group were also associated with worse 3-year graft survival (p=.04). The study suggests that despite many grafts with hyperbilirubinemia being non-utilized, acceptable post-LT outcomes can be achieved using donors with hyperbilirubinemia. Careful selection may increase utilization and expand the donor pool without negatively affecting graft outcome.

Liver retransplantation in the modern concept of treatment of its terminal pathology (literature review)

The work is devoted to the analysis of modern literature data and approaches in performing repeated liver transplantation. The most frequent causes of liver graft loss are PNFT, HAT, recurrent initial disease and chronic rejection. The leading indication for retransplantation in children is HAT. The one-year survival rate after retransplantation is approximately 75%. Reducing the cost of organ retransplantation and the cost-effectiveness of the procedure are controversial issues. Mathematical modeling has identified several significant recipient and donor factors affecting the outcomes of retransplantation. Despite ethical and economic considerations, retransplantation is the only option for transplant patients whose grafts have failed to engraft. The decision to retransplant should be made with some caution, with full multi-type approach in large multidisciplinary transplant centers.