Mao, Shennen

ABSTRACT Background With increasing use of donation after circulatory death (DCD) donor grafts, the need for accurate risk‐stratification tools in liver transplantation has become critical. Machine perfusion has been shown to improve both graft and patient survival. However, existing prediction models were developed in the static cold storage (SCS) era and their accuracy when using machine perfusion remains unknown. Our study aims to study if current scoring systems can predict graft and patient survival for DCD livers preserved using normothermic machine perfusion (NMP). Methods This was a retrospective study of patient and graft survival in a two‐center U.S. DCD NMP cohort ( n = 532) between January 2022 and December 2024. Predicted graft and patient survival rates were obtained from established risk scoring systems, including the United Kingdom DCD risk score (UK‐DCD), Early Allograft Dysfunction (EAD) Olthoff score, Liver Graft Assessment Following Transplantation (L‐GrAFT 7 ) score, Donor Risk Index (DRI), Balance of Risk (BAR) score, and Survival Outcomes Following Liver Transplant (SOFT) score. Model discrimination was assessed using receiver operating characteristic (ROC) curves (C‐statistics). Survival outcomes across risk strata were estimated and compared using Kaplan‐Meier (KM) analysis. Results Across scoring systems, predicted survival consistently underestimated actual graft and patient survival in the NMP DCD cohort. The DRI, SOFT, EAD and L‐GrAFT 7 did not demonstrate predictive value. UK‐DCD predicted ≤85% and <40% 1‐year graft survival for its high‐risk and “futile” groups, whereas observed rates were 93.7% and 86.8%. BAR low‐risk predicted >60% 5‐year survival but 94.2% was observed; the high‐risk group predicted <60% and observed was 53.3%. Despite underestimations and generally poor C‐statistics, in KM stratification, high‐risk groups still showed statistical differences in the UK‐DCD categories ( p = 0.007), and in SOFT score groups ( p < 0.001). No statistical difference was seen in BAR ( p = 0.36), DRI ( p = 0.36), EAD ( p = 0.12), or L‐GrAFT 7 ( p = 0.75). Conclusion Existing liver transplant risk scores show limited predictive value for donor‐related risk factors in the NMP era, whereas recipient‐related factors remain somewhat predictive, despite overestimating risk. Early allograft dysfunction metrics were not reliable predictors of short or long‐term outcomes. Future risk models should integrate machine‐perfusion parameters and refined donor variables to reflect outcomes more accurately in contemporary DCD liver transplantation.

Importance Ischemia-reperfusion injury contributes to graft dysfunction after liver transplant. Hypothermic oxygenated perfusion (HOPE) has been shown to improve liver function, but its benefit in extended criteria donors in a US population remains unclear. Objective To assess whether back-to-base portal-venous HOPE impacts outcomes after liver transplant in the US. Design, Setting, and Participants The Bridge to HOPE Trial is a multicenter, randomized, open-label trial with 1-year follow-up. The study took place at 15 US liver transplant centers and patients were enrolled between January 2021 and May 2023. Central assessment of complications and cholangiograms for nonanastomotic biliary strictures (NAS) was blinded to treatment arm. Participants included 219 recipients of extended-criteria donor livers after brain death (DBD) and after circulatory death (DCD) who were randomized 1:1 to HOPE after static cold storage (SCS) (n = 109) or SCS only (n = 110). Randomization was performed after liver inspection and acceptance for transplant. Data were analyzed from December 2024 to July 2025. Intervention After SCS and transport, livers underwent portal-venous HOPE until implant, using the VitaSmart HOPE System. Main Outcomes and Measures The primary efficacy end point was early allograft dysfunction (EAD). Other main outcomes included model for early allograft function (MEAF) score, hospital length of stay (LOS), patient and graft survival, and biliary complications. Additional post hoc analyses were performed. Results Overall, 219 patients (82 female [37.4%] and 137 male[62.6%]) were included (DCD, 57 of 219 [26%]) with 97% (212 of 219) completing 12-month follow-up. EAD incidence was 20.2% (22 of 109) with HOPE vs 37.3% (41 of 110) with SCS (rate difference, −17.1%; 95% CI, −27.2 to −7.0; noninferiority P &amp;lt; .001; superiority P = .005). HOPE treatment led to significantly lower MEAF mean (SD) scores (HOPE group, 4.28 [1.75]; control group, 4.82 [1.85]; mean difference, −0.54; 95% CI, −1.02 to −0.06; P = .03) and shorter median LOS (hazard ratio, 1.32; 95% CI, 1.01-1.73; P = .04). NAS on imaging and 1-year survivals were comparable between groups (patients: HOPE group, 106 of 109 [97.2%] vs SCS, 106 of 110 [96.4%]; graft: HOPE group, 104 of 109 [95.4%] vs SCS, 102 of 110 [92.7%]). Post hoc analyses showed numerically less graft loss due to NAS after HOPE (4 vs 1) and less major complications (Clavien-Dindo classification ≥IIIa) per patient, respectively. Conclusions and Relevance Back-to-base portal-venous HOPE was compared with SCS alone for extended risk DBD and DCD livers. The HOPE approach was safe and associated with reduced EAD, MEAF score, and LOS. These findings support the use of HOPE as a pragmatic strategy to improve early posttransplant outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT05045794 .

ABSTRACT Background Ureteral stents are commonly placed during kidney transplantation (KT) to mitigate urologic complications. The objective of this study was to compare clinical outcomes in KT recipients with either early stent removal when attached to the Foley catheter or late removal via cystoscopy when unattached. Methods We conducted a multi‐center retrospective analysis of consecutive living donor KT patients (8/18/21‐4/21/23) stratified into Foley‐attached and unattached stent groups. Outcomes assessed were ureteral stricture, urine leaks, UTIs at 90 days and allograft failure and BKV DNAemia (BK virus DNAemia) at 1 year. Data are reported as mean and standard deviation. Results Among 247 patients with attached and 260 with unattached stents, baseline demographics (age, sex, diabetes) were similar between groups. There was a difference in race (87.9% vs. 77.8% Caucasian; p = 0.004). Foley catheters remained longer in the attached group (3.7 ± 1.8 vs. 3.0 ± 2.0 days; p < 0.001), but stents were removed earlier (3.7 ± 1.8 vs. 21.9 ± 4.7 days; p < 0.001). Comparing attached versus unattached, there were no differences in ureteral stricture (0.4% vs. 1.5%; p = 0.197), urine leak (0.8% vs. 0.4%; p = 0.533), BKV DNAemia (17.7% vs. 16.9%; p = 0.616), or allograft failure (0% vs. 0.8%; p = 0.167). However, UTI incidence by 90 days was lower in the attached group (5.7% vs. 11.9% p = 0.013). Induction therapy differed significantly between groups, with Alemtuzumab more common in the unattached group (58.1% vs. 19.4%, p < 0.001), Basiliximab more common in the attached group (43.3% vs. 35.0%, p < 0.001), and Thymoglobulin more common in the attached group (36.0% vs. 6.9%, p < 0.001). Baseline steroid use was higher in the unattached group (81.9% vs. 57.9%, p < 0.001). Conclusion Early stent removal via connection to the Foley catheter had similarly low rates of ureteral complications while reducing urinary tract infections and avoiding cystoscopic removal.

The 2024 Annual Congress of the International Liver Transplantation Society (ILTS) was from May 1–4 in Houston, Texas, USA, under the theme “Liver Disease and Transplantation: Breaking Barriers and Exploring New Frontiers.” In addition to a robust scientific program, the congress also hosted a hands-on cadaveric robotic liver surgery course, a machine perfusion workshop, and a transesophageal echocardiography course. In this report, the ILTS Vanguard and Basic Sciences Committees present a summary of the congress proceedings.

BACKGROUND: Although most transplant centers preferentially offer minimally invasive approaches to donor nephrectomies, there remains less standardization specific to the kidney extraction site. This study aimed to evaluate incisional hernia occurrence in living kidney donors based on kidney extraction site location. STUDY DESIGN: This was a retrospective study of all donors who underwent minimally invasive living donor nephrectomies at the Mayo Clinic Arizona between 2011 and 2023 with a 2-year external validation cohort from Mayo Clinic Florida and Mayo Clinic Minnesota. The cohort was divided into 2 groups based on the kidney extraction site type: midline infraumbilical and Pfannenstiel. RESULTS: In the primary cohort, incisional hernia occurrence was observed in 1.2% of donors with an infraumbilical midline kidney extraction site compared with 0.1% with a Pfannenstiel extraction site (p = 0.04). Donors with an infraumbilical midline kidney extraction site were more likely to be men (50.8% vs 23.3%, p < 0.0001), have a higher BMI (mean 27.2 vs 26 kg/m2, p < 0.0001), and have current or former tobacco use (p = 0.002). There were no differences in incisional hernia occurrence when comparing minimally invasive surgical techniques (p = 0.52). In the external validation cohort, hernia occurrence was observed in 4.5% of donors with a midline incision compared with 0.0% with a Pfannenstiel incision (p = 0.09). Using combined data from the 3 sites, the use of a Pfannenstiel incision as the extraction site was associated with significantly lower odds of developing a hernia compared with the infraumbilical midline incision (odds ratio 0.06, 95% CI 0.008 to 0.456). CONCLUSIONS: Although the risk of hernia in living kidney donors is generally low, the use of a Pfannenstiel incision for kidney extraction appears to offer an additional incremental reduction in risk.

Background. Normothermic regional perfusion (NRP) has emerged as a vital technique in organ procurement, particularly in donation after circulatory death (DCD) cases, offering the potential to optimize organ utilization and improve posttransplant outcomes. Recognizing its significance, the American Society of Transplant Surgeons (ASTS) convened a work group to develop standardized recommendations for abdominal NRP in the United States. Methods. The workgroup, comprising experts in NRP, DCD, and transplantation, formulated recommendations through a collaborative process involving revisions and approvals by relevant committees and the ASTS council. Four key areas were identified for standardization: Preprocedure communication, NRP procedure, Terminology and documentation, and Mentorship/credentialing. Results. The recommendations encompass a range of considerations, including preprocedure communication protocols to facilitate informed decision-making by transplant centers and organ procurement organizations, procedural guidelines for NRP teams, uniform terminology to clarify the NRP process, and standards for mentorship and credentialing of NRP practitioners. Specific recommendations address logistical concerns, procedural nuances, documentation requirements, and the importance of ongoing quality assurance. Conclusions. The standardized recommendations for abdominal NRP presented in this article aim to ensure consistency, safety, and efficacy in the organ procurement process. By establishing clear protocols and guidelines, the ASTS seeks to enhance organ utilization, honor donor wishes, and uphold public trust in the donation process. Implementation of these recommendations can contribute to the advancement of NRP practices and improve outcomes for transplant recipients.

The mammalian liver's regenerative ability has led researchers to engineer animals as incubators for expansion of human hepatocytes. The expansion properties of human hepatocytes in immunodeficient mice are well known. However, little has been reported about larger animals that are more scalable and practical for clinical purposes. Therefore, we engineered immunodeficient swine to support expansion of human hepatocytes and identify barriers to their clinical application. Immunodeficient swine were engineered by knockout of the recombinase-activating gene 2 ( RAG2 ) and fumarylacetoacetate hydrolase (FAH). Immature human hepatocytes (ihHCs) were injected into fetal swine by intrauterine cell transplantation (IUCT) at day 40 of gestation. Human albumin was measured as a marker of engraftment. Cytotoxicity against ihHCs was measured in transplanted piglets and control swine. We initially detected higher levels of human albumin in cord blood of newborn FAH/ RAG2 -deficient (FR) pigs compared with immunocompetent controls (196.26 ng/dL vs. 39.29 ng/dL, p = 0.008), indicating successful engraftment of ihHCs after IUCT and adaptive immunity in the fetus. Although rare hepatocytes staining positive for human albumin were observed, levels of human albumin did not rise after birth, but declined, suggesting rejection of xenografted ihHCs. Cytotoxicity against ihHCs increased after birth by 3.8% (95% CI: [2.1%–5.4%], p < 0.001) and inversely correlated with declining levels of human albumin ( p = 2.1 × 10 −5 , R 2 = 0.17). Circulating numbers of T cells and B cells were negligible in FR pigs. However, circulating natural killer (NK) cells exerted cytotoxicity against ihHCs. NK cell activity was lower in immunodeficient piglets after IUCT than in naive controls (30.4% vs. 40.1%, p = 0.011, 95% CI for difference [2.7%–16.7%]). In conclusion, ihHCs were successfully engrafted in FR swine after IUCT. NK cells were a significant barrier to expansion of hepatocytes. New approaches are needed to overcome this hurdle and allow large-scale expansion of human hepatocytes in immunodeficient swine. Impact statement There is currently a need for robust expansion of human hepatocytes. We describe an immunodeficient swine model into which we engrafted immature human hepatocytes (ihHCs). We identified the mechanism of the eventual graft rejection by the intact NK cell population, which has not been previously shown to have a significant role in xenograft rejection. By both improving engraftment and reducing NK cell-mediated cytotoxicity toward the graft through intrauterine cell transfer, we confirmed the presence of residual adaptive immunity in this model of immunodeficiency and the ability to induce hyposensitization in the NK cell population by taking advantage of the fetal microenvironment.

Background: Steatotic grafts are increasingly being used for liver transplant (LT); however, the impact of graft steatosis on renal function has not been well described. Methods: A total of 511 allografts from Mayo Clinic Arizona and Minnesota were assessed. We evaluated post-LT acute kidney injury (AKI) patterns, perioperative variables and one-year outcomes for patients receiving moderately steatotic allografts (>30% macrovesicular steatosis, n = 40) and compared them to non-steatotic graft recipients. Results: Post-LT AKI occurred in 52.5% of steatotic graft recipients versus 16.7% in non-steatotic recipients (p < 0.001). Ten percent of steatotic graft recipients required new dialysis post-LT (p = 0.003). At five years, there were no differences for AKI vs. no AKI patient survival (HR 0.95, 95% CI 0.08–10.6, p = 0.95) or allograft survival (HR 1.73, 95% CI 0.23–13.23, p = 0.59) for those using steatotic grafts. Lipopeliosis on biopsy was common in those who developed AKI (61.0% vs. 31.6%, p = 0.04), particularly when the Model for End-Stage Liver Disease (MELD) was ≥20 (88.9%; p = 0.04). Lipopeliosis was a predictor of post-LT AKI (OR 6.0, 95% CI 1.1–34.6, p = 0.04). Conclusion: One-year outcomes for moderately steatotic grafts are satisfactory; however, a higher percentage of post-LT AKI and initiation of dialysis can be expected. Presence of lipopeliosis on biopsy appears to be predictive of post-LT AKI.

Previous large registry studies have demonstrated inferior outcomes for simultaneous liver‐kidney transplantation (SLKT) recipients of grafts from donation after circulatory death (DCD) donors compared with those from donation after brain death (DBD) donors in the era from 2000 to 2010. Given the improving national results in liver transplantation alone using grafts from DCD donors, the present study aimed to investigate if results with DCD‐SLKT have improved in the modern era. Patients undergoing SLKT between 2000 and 2018 were obtained from the United Network for Organ Sharing Standard Analysis and Research file and divided into 2 eras based on the date of SLKT: era 1 (2000‐2010) and era 2 (2011‐2018). Improvement in DCD‐SLKT patient, liver graft, and kidney graft survival rates was seen between era 1 and era 2 (P < 0.001). Concurrently, there was a decrease in the proportion of critically ill (P = 0.02) and retransplant (P = 0.006) candidates undergoing DCD‐SLKT. When DCD‐SLKT in era 2 was compared with a propensity‐matched cohort of DBD‐SLKT in era 2, no differences in patient (P = 0.99), liver graft (P = 0.19), or kidney graft (P = 0.90) survival were observed. In addition, both bilirubin (0.5 versus 0.5 mg/dL; P = 0.86) and creatinine (1.2 versus 1.2 mg/dL; P = 0.68) at last follow‐up were not different between the DCD‐SLKT and DBD‐SLKT patients in era 2. In conclusion, in the most recent era, patients undergoing DCD‐SLKT were able to achieve similar outcomes compared with matched patients undergoing DBD‐SLKT. DCD‐SLKT represents a viable option for appropriately selected recipients.