Schisandrin B alleviates liver allograft rejection by stabilizing ACOD1 in Kupffer cells to potentiate itaconate-NRF2-mediated suppression of CD8+ T cell chemotaxis.

Pre-Transplant Circulating cTfh17 and Donor-Reactive T Follicular Helper Responses Distinguish Liver Transplant Recipients Who Develop Ischemia-Reperfusion Injury and Donor-Specific Antibody.

Hepatic artery thrombosis (HAT) is a severe and potentially graft-threatening complication after liver transplantation, associated with biliary ischemia, graft failure, and high mortality. We report the case of a 43-year-old woman with primary sclerosing cholangitis who developed early HAT after orthotopic liver transplantation. An initial endovascular recanalization attempt was unsuccessful, and progressive ischemic cholangiopathy required liver color Doppler with aorto-hepatic arterial reconstruction. During follow-up, recurrent hepatic artery graft thrombosis was detected. Given the high surgical risk, an endovascular approach was undertaken. Successful intraluminal recanalization was achieved using percutaneous transluminal angioplasty and balloon-expandable stent placement, resulting in restoration of hepatic arterial flow. Follow-up imaging confirmed sustained graft patency and preserved liver perfusion. This case highlights the role of timely endovascular intervention as a viable graft-saving option in selected patientswith complex post-transplant HAT.

BACKGROUND Despite improvements in technical and pharmacological expertise, orthotopic liver transplantation (OLT) still leads to potentially serious neurological complications (NCs) with very strong implications for graft survival, functional outcomes, and mortality. MATERIAL AND METHODS We conducted a retrospective study with the aim of defining the incidence, etiology, and clinical features of early post-OLT NCs, and we searched for preoperative, intraoperative and postoperative risk factors associated with their occurrence. RESULTS Among 376 patients who underwent OLT, 97 (25.8%) had at least 1 neurological manifestation and 24 (6.38%) had more than 1 neurological manifestation. Delirium/metabolic encephalopathy was the most frequent (14.1%), followed by seizures (3.7%) and clinical manifestations of neurotoxicity (3.7%), and then by osmotic demyelination syndrome and peripheral nervous system injury (2.9%). NCs were the cause of death in 9/97 patients, and 11 patients had severe sequelae. Having NCs was correlated with more severe liver disease, a history of chronic renal impairment, higher plasma sodium concentrations at postoperative day 2, higher perioperative delta sodium, and a higher probability of having postoperative acute renal impairment, postoperative infections, graft rejection, and more than 3 systemic complications. No preoperative neurological comorbidities were found to be risk factors for developing acute NCs early after OLT. Patients with NCs had worse outcomes: longer in-hospital length of stay, longer intensive care unit (ICU) stay, higher probability of ICU re-admission, higher probability of in-hospital death, and higher probability of needing rehabilitation after hospital discharge. CONCLUSIONS Understanding the pathophysiology of NCs after OLT may lead to the development of prevention strategies for often untreatable neurological diseases.

Drug-induced liver injury (DILI) is associated with high mortality risk. However, no biomarker can reliably predict outcome. In order to identify baseline parameters that are associated with mortality the data of 268 prospectively collected DILI patients were analyzed. Multivariate logistic regression and receiver operating characteristic curves were used to identify the parameters being most predictive for a fatal outcome, as defined by orthotopic liver transplantation (OLT) or death. 10.4% of patients had a fatal outcome, which was associated with higher levels of transaminases, total bilirubin, INR and model for end-stage liver disease (MELD) scores (25 vs. 12, p < 0.001). Multivariate analysis revealed that only MELD and aspartate aminotransferase (AST) were independently associated with a poor outcome, the MELD score in particular had an extraordinarily high c-statistic of 0.93 (95% CI: 0.87-0.97). At a cut-off of ≥ 20, MELD could predict a fatal outcome with a sensitivity and specificity of 88% and 81%. The predictive performance of the MELD score could even be enhanced by combing it with AST elevation: At a cut-off of ≥ 20 and ≥ 29.6xULN, respectively, positive and negative predictive values of 44% and 96% were observed, which were higher than for any other baseline parameter.

WCN26-6504 SHORT-TERM EFFICACY AND LONG-TERM FOLLOW-UP OBSERVATION OF ROXADUSTAT IN TREATING RENAL ANEMIA iN ELDERLY PATITENTS WITH NDD-CKD

Biliary non-anastomotic strictures (NAS) are among the most severe complications of liver transplantation (LT). Risk factors include donation after circulatory death (DCD) as compared to donation after brain death (DBD) and prolonged ischemia times. Immunological factors are also believed to play a role, as ABO blood group incompatibility is associated with NAS. This study aimed to assess the effect of rhesus (Rh) antagonism (RhA) on development of NAS after LT. All 678 orthotopic LTs performed at the LUMC between January 2000 and August 2023 (DBD = 422, DCD = 191, and machine perfused = 65) were included in this observational cohort study. Data were locked on October 1st, 2023. The primary endpoint was NAS that required cholangiographic intervention. RhA was defined as a Rh negative recipient receiving a Rh positive donor graft. Kaplan-Meier curves and Cox regression models were used for survival and risk factor analysis. Immunohistochemistry and Western blot were performed on human biliary tissue to assess the presence of the RhD antigen on biliary epithelial cells. Total incidence of NAS was 142 (20.9%), of which 14.9% for DBD, 35.6% for DCD, and 16.9% for machine-perfused grafts (p < 0.001). RhA was identified in 52 (7.7%) cases. In LTs with DBD, RhA was associated with higher incidence of NAS (HR 2.70; 95% CI = 1.41-5.19). This effect was absent in the overall cohort and in LTs with DCD specifically. No expression of RhD on biliary epithelium was found. RhA was associated with a threefold risk of NAS development after LT with DBD.

WCN26-6442 CHARACTERISTICS OF RECIPIENTS OF ORTHOTOPIC LIVER TRANSPLANTS (OLT) AND SIMULTANEOUS LIVER AND KIDNEY TRANSPLANTS (SLKT) - ETIOLOGY, DEMOGRAPHIC PROFILE, AND SIGNIFICANCE OF MULTIPLE ETIOLOGIES

Hepatocyte transplantation (HTx) offers a safer, less invasive alternative to orthotopic liver transplantation for inherited metabolic liver diseases, especially in high-risk pediatric patients. Combining HTx with ex vivo gene editing is a promising autologous therapeutic strategy using the patient's cells. We investigated the feasibility of this approach by applying CRISPR-Cas9 gene knock-out to neonatal mouse hepatocytes and comparing their engraftment potential with that of mature adult cells in the Fah-/- mouse model of hereditary tyrosinemia type I (HT1). Electroporation-mediated gene editing did not significantly impair the ability of neonatal hepatocytes to engraft invivo. Quantitative histological analysis revealed comparable liver repopulation levels between recipients of gene-edited neonatal cells and adult cells after hepatoxicity-mediated selection, providing a benchmark for electroporation-mediated gene editing in neonatal hepatocytes, and supporting the development of genetically corrected neonatal hepatocyte products as a crucial long-term or bridge-to-transplant therapeutic strategy for pediatric liver disease.

Background: Acute kidney injury (AKI) is common after orthotopic liver transplantation (OLT). In major surgery, anemia has been associated with postoperative AKI. Although patients undergoing OLT frequently suffer from anemia, its impact on postoperative AKI remains unclear. We performed a single-center retrospective study including 724 patients undergoing their first OLT between January 2004 and December 2019 at the Medical University of Vienna. We evaluated whether perioperative hemoglobin concentrations were associated with postoperative AKI, renal replacement therapy, or mortality. Preoperative hemoglobin concentrations were 10.9 ( ± 2.1) g/dL in patients with AKI after OLT and 11.5 ( ± 2.1) g/dL in those without. Higher preoperative hemoglobin concentrations were associated with a lower probability of AKI (OR 0.847; P < 0.001) and a decreased probability of developing a higher AKI stage (OR: 0.895; P = 0.002). Stage 3 AKI was associated with increased 1-year (OR: 1.909; P < 0.001) and overall mortality (HR: 1.420; P = 0.037). Higher nadir hemoglobin concentrations within 48 h after OLT were associated with a lower probability of AKI (OR: 0.806; P = 0.033) and a decreased probability of developing a higher AKI stage (OR: 0.782; P < 0.001). In conclusion, higher perioperative hemoglobin concentrations were associated with a lower probability of AKI after OLT. Severe AKI was associated with an increased mortality.

BACKGROUND Incisional hernia (IH) is a common late complication following orthotopic liver transplantation, with reported incidences up to 46%. Incision type, particularly the use of the Mercedes incision, has been implicated as a modifiable risk factor due to its midline component and associated fascial disruption. AIM To determine whether the Mercedes incision increases the risk of IH compared with Chevron and J-shaped incisions in adult liver transplant recipients. METHODS We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines (PROSPERO: CRD42020161632). PubMed, MEDLINE, EMBASE, Google Scholar, and Cochrane Library were searched up to June 2025 for studies reporting IH incidence stratified by incision type. Observational studies with ≥ 12 months follow-up in adults were included. Random-effects meta-analysis was performed to estimate pooled odds ratios (OR) with 95%CI. Heterogeneity was assessed using the I ² statistic. Exploratory subgroup analyses examined closure technique, incision closure approach, and suture material. RESULTS Eight observational studies (n = 2965) met the inclusion criteria. Pooled analysis showed the Mercedes incision was associated with a higher IH risk compared with Chevron or J-shaped incisions (OR = 1.93, 95%CI: 1.06–3.51; I ² = 76%). Sensitivity analysis excluding a zero-event study reduced the OR to 1.79 (95%CI: 0.99–3.25). Single-layer closure (OR = 3.75, 95%CI: 2.22–6.35) and absorbable sutures (OR = 3.06, 95%CI: 1.18–7.93) were associated with increased IH rates in exploratory analyses. CONCLUSION The Mercedes incision is likely associated with a higher risk of IH after liver transplantation compared with Chevron or J-shaped incisions. Surgical planning should consider incision type alongside patient and technical factors to reduce long-term abdominal wall morbidity.

Background. In unresectable hepatoblastoma (HB), particularly “pre-treatment extent of tumor” (PRETEXT) IV tumors or those with positive annotation factors, standard management consists of intensive chemotherapy followed by surgical resection or orthotopic liver transplantation (OLT). Radiotherapy has traditionally been avoided because of the liver’s radiosensitivity and the risk of radiation-induced liver disease. Proton beam therapy (PBT), owing to its dosimetric advantage and ability to spare uninvolved liver parenchyma, may represent a potential local control strategy in selected pediatric patients for whom curative surgery or OLT is not feasible. Case Presentation. We describe five pediatric patients with advanced hepatoblastoma treated with proton beam therapy at our institution between February 2022 and January 2024. The cohort included three girls and two boys, with a median age of 3.0 years (interquartile range [IQR], 1.6–4.0) and a median alpha-fetoprotein level of 435,453 ng/mL (IQR: 7,668–1,276,681) at diagnosis. All patients were initially considered inoperable because of extensive hepatic involvement, inadequate future liver remnant, or multifocal disease, and OLT was not feasible owing to donor limitations or medical comorbidities. All received neoadjuvant chemotherapy using SIOPEL-based regimens, achieving partial tumor response. Tumors ranged from 5 to 12 cm and involved central hepatic segments, the portal region, or both lobes. PBT was delivered at a total dose of 50 GyE in 10–25 fractions as definitive or consolidative therapy, followed by surgical resection in three patients. Two patients additionally received targeted therapy and immunotherapy. At last follow-up, four patients were alive with no evidence of disease, while one patient died from tumor progression. Conclusions. These cases suggest that proton beam therapy may serve as a feasible liver-sparing local treatment option for selected pediatric patients with unresectable or residual hepatoblastoma when surgery or OLT is not possible. While limited by availability and cost, PBT may facilitate multimodal therapy and preserve future treatment options.

The health burden of end-stage liver disease continues to grow, and orthotopic liver transplantation remains the only curative treatment. Three-dimensional (3D) culture systems support the in vitro culture of primary liver cells, allowing them to recapitulate native tissue architecture. This technology holds considerable potential for regenerative medicine and disease modeling. However, the practical application of liver organoid (LO) technology is hindered by the inherent limitations of LOs derived from single-tissue sources. In this study, we integrated human umbilical cord mesenchymal stromal cells (hUC-MSCs) into single-source LOs and assessed their effects on organoid formation and function. During the expansion phase, co-culture with hUC-MSCs yielded a 2-fold increase in organoid number compared to LOs cultured alone, although no significant changes were observed in the expression of genes related to organoid lifespan. Liver-specific functions of LOs after 7 day incubated with differentiation medium were further investigated. Despite constructing organoids from mature hepatocytes, co-culture with MSCs promoted non-hepatocyte differentiation, as evidenced by the expression of the cholangiocyte organoid marker cytokeratin 19. Furthermore, LOs co-culture with hUC-MSCs demonstrated increased albumin and urea secretion. In contrast, glucose consumption and ammonia clearance rates showed no significant differences. Following in vivo transplantation, serum biochemical markers normalized in both transplanted and control groups. However, histological analysis revealed superior liver tissue repair in the transplanted group. Our findings indicate that MSCs positively enhance the proliferative capacity of LOs and confer limited functional benefits, and incorporation of MSCs may promote non-hepatic cell differentiation. This effect was particularly evident within the extracellular matrix components of the hydrogel culture system.

Application of the novel peroral choledochoscope in hepatolithiasis after liver transplantationVideo 1 Hepatolithiasis removal after liver transplantation with the eye-Max choledochoscope. Fig. 1 a In a 58-year-old man with a history of intermittent right upper abdominal pain after orthotopic liver transplantation, magnetic reso- nance cholangiopancreatography revealed a focal stenosis of the hilar bile duct and dilation of the left intrahepatic bile ducts.b The peroral choledochoscope was advanced into the left intrahepatic bile duct, revealing a dark brown stone.c Under direct visualization, the stone was grasped and pulled into the duodenum.

Simultaneous robotic off-pump coronary artery bypass and orthotopic liver transplantation in a Child-Pugh C patient: an operative playbook.

Approximately 1-7% of patients develop persistent lymphatic ascites after liver transplantation. This study describes the diagnosis and treatment of lymphatic ascites in patients post liver transplantation, refractory to conservative therapy. A review of the prospectively collected database was conducted to identify patients who received interventions for persistent lymphatic ascites following liver transplantation. Patient demographics, baseline characteristics, imaging findings, procedural details, and follow-up information were gathered. Four adult patients after orthotopic liver transplantation with chylous ascites (CA) and 4 pediatric patients after split liver transplantation with hepatic lymphorrhea (HL) were included in this study. CA patients were characterized by elevated triglycerides (1010mg/dL, 442-1769), and HL patients were characterized by low serum albumin ascites gradient (SAAG < 1.1) and low triglycerides. In 3/4 patients with CA, dynamic contrast MR lymphangiography and intranodal lymphangiography demonstrated obstruction of the central lymphatic system. The mesenteric lymphatics were then embolized with either n-BCA glue or lipiodol. One-fourth patients had stenosis of the portal vein anastomosis, which was balloon dilated using a transjugular approach. All 4 patients reached resolution of ascites at a median of 27days. In 3/4 patients presenting with HL, liver lymphangiography demonstrated extravasation of the contrast. That was embolized with either glue or lipiodol. One-fourth patient demonstrated no extravasation but significant lymphangiectasia. In all patients, there was a resolution of ascites at a median of 14days after intervention. Three mechanisms of post-transplantation lymphatic ascites were identified: portal venous hypertension due to iatrogenic obstruction; obstruction of central lymphatics resulting in congestion of the mesenteric lymphatic system and mesenteric lymphatic leak; and liver lymphorrhea. Identification of the mechanism of ascites allowed for successful percutaneous treatment in all patients.

Case Report: Intra-abdominal Mucormycosis Diagnosed at the Time of Liver Transplantation for Surgically Induced Acute Liver Failure.

Golgi protein 73 (GP73) is typically expressed in biliary epithelial cells and is minimally present in healthy hepatocytes. In hepatocellular carcinoma (HCC), GP73 serum levels are often elevated, although this increase may be due to the presence of cirrhosis. Alpha-fetoprotein (AFP) remains the most widely used biomarker for HCC clinical diagnosis, yet its sensitivity and specificity are limited. GP73 has emerged as a potential novel biomarker and therapeutic target for HCC disease. Here we report about a 55-year-old male with hepatitis C virus (HCV)-related cirrhosis and HCC, referred for orthotopic liver transplantation (OLT) in 2023. Retrospective laboratory analysis showed elevated levels of AFP, liver enzymes, and GP73, with the latter reaching 123 ng/mL (reference interval 4-40), even post-transplantation during tacrolimus-based immunosuppressive therapy. Research findings on GP73 dynamics postsurgery remain inconsistent, with some reporting normalization and others, as in our case, showing persistent elevation. The pathophysiological role of GP73 is still not fully elucidated; further research is needed to determine its potential as a biomarker for disease monitoring and therapeutic response in HCC.

Introduction: Invasive fungal infections are a major source of morbidity and mortality after liver transplantation. Candida auris and Mucorales species pose distinct challenges, including drug resistance, delayed diagnosis, and limited treatment options. Fosmanogepix, a novel antifungal targeting the fungal enzyme Gwt1, is under investigation for multidrug resistant infections. We present a rare case of drug-resistant Candida auris (C. auris) and Mucor circinelloides (M. circinelloides) bloodstream and intraabdominal infection after liver transplant treated with the novel antifungal agent fosmanogepix. Description: A 52-year-old man with metabolic dysfunction-associated steatotic liver disease and alcoholic cirrhosis underwent orthotopic liver transplantation complicated by primary graft nonfunction, requiring retransplantation. His postoperative course was further complicated by a persistent abdominal wall infection involving drug-resistant C. auris and M. circinelloides, unresponsive to amphotericin B, micafungin, and posaconazole. Infection was suspected to be associated with retained Gore-Tex mesh. He also developed respiratory failure requiring tracheostomy. After six weeks of ineffective antifungal therapy, fosmanogepix was initiated under expanded access. Within 18 days, beta-D-glucan levels decreased from 204 to 121 pg/mL, and cultures confirmed susceptibility to fosmanogepix. Following clinical improvement, he transitioned to a prolonged course of amphotericin B. This case highlights a rare use of fosmanogepix in a liver transplant patient with concurrent drug-resistant fungal infection. Discussion: Although a single case cannot establish efficacy, the rarity of concurrent C. auris and M. circinelloides infection in a liver transplant recipient and the increasing prevalence of multidrug resistant fungal pathogens support the need to highlight emerging therapies. This patient failed conventional treatment and showed clinical improvement and microbiologic response after fosmanogepix was initiated under expanded access. The observed decline in beta-D-glucan and transition to oral therapy contributed to infection control and stabilization. Fosmanogepix may provide a much-needed alternative for transplant recipients with multidrug resistant fungal infections unresponsive to existing therapies.

For liver transplant candidates, trans-plantation or death on wait lists can be competing risks. This study used competing risk analysis to estimate the probability of death among patients on wait lists for liver transplant. We retrospectively analyzed liver transplant candidates registered at the Montaseriyeh Transplant Center Registry of Mashhad University of Medical Sciences (Iran) from 2013 to 2024. We followed patients from listing through transplant, death, or end of study. We collected demographic, clinical, laboratory, and follow-up details. We used Gray's test to assess cumulative incidence of death across different listing periods, orthotopic liver transplant groups, and Model for End -Stage Liver Disease severity levels. To estimate the effects of various covariates while accounting for transplantation as a competing event, we conducted a competing risk regression using the Fine and Gray subdistribution hazard model. We used R software (cmprsk and cuminc packages ) for statistical analyses. Average age of patients was 50.84 ± 13.78 years. Over the follow-up period, 503 patients (60.0 % ) received transplants, 233 (27.8 % ) died while waiting for transplant, and 102 (12.2 % ) were administratively censored. Among transplant patients, 65.9% had Model for End-Stage Liver Disease scores between 10 and 20, with mortality increasing with increased scores. The hazard model showed no significant differences in death risk by age, sex, marital status, year of transplant, or etiology group. However, patients with higher Model for End-Stage Liver Disease scores had significantly greater risk of death than those with lower scores (P < .001 ). Increased Model for End -Stage Liver Disease score emerged as the most significant predictor of mortality among patients waiting for liver transplant. Focusing on candidates with high scores and tackling socioeconomic barriers could improve survival outcomes. These insights can inform future approaches to optimize patient prioritization and transplant allocation.