Liver transplantation (LT) in critically ill patients with chronic liver disease is a high-risk procedure. Recent studies show that the frequency of intensive care unit (ICU) LTs has risen, and outcomes of such transplants have improved significantly. Variation in practices and the impact of center experience with ICU LTs on outcomes is unknown outside of acute liver failure (ALF). This study evaluated the impact of center experience with ICU LT on outcome metrics. Using the United Network for Organ Sharing database, we conducted a retrospective analysis of adult liver transplants performed 2014-2023 in which the patient was in an ICU before transplant, excluding those listed for multiorgan, retransplant, or ALF. Critical care requirements, in-hospital, 1-year, and 3-year mortality, and retransplant were compared by center ICU LT volume quartiles. In total, 9542 ICU LTs were performed across 130 centers (12.8% of total LTs). Over half of U.S. centers performed fewer than 5 ICU LTs per year on average, while the centers in the highest quartile performed nearly two-thirds of all ICU LTs in this period. Utilization of dialysis and of concurrent critical care therapies in ICU LT recipients was higher at high-volume centers ( p <0.05). In-hospital, 1-year, and 3-year mortality for ICU LTs overall were 6.2%, 10.4%, and 23.1%, respectively, with no differences across center volume quartiles (all p >0.05). Adjusting for severity of illness, center volume of ICU LTs in the prior year was associated with a small but significant reduction in 1-year post-ICU LT mortality: aOR 0.96 per 5 ICU LTs ( p <0.001). Expansion of LT for ICU candidates does not appear to threaten center-based metrics and may even offer important benefits to future candidates.

Surgery for bilobar colorectal liver metastasis: from staged resections to liver transplantation. A systematic review of the outcomes of the different strategies.

Coronary artery disease (CAD) is common in liver transplant (LT) recipients, but post-LT rates compared to the general population are unknown in Sweden. We identified all LT recipients in the Swedish National Patient Registry (1987-2020). Each patient was matched with up to 10 population controls for age, sex, municipality, and transplantation year. International Classification of Diseases (ICD) codes defined liver disease aetiology and cardiovascular risk factors. New CAD events were a composite of myocardial infarction, coronary revascularisation, angina, or CAD-related death. Cox regression compared CAD risk in LT recipients and controls across subgroups. We identified 2925 LT recipients and 27,589 controls. Mean age was 54 years; 63% were men. Cardiovascular risk factors were more common in LT recipients. During a median follow-up of 8.0 years, LT recipients had over twice the CAD risk compared with controls (adjusted hazard ratio [aHR]=2.02; 95% confidence interval [CI]=1.80-2.30). Among LT recipients, chronic kidney disease (CKD) (aHR=2.64; 95%CI=1.94-3.60) and previous CAD (aHR=7.85; 95%CI=6.10-10.11) predicted incident CAD. In controls, several factors-including previous CAD, hypertension, diabetes, hypercholesterolemia, CKD, and lung disease-were predictive. The CAD rate was twofold higher in LT recipients than controls. In recipients, only CKD and prior CAD predicted post-transplant CAD, whereas traditional risk factors predicted CAD in controls.

Colorectal dysplasia and malignancy outcomes in primary sclerosing cholangitis and inflammatory bowel disease requiring liver transplantation and colectomy: A multicenter study.

Improving equity and fairness in the referral process for liver transplantation remains a critical unmet need. Multilevel barriers continue to limit timely and appropriate access to liver transplantation evaluation. This study aimed to identify key obstacles to liver transplantation referral and to explore potential strategies to overcome them. An online survey was sent to all centers participating in a Hub-and-Spoke liver transplantation referral network in Northern Italy. The survey addressed barriers related to patient, healthcare system, and practice setting-level factors. Healthcare providers (HCPs) were also asked to rate the perceived usefulness of six proposed actions designed to reduce or prevent referral barriers. A total of 58 responses were collected. Nonadherence, lack of a caregiver, and absence of motivation toward liver transplantation (85%, 82%, and 78%, respectively) were perceived as the most impactful patient-related barriers. Lack of real-time technological communication for data sharing and limited social worker availability were identified as major practice setting-related barrier by 77% and 44.5% HCPs. Lack of knowledge about liver transplantation and unclear indications for liver transplantation were perceived significant healthcare-related barriers by 25% and 21% of HCPs, respectively. All six proposed actions to improve the referral process were rated as clinically impactful by at least 60% of HCPs. Multilevel barriers may still hinder the referral of potential liver transplantation candidates. Implementation of structured psychosocial support and real-time data sharing between centers could significantly reduce inequities in referral to liver transplantation.

Pediatric liver transplant (LT) recipients are at increased risk of developing a food allergy (liver transplantation-associated food allergy [LTFA]). The underlying immune mechanisms are unknown. We evaluated the circulating T- and B-cell subsets and serum cytokine profiles of LT recipients with and without LTFA in a cross-sectional cohort study of 43 LT recipients, 8 of whom had LTFA. The T- and B-lymphocyte subsets were analyzed by flow cytometry, and the serum concentrations of 15 cytokines were measured. For comparison, nontransplanted food allergic controls and healthy controls were recruited. Children with LTFA had increased proportions of newly activated (CD69+) T cells in both CD4+ and CD8+ subsets (P = 0.001 and P < 0.001, respectively), as well as CD4+ T cells of the effector memory CD45RA+ phenotype (P = 0.001), compared with the LT recipients without LTFA. They also had higher serum levels of T helper 2 cytokine interleukin-4 (P = 0.004) and pro-inflammatory cytokines tumor necrosis factor-alpha and tumor necrosis factor-beta (P = 0.007 and P = 0.03, respectively). The corresponding broad immune activation was not noted in the food allergic control group. Notably, the entire cohort of LT recipients exhibited significantly larger proportions of activated, memory, effector, and effector memory CD45RA+ subsets of both CD4+ and CD8+ T cells and higher levels of all the measured cytokines compared with age- and sex-matched healthy control. An overall immune activation is prevalent in pediatric LT recipients, and especially profound in those with LTFA. Since the food allergic state per se may only partly account for this immune profile, the ongoing immune activation might be associated with the susceptibility to develop LTFA.

Liver transplant (LT) recipients are at risk of post-transplant diabetes mellitus (PTDM), and the incidence varies by region. We explored the relationship between county-level food environment and PTDM and whether food insecurity mediates regional variation. First-time LT recipients from July 2004 to December 2022 without pre-existing diabetes were identified in the UNOS SRTR database. Data on 3 measures of healthy food access at the county level were obtained: population experiencing food insecurity, low-income population with low access to grocery stores (food deserts), and ratio of unhealthy to healthy food options (food swamps), all expressed by quartile. The primary endpoint was PTDM. Subdistribution hazard models were used to estimate associations, adjusting for demographic and clinical characteristics and county-level social vulnerability. Mediation analyses quantified the extent to which the food environment explained regional variation in PTDM. A total of 68,273 LT recipients met the inclusion criteria; 15.5% developed PTDM. All 3 food environment measures were independently associated with higher PTDM risk, even after adjustment for recipient, donor, and county-level factors. These measures were also significant mediators of regional variation in PTDM. Food insecurity mediated 48% of regional variation in PTDM, while food deserts and food swamps mediated 20% and 23%, respectively. LT recipients in counties with decreased access to healthy foods were significantly more likely to develop PTDM. Food environment accounted for a meaningful proportion of regional differences in PTDM. Identifying and addressing food insecurity among LT recipients may represent a modifiable pathway to improve long-term outcomes.

Liver transplantation (LT) is the definitive treatment for end-stage liver diseases such as hepatocellular carcinoma (HCC) or cirrhosis, in a clinical context increasingly influenced by the high prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease. Organ shortages have expanded the use of extended-criteria donor grafts, including steatotic livers from donors after brain death or cardiocirculatory death. However, graft steatosis remains a major risk factor for ischemia/reperfusion (I/R) injury, early allograft dysfunction, and posttransplant outcomes, and current protective strategies are insufficient to fully overcome these challenges. Visceral adipose tissue (VAT) is an active endocrine and immunometabolic organ that can shape systemic inflammation and immune tone. Clinical studies report an association between increased VAT and I/R injury, graft dysfunction, rejection, frailty, and HCC recurrence after LT, particularly in recipients with obesity and in recipients transplanted for cirrhosis and/or HCC. Under stress conditions, dysfunctional VAT shifts toward a proinflammatory phenotype characterized by altered secretion of cytokines, adipokines, chemokines, and lipid mediators. This review analyzes the role of the adipose tissue-liver axis in LT, with emphasis on how adipose-related mediators may modulate I/R injury and alloimmune responses in clinically relevant settings. We synthesize evidence from human cohorts and preclinical LT and warm I/R models, highlight major knowledge gaps related to tissue-source attribution and context-dependent mechanisms, and discuss emerging therapeutic strategies to modulate adipose tissue inflammation and immunometabolic signaling. Integrating adipose biology into LT research may help refine risk stratification and identify new avenues to improve graft utilization and long-term outcomes.

To describe the trend of indications and outcomes of Liver transplant (LT) for Inherited Metabolic Disorders (IMD) in a single centre over 30 years. A retrospective review of LT undertaken for IMD between 1989 to 2021 wasperformed. Demographic and clinical data, including LT indications, complications and outcomes, were collected. Categorical data were described as proportions; Kaplan-Meier analysis was used to determine patient/graft outcomes. 55 patients (29 females) underwent 62 transplants between 1989 to 2021. Postoperative complications were rejection (17/62; 27.4%), bile leak (5/62; 8%), primary non-function (4/62; 6.5%), hepatic artery thrombosis (6/62; 9.7%) and portal vein thrombosis (1/62; 1.6%). Mortality rate was highest in organic acidaemia (7/11 or 63.6%) in the 1st 2 decades of this period. Mortality was higher in the first decade of our LT program, which improved in subsequent decades. There was 53.3% mortality from 1989 to 2000; 18.8% from 2001 to 2010; and 8.3% from 2011 to 2021. Cumulative 1-, 5-, and 10-year patient survival rates since 1989 were 78.1%,76.3%, 74.5%; graft survival rates were 69.3%,67.7% and 66.1%, respectively. Although our overall patient and graft survival rates are lower than global reports, outcomes have improved in the last decade with careful patient and donor selection and changes in LT protocol.

Diagnostic accuracy of donor-derived cell-free DNA for rejection following liver transplantation: a systematic review and meta-analysis.

Limited information on the business practices of liver transplant (LT) centers worldwide has been published. Characterizing this data could help identify best practices as well as opportunities for improvement. As such, the International Liver Transplant Society (ILTS) Business Practice Committee conducted a global online survey of LT centers, which was sent to the ILTS membership. Questions focused on 5 main domains: transplant practice and volumes, workforce, finances, quality assessment and performance improvement, and overall program function. Data was compared across program geographic regions and transplant volume. A total of 89 discrete centers were represented, of which 76.4% were academic/university-affiliated, and about one-third each were from Europe (36.0%) and North America (31.5%). The top 3 problems programs reported were finances/funding (60.7%), adequate program support/guidance (48.3%), and transplant volumes (43.8%). In all, 59.6% of respondents felt their salary was undercompensated, consistent across geographic regions. In addition, 69.7% felt their center was not adequately funded to meet program goals, with programs in Europe (N=28/32, 87.5%) and Oceania (N=2/3, 66.7%) most impacted. Transplant surgeon retainment was noted as more difficult for lower volume programs (<50 liver transplants/year, N=13/31). Nearly half (42.7%) of all programs felt under-resourced to provide high-quality care, and the majority (80.9%) felt there was room for growth and improvement under their current model. While international concerns varied widely among LT centers, inadequate salary and center funding, low transplant and referral volumes, and staff retainment were persistent themes. Focusing on adopting region-specific best practices and developing transplant systems of care that focus on these elements is critical to provide optimal care to LT patients worldwide.

Controlled donation after circulatory death (cDCD) increases graft availability but may carry higher perioperative risk, which in situ normothermic regional perfusion (NRP) may mitigate by reducing ischemia-reperfusion injury. Evidence remains limited regarding NRP impact on PRS during liver transplantation (LT). The objective of this study was to compare the incidence of PRS and early postoperative outcomes between cDCD LT with NRP and donation after brain death (DBD) LT. This was a retrospective, single-center observational study comparing cDCD LT with NRP versus DBD LT. The primary endpoint was PRS (≥30% mean arterial pressure decrease for ≥1 min within 5 min of reperfusion). Secondary endpoints included early allograft dysfunction, acute kidney injury (AKI), rejection, biliary/vascular complications, and survival. Associations between graft type and outcomes were assessed using logistic regression (binary) and linear regression (continuous), and Cox models (time-to-event), with multivariable adjustment for clinically relevant covariates. Among 106 recipients (cDCD n = 47; DBD n = 59), PRS occurred 27 patients (25.5% versus 25.4%). Graft type was not associated with PRS after adjustment (odds ratio, 1.13; 95% confidence interval, 0.41-3.10; P = 0.81). No significant differences were observed in early allograft dysfunction, acute rejection, AKI, or biliary and vascular complications. There was 1 death in the cDCD group and 5 in the DBD group (2.1% versus 8.5%). In a standardized program using routine NRP, cDCD LT did not increase PRS risk and achieved early outcomes comparable to DBD LT. These findings suggest clinical feasibility and short-term safety of Maastricht III protocols incorporating NRP.

Identifying an optimally matched donor is a critical determinant of outcomes following liver transplantation (LT). Several donor- and recipient-related factors have been shown to influence posttransplant survival. However, the impact of donor-recipient sex mismatch (DRSM) on long-term outcomes remains controversial, with inconsistent findings reported across prior studies. This study aimed to further clarify the contemporary role of DRSM in LT outcomes. We conducted a single-center retrospective cohort study including 1146 adult patients who underwent LT at the Ajmera Transplant Centre, Toronto, between January 2014 and January 2022. Donor and recipient characteristics, including age, sex, and donor type, were analyzed. The primary outcome was patient survival up to 10 y of follow-up. Comparative analyses were performed between recipients with mismatch (DRSM+) and those without (DRSM-), as well as relevant subgroup analyses. In unadjusted survival analysis, recipients in the DRSM+ group demonstrated slightly higher survival compared with DRSM- recipients up to 10 y following LT (P = 0.018). However, after multivariable adjustment and propensity score matching, survival was comparable between groups, and DRSM was not identified as an independent predictor of mortality. Subgroup analyses showed no adverse effect of DRSM in deceased donor transplantation (P = 0.547), while a survival difference was observed in the living donor cohort (P < 0.001). In addition, female recipients exhibited improved survival compared with male recipients, irrespective of DRSM. DRSM does not appear to be an independent risk factor for reduced long-term survival after LT. Moreover, the composition of favorable recipient and donor characteristics seems to be the main factors influencing long-term survival. These findings suggest that DRSM alone should not preclude donor selection in clinical practice.

Following therapeutic advancements, recompensation has gained increasing recognition in patients on waitlist for liver transplantation (LT). Identifying key predictors of waitlist removal because of improvement can enhance prognostication and resource allocation. We hence examined predictors of improvement-related waitlist removal using a machine learning-based approach with data from the United Network for Organ Sharing database. In this retrospective cohort study, adult LT waitlist candidates from 2000 to 2025 in the United Network for Organ Sharing registry were included. A random survival forest model was applied to examine key predictors associated with improvement-related waitlist removal, while accounting for death and LT as competing risks. Variable importance (VIMP) measure and minimal depth were used to guide variable selection. Model performance was evaluated using the concordance index, Brier scores, and time-dependent area under the curve. The cohort included 127 978 individuals listed for LT. Eight thousand four hundred ninety-three (6.6%) were delisted because of clinical improvement. The random survival forest model demonstrated strong performance and discriminatory ability overall at 1, 5, and 15 y (concordance index was 0.777, 0.771, and 0.781; time-dependent area under the curve was 0.78, 0.78, and 0.80). Brier scores were reduced relative to the reference. Strong predictors of recovery highlighted in both VIMP and minimal depth-based assessments of VIMP included diagnosis, age, and serum albumin. Identified variables could inform the development of robust predictive models to guide individualized decision-making for LT. With further validation and integration into clinical workflows, such models could enhance prognostication of patient trajectory on the LT waitlist and facilitate appropriate resource allocation.

Liver transplantation remains the treatment of choice for hepatopulmonary syndrome (HPS) with severe hypoxemia, but portopulmonary hypertension (PoPH) has traditionally been viewed as a contraindication to liver transplantation owing to its frequent posttransplant deterioration. We describe here the sequential presence of both pulmonary vascular disorders in a cirrhotic patient in the pretransplant period. Liver transplantation was made possible following effective management of pulmonary hypertension, with favorable outcome 3 years post-liver transplantation. Finally, our case report and literature review suggest that the coexistence of HPS and PoPH in patients with advanced liver disease could be more common than previously recognized.

2025 Clinical Update in Liver Transplantation.

To investigate the prevalence of inflammatory bowel disease (IBD) in a cohort of Brazilian patients with primary sclerosing cholangitis (PSC) and evaluate clinical and prognostic factors associated with concomitant IBD. IBD is reported worldwide in 62% to 81% of patients with PSC, especially in males and north Europeans. Little is known about the association of IBD and PSC in population from multigenetic ethnic origin. Data of PSC patients from the Brazilian Cholestasis Study Group database were retrospectively reviewed to compare demographic, clinical, laboratory, and transplant-free survival between those with and without IBD. After exclusion of 59 (14%) participants with overlap syndrome with autoimmune hepatitis, 359 individuals with PSC were included {56% male, median age 44 [interquartile range (IQR): 33 to 54] y}. IBD was investigated in 298 (83%) participants and diagnosed in 217 (73%), including ulcerative colitis (83%), Crohn's disease (13%), and indeterminate colitis (4%). Male sex frequency was similar in patients with and without IBD (58% vs. 47%, P =0.073). IBD was more frequently diagnosed in patients without obesity ( P =0.035), positive for antinuclear antibody ( P =0.006), and positive for anti-smooth muscle antibody ( P =0.046). IBD diagnosis occurred before, concomitant, or after PSC diagnosis in 59%, 22%, and 19% of cases, respectively. IBD was more frequently diagnosed before PSC in participants asymptomatic for liver disease ( P =0.017), without advanced liver disease ( P =0.017), before liver transplantation (LT) ( P <0.001), and positive for antinuclear antibody ( P =0.021). In a median follow-up of 69 months (IQR 31-124), LT occurred in 27.7% and cohort mortality was 11.4%. IBD was neither associated with the combined outcome of death or LT ( P =0.745) nor with transplant-free survival ( P =0.902). In Brazilian PSC patients, IBD frequency was similar to that reported in other populations but exhibited a balanced proportion between males and females. IBD diagnosis occurred before PSC in most patients, especially those without advanced liver disease. IBD presence was not associated with worse PSC prognosis.

The financial impact of chronic liver disease among adults undergoing liver transplant (LT) evaluation remains understudied. We performed a cross-sectional multicenter study to explore high financial burden, defined as medical out-of-pocket expenses ≥10% of income (per prior literature), among adult LT candidates. We aimed to identify associations between high financial burden and (1) work productivity impairment; (2) financial distress (material, behavioral, and psychological consequences of financial burden); (3) financial toxicity (health-related quality of life, HRQOL). From May 2023 to April 2024, 453 patients from 13 United States transplant centers were included. Patients completed questionnaires assessing financial burden, financial distress, financial toxicity (EuroQol EQ-5D-5L instrument), and work productivity and impairment (Work Productivity and Activity Impairment Questionnaire: Specific Health Problem Version). Among LT candidates, 23.3% reported a high financial burden, and only 27.6% were employed. High financial burden was associated with a higher rate of absenteeism from work (34.1% vs. 16.9%, p=0.018) among employed participants. In adjusted models, high financial burden was significantly associated with inability to pay for basic necessities (aOR 4.76, 95% CI: 2.34-9.67), delayed or foregone medical care (aOR 4.02, 95% CI: 2.30-7.02), and psychological distress (aOR 4.63, 95% CI: 1.95-10.98) but was not associated with HRQOL (EQ-5D β: -0.04, 95% CI: -0.08 to 0.00; EQ-5D-VAS β: -4.53, 95% CI: -10.1 to 1.02). These results highlight the critical importance of implementing routine screening for financial burden in this high-risk population and developing strategies to mitigate associated adverse outcomes.

Analysis of risk factors for mortality in patients with mushroom poisoning-induced hepatic failure.

Robotic recipient liver transplantation worldwide: a systematic review and meta-analysis of the first 93 patients, from feasibility to early outcomes.