Children with advanced hepatoblastoma (PRETEXT III-IV) often require complex surgical decision-making; however, contemporary data describing long-term outcomes and recurrence patterns across the full spectrum of definitive surgery remain limited. We included 68 patients with PRETEXT III and IV who underwent definitive liver resection (LR, n=41) or liver transplantation (LT, n=27). The primary objective of this study was to characterize survival and recurrence patterns after surgical clearance of primary liver disease. The median age at diagnosis was 18 months (IQR, 9-36). All the patients received neoadjuvant chemotherapy. With a median follow-up of 62 months (IQR, 25-146), 5-year overall survival was 79% (95% CI: 65% - 97%) after LT and 88% (95% CI 78%-100%) after LR. After LT, recurrence occurred in 6 of the 27 (22%) patients, including isolated lung metastases (n=4), combined lung-graft involvement (n=1), and isolated graft relapse (n=1). Recurrence occurred in 6 of the 41 patients (15%) after LR, involving the liver (n=2), lung (n=2), combined liver and pulmonary disease progression (n=1) and unspecified site (n=1). Among LR patients with residual pulmonary nodules at surgery (n=8), progression occurred in three, two of whom died. The majority of events occurred within the first postoperative year after LR or LT. All deaths (n=10, 15%) were attributable to tumor recurrence or progression of known lung metastasis, including all post-LT recurrences. There were no perioperative or graft-related deaths. Univariate analysis showed that a serum alpha-fetoprotein decline of less than 95% and distant metastasis at diagnosis were associated with poor prognosis after LT and LR. Mortality in this cohort was entirely disease-related, occurring after recurrence or progression of residual metastases rather than from surgical modality. Incorporating AFP trend, pulmonary response, and detailed imaging into preoperative assessment may help identify high-risk patients and support more informed surgical decision-making.

Return to alcohol use after liver transplantation is a major clinical challenge, with limited structured approaches for prevention and management in the post-transplant setting. To address gaps in post-transplant alcohol use disorder (AUD) care, we established the Long-term Individualized Follow-up after Transplant (LIFT) Clinic, a co-located multidisciplinary program integrating hepatology, psychiatry, social work, and health navigation. We conducted a retrospective cohort study of 113 patients referred between December 2022 and December 2024. Fifty patients attended at least one clinic visit, including 25 referred for prevention and 25 for management. Patients were followed longitudinally as part of routine post-transplant care. Among patients in the prevention track, the median time to first visit was 4.2 months post-transplant, 56% received medications for AUD, and one patient (4%) experienced two brief episodes of return to alcohol use. Among patients in the management track, 84% received medications for AUD; at the end of follow-up, 28% achieved sobriety, 60% reduced alcohol use, and 12% showed no reduction. Early implementation challenges included high non-attendance, which improved following operational changes. These findings demonstrate the successful implementation of a patient-centered, integrated care model for managing AUD after liver transplantation while highlighting patient engagement as an important early implementation challenge and provide a practical model for multidisciplinary post-transplant AUD care at other transplant centers.

Early liver transplantation (LT) is increasingly being adopted as a treatment for alcohol-associated hepatitis (AAH), but the optimal strategy for incorporating AAH into the existing organ allocation framework remains unclear. This retrospective cohort study used the United Network for Organ Sharing database (1/1/2018-12/31/2024) to compare adults waitlisted for first-time, single-organ LT for AAH against other alcohol-associated liver disease (ALD) and non-ALD. During the study period, waitlisting and LT for AAH increased more than six-fold, with 98.2% of centers performing LT for this indication. Compared to other ALD and non-ALD, patients with AAH experienced lower waitlist mortality (8.2% vs. 12.6% and 19.3%, respectively; p<0.001) and higher LT rates (81.2% vs. 69.0% and 67.0%, respectively; p<0.001). After adjusting for clinical and demographic characteristics on initial waitlist application, both other ALD and non-ALD were associated with higher waitlist mortality relative to AAH (adjusted hazard ratio [aHR]=1.23 with p=0.003 and aHR=1.86 with p<0.001, respectively). Among patients with AAH, waitlist mortality was not associated with MELD scores <40 (p=0.66). Across all MELD categories, non-ALD was associated with higher waitlist mortality than AAH (HR 1.83-3.23; all p≤0.005), while other ALD was associated with higher mortality at most MELD strata (p<0.05 at MELD 20-24 and ≥30). Of individual MELD components, serum sodium was not associated with AAH waitlist mortality (HR=1.01; p=0.53), while INR was a stronger predictor of mortality in AAH than other LT indications (HR=1.95 for AAH vs. HR=1.14 for other ALD vs. HR=1.23 for non-ALD; all p<0.001). Patients with AAH are disproportionately prioritized under the current organ allocation system, underscoring the need to revise allocation practices to ensure equitable LT access.

The liver is a highly spatially organized organ in which microanatomy underpins metabolism, immune regulation, and regenerative capacity. In liver transplantation, spatially defined processes, including ischemia reperfusion injury (IRI), alloimmune activation, and disease recurrence critically shape graft function and long-term outcomes. However, conventional bulk and single-cell transcriptomics and proteomics approaches lack the ability to resolve these events within their native tissue context. Recent advances in spatial transcriptomic and proteomic technologies enable high-resolution mapping of cellular interactions within healthy tissue, providing new insight into the microenvironmental niches that drive graft injury and repair. This review summarizes current spatial omics platforms, including sequencing-based, imaging-based, and microdissection approaches, with emphasis on technical and analytic considerations relevant to transplantation. It synthesizes emerging applications in key transplant settings, including IRI, machine perfusion-mediated graft reconditioning, alloimmune injury, chronic remodelling, and recurrent liver disease. Spatial studies demonstrate that liver graft injury arises within discrete immune-stromal-parenchymal niches that influence progression toward recovery or chronic dysfunction. Translation into clinical practice will require longitudinal sampling and harmonized workflows, and will be significantly enhanced by integration with artificial intelligence-driven analytics. Ultimately, spatially resolved molecular signatures may improve donor assessment, enable early risk stratification, and guide precision interventions, advancing a biology-informed approach to liver transplantation.

The choice between total intravenous anesthesia (TIVA) and volatile anesthesia for living donor hepatectomy remains controversial, with limited evidence comparing their impact on donor and recipient outcomes. This study evaluates the association between anesthetic technique and early postoperative outcomes using global prospective data. 1,466 donor-recipient pairs (September 2023-February 2025) from the International LDLT Registry (LDLTregistry.org) were analyzed. Donors were stratified by anesthetic technique (TIVA vs. volatile). Primary outcome was donor morbidity assessed by the Comprehensive Complication Index® (CCI®). Secondary outcomes included complication incidence (grouped by Clavien-Dindo grade), intraoperative blood loss, transfusion requirements, and biochemical markers. Multivariable regression analysis was adjusted for Human Development Index, surgical approach, and graft type. A linear mixed-effects model with a random intercept for transplant center, to account for outcome differences related to individual transplant center practices, was used to evaluate the association between anesthetic technique and donor CCI. TIVA was used for most donor hepatectomies (82.8%) but there was significant regional variation in its use (p<0.001). All seven centers contributing more than 50 cases (50.3% of the total cohort) used TIVA exclusively or predominantly. Use of volatile anesthesia was independently associated with higher donor CCI® scores (regression coefficient 1.69, 95% CI 0.29-3.09, p=0.018), more major complications (6.3% vs. 1.2%, p<0.001), and greater median blood loss (250 mL vs. 100 mL, p<0.001). TIVA was associated with lower transfusion rates (6.0% vs. 11.6%, p=0.002) and fewer biliary complications (2.5% vs. 8.3%, p<0.001). Recipient outcomes, including graft function and biochemical recovery, were comparable between groups. Our findings suggest an association between TIVA use and improved outcomes in living liver donors, with reduced morbidity in multivariable analysis accounting for transplant center and socioeconomic status of the countries where data originated. Further evaluation of this association with large scale international multicenter randomized trials is warranted.

Current liver transplantation (LT) guidelines recognize perceived health-related quality of life as an important outcome of long-term care, yet it remains unclear whether post-transplantation health literacy plays a role in patient-reported physical and mental health. We conducted a large-scale cross-sectional analysis using data from the U.S. All of Us Research Program of adults with documented LT before completing the "Overall Health" survey (n=1,042). Health literacy was assessed with the 3-item Brief Health Literacy Screen (BHLS; range, 3-15), and physical and mental health with PROMIS Global Health T-scores. Multivariable linear regression adjusted for age, sex at birth, race and ethnicity, and education. Associations were compared with those in adults with cirrhosis without LT (n=5,290) and the general All of Us comparator population. Among 747,029 participants, 1,042 LT recipients had evaluable BHLS scores. Marginal health literacy (BHLS ≤12) was present in 372 recipients (35.7%), including 131 (12.6%) with low health literacy (BHLS ≤9). LT patients displayed a lower health literacy compared to the general population (mean BHLS 12.8 vs. 13.4), but higher than adults with cirrhosis (12.4; all p<0.001). Each 3-point BHLS score increase associated with 3.22-point higher Physical Health (95% CI, 2.52-3.92) and 2.85-point higher Mental Health T-scores (95% CI, 2.09-3.60) after adjustment (both p<0.001). The strength of the association did not differ significantly between recipients and either comparator group. Transplant recipients displayed reduced health literacy, and post-transplant health literacy was strongly associated with better patient-reported physical and mental health. These findings identify health literacy as a modifiable dimension of long-term transplant survivorship and support its assessment in post-transplant care.