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Abstract Aims Obesity, particularly visceral adiposity, is a key driver of cardiovascular mortality (CVM), yet conventional measures such as body mass index (BMI) inadequately capture fat distribution. The Body Roundness Index (BRI) is a novel anthropometric measure integrating waist circumference and height to better reflect body shape and visceral fat. This study examined the association between BRI and CVM in U.S. adults and across sociodemographic subgroups. Methods and results We analysed data from 31 351 adults (median age 43 yrs, 50% females) aged ≥20 years in NHANES 1999–2018, excluding those with prior cardiovascular disease or cancer. BRI was computed using a validated equation and categorized into quintiles (Q3 as reference). The primary outcome was CVM; secondary outcomes included all-cause, heart disease, and cerebrovascular mortality. Weighted Cox proportional hazards and restricted cubic spline (RCS) models evaluated associations after adjustment for demographic, behavioural, and clinical factors. Subgroup and sensitivity analyses tested consistency and effect modification. During a median follow-up of 10.1 years (IQR: 5.3–14.9 years), 883 cardiovascular deaths occurred. In fully adjusted models, participants in the highest BRI quintile had a 54% higher risk of CVM (HR, 1.54; 95% CI, 1.13–2.08; P = 0.006) vs. Q3. This risk remained high even among those with normal BMI. RCS analysis indicated a modest U-shaped association. Stronger effects were observed among middle-aged adults (45–64 years) and those with higher educational attainment. Conclusion Higher BRI is independently associated with increased cardiovascular mortality, particularly among middle aged adults and those with normal BMI, underscoring its potential as a practical, noninvasive tool for cardiovascular risk stratification. Incorporating BRI into clinical and public health assessment may improve identification of individuals at elevated risk.

Early allograft failure (EAF) after living donor liver transplantation (LDLT) remains a clinical challenge. Existing prediction models developed for deceased donor transplantation poorly apply to LDLT due to distinct surgical and physiological factors. This study identifies clinical determinants of EAF and develops an LDLT-specific prediction model. We conducted a multicenter retrospective cohort study from 17 high-volume LDLT centers (January 2016–December 2020) with external validation at a tertiary center in Saudi Arabia (January 2015–December 2022). The primary outcome was EAF (graft loss or patient death ≤90 d). Multivariable mixed-effects logistic regression identified preoperative/intraoperative risk factors. The EAGLE-LDLT model was constructed using postoperative laboratory values. Performance was compared against established models (EAD, MEAF, A2ALL) using ROC analysis and decision curve analysis. The development cohort included 2944 adult LDLT recipients (67.7% male; median age 55 y; median MELD 14) with a 5.5% EAF rate. External validation included 1020 recipients (median MELD 21, 6.7% EAF). Independent risk factors for EAF were MELD (OR 1.06, 95% CI 1.04–1.08), donor BMI (OR 1.05, 95% CI 1.00–1.10), portal vein thrombosis (OR 1.73, 95% CI 1.13–2.63), and hepaticojejunostomy (OR 1.58, 95% CI 1.06–2.36). The EAGLE-LDLT model incorporating peak ALT (>468 U/L), peak INR (>1.9), and bilirubin (>3.5 mg/dL) and INR (>1.3) at POD7, demonstrated superior discrimination (AUC=0.81) compared with MEAF (AUC=0.77, p =0.004), EAD (AUC=0.67, p <0.001), and A2ALL (AUC=0.65, p <0.001). EAGLE-LDLT achieved balanced sensitivity (75.0%) and specificity (73.7%), effectively stratifying patients into high-risk (15% of patients; 40.4% EAF incidence) and low-risk groups. Preoperative and intraoperative clinical factors predict EAF in LDLT. The EAGLE-LDLT model accurately identifies LDLT recipients at the highest risk for EAF postoperatively.

Abstract Background We aimed to describe the real-world durability of clinical and endoscopic outcomes of upadacitinib (UPA) in ulcerative colitis (UC). Methods We retrospectively analyzed an ongoing multi-center cohort of UC patients(pts) in the United States who were started on UPA for active disease. Primary outcome was clinical remission at 1yr assessed by partial Mayo score(pMS)(resolution of all UC related symptoms and physician global assessment). Secondary outcomes assessed at various timepoints, including after re-escalation, included clinical response(&gt;50%reduction in symptoms utilizing the pMS), endoscopic response (Mayo endoscopic score≤1or absence of erosions/ulcerations) and histological remission(defined as normal or chronic inactive). Durable secondary outcomes achieved at both 6months and at 1yr and beyond were also assessed. Descriptive statistics were performed. Adverse events(AEs) investigated included cardiovascular events and herpes zoster (HZ). Results 416pts were included(Table 1) with median values for age at initiation of36.00yrs(range27-48), disease duration7.00yrs(range3-14)and follow-up 993days(IQR,672-1103), with206(49.52%)with follow-up at 1yr or beyond. Of these, 66.1%had extensive colitis. Induction duration was8wks in 86.5%and16wks in 4.8 %(20/416). Most received an induction dose of45mg(97.1%)and maintenance dose of30mg(85.8%). Among the evaluable population at1yr and beyond, 62.5%(45/80)were in clinical remission, 75.9%(22/29)in endoscopic response with58.6%(17/29) in remission and66.6%(20/30)in histological remission. At 6months, clinical remission was51.6%(42/93), endoscopic response was 75%(24/32) of which43.75%(14/32)were in remission and histologic remission was seen in 40.8%(20/49).Durable secondary outcomes of clinical remission were seen in 71.4%(30/42), endoscopic improvement in 45.8%(11/24), and histologic remission in35%(7/20). Re-escalation to 45mg occurred in 35pts, of which48.6%(17/35)were re-escalated due to incomplete induction clinical response with all achieving response(11 in remission). The rest(18/35)were re-escalated for clinical relapse after initial remission where72.2%(13/18)were able to recapture remission. After re-escalation,54.3%(19/35)continued on 45mg daily. AEs were reported in12.7%with HZ in 7pts(2.1%). One pt aged53yrs had an episode of TIA after 1yr on UPA at 15mg, without pre-existing cardiovascular risk factors and UPA use is ongoing at the same dose. There were no reported episodes of worsening of pre-existing cardiovascular disease or DVT/PE. Conclusion UPA is durably effective and safe in a real-world clinical setting with re-escalation to 45mg capturing response in a majority of the pts. Ongoing recruitment will provide further evidence on long term effectiveness and safety. Conflict of interest: Ms. Huang, Katherine: No conflict of interest Chandnani, Arun: No conflict of interest Samaan, Sami: None Tan, Tingyi: I have no conflict of interests to declare. Ramesh, Prajith Raj: None Conlon, Caroline: No conflict of interest Klein, Jeremy: None Reddy, Nikhil: No conflict of interest Ayoub, Malek: None Cervantes Limon, Gabriela: none Myers, Melissa: None Bucaram, Martha: No conflict of interest Lieto, Stephen: No conflict of interest Scalzo, Nicholas: No conflict of interest Cohen, Benjamin: Abbvie - consulting and speaking ALPCO - consulting J & J Innovative Medicine - consulting Takeda - consulting and speaking Emmes Biopharma Services LLC - DSMB Pfizer - consulting Mohamed, Islam: nothing to declare Ciorba, Matthew: Advisory Board: Janssen, AbbVie, Pfizer, Geneoscopy Consulting: Janssen, AbbVie, Pfizer, Geneoscopy Grant contracts: Janssen, Pfizer, Incyte Shukla, Richa: Speakers bureau - Abbvie and Lilly Wright, Michael: None Xu, An Tao: No conflict of interest Chowla, Navreet: No conflict of interest Ogholikhan, Sina: Abbvie Medical Director Kujawski, Michelle: Abbvie Scientific Director Dulaney, David: Speaker bureau - Regeneron Speaker bureau - Sanofi Speaker bureau - Takeda Speaker bureau - Eli Lilly Fenster, Marc: none Benson, Caroline: No conflict of interest Alhobayb, Tamara: No conflict of interest Berinstein, Jeffrey: No conflict of interest Shivashankar, Raina: Abbvie and BMS - speaker bureau Janssen and Celltrion - grant for IBD fellowship funding Pfizer - consultant Bishu, Shrinivas: None Patel, Anish: speaker: abbvie, J & J, Lilly, BMS, Pfizer, Phathom, Takeda consultant: abbvie Ungaro, Ryan: Personal Fees: AbbVie, Bristol Myers Squibb, Genentech, Lilly, Pfizer, Janssen, Takeda Johnson, Amanda: Research grant: Abbvie, Spyre Therapeutics Pekow, Joel R.: CVS Health - Consulting Abbvie, Eli Lilly, Pfizer, Johnson and Johnson - Stocks Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. Deepak, Parakkal: Parakkal Deepak has received research support under a sponsored research agreement unrelated to the data in the abstract from AbbVie, Johnson and Johnson, Sanofi, Merck, Teva, Direct Biologics, Tr1x, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Eli Lilly, AstraZeneca, Spyre and Agomab, has received consulting fees from Johnson and Johnson, Abbvie, Merck, Sobi, Celltrion, Fresenius Kabi, Asahi Kasei Pharma, Sandoz and CorEvitas, LLC and has served on the board of the Srategic Alliance for Intercultural Advocacy in GI.

Abstract Background A subset of risankizumab (RZB)-treated patients experience suboptimal or secondary loss of response to standard dosing. We explored factors associated with future RZB dose-optimization, and outcomes of optimization in a multicenter consortium of adults with Crohn’s Disease (CD). Methods Baseline characteristics at time of RZB initiation and subsequent clinical, endoscopic, and biochemical outcomes were collected in a multi-center cohort. Outcomes for dose-optimized RZB were reported as clinical response and remission (based on HBI or PGA when HBI unavailable), endoscopic remission (based on SEMA-CD or absence of ulcers when SEMA-CD not available), and biochemical response. Characteristics were compared between standard and dose-optimized groups using chi-square and two-sample t-tests. Additional models adjusting for age and sex assessed predictors of dose optimization. Results We identified 309 patients treated with standard dose and 58 for whom dose-optimized RZB was recommended. Of the 58, 29 were excluded from outcomes analysis due to lack of follow-up (n = 19) or insurance denial of dose optimization (n = 10). Demographic information is outlined in Table 1. Baseline characteristics associated with future dose optimization included number of prior advanced therapies (ATs) (OR, 1.29, p &lt; 0.001), prior anti-TNF (OR,4.06; p = 0.022), and prior ustekinumab (UST) use (OR,1.82; p = 0.053) (Table 2). The 29 patients included in the outcome analysis received dose-optimized RZB for primary non-response (n = 2), partial response (n = 23), or secondary loss of response (n = 4) after a median of 321 days (IQR, 234-440) from index RZB start. Median follow-up after dose optimization was 217 days (IQR, 147-331). All patients were AT-exposed (Table 1). Baseline clinical symptoms were present in 27 patients (93.1%), with median HBI of 6.5 (IQR, 6.0-8.0). Active endoscopic disease was observed in 11/12 patients (91.7%) who had baseline endoscopy. Dosing was every 4 weeks in 19 (65.5%), every 6 weeks in 9 (31.0%), and combined IV re-induction plus every 4-weeks in 1 (3.4%) patient. Clinical response and remission was seen in 16 (55.2%) and 12 (41.4%) patients, respectively. A ≥ 50% CRP reduction was seen in 5/12 (41.7%) patients with baseline elevated CRP. Among 7 patients with baseline active endoscopic disease with available follow-up, 3 (42.9%) achieved endoscopic remission. No adverse events were reported. Conclusion In this multi-center retrospective cohort, prior AT-exposure (especially anti-TNF) was associated with need for RZB dose-optimization. Dose optimization successfully captured clinical response in a significant proportion of patients who experienced partial response or loss of response to RZB. Conflict of interest: Johnson, Amanda: Research grant: Abbvie, Spyre Therapeutics Ramesh, Prajith Raj: None Said, Hyder: No conflict of interest Huang, Katherine: No conflict of interest Devi, Jalpa: none Pekow, Joel R.: CVS Health - Consulting Abbvie, Eli Lilly, Pfizer, Johnson and Johnson - Stocks Alhobayb, Tamara: No conflict of interest Bassmeyer, Blake: No conflict of interest Mohamed, Mouhand: No conflict of interest Shivashankar, Raina: Abbvie and BMS - speaker bureau Janssen and Celltrion - grant for IBD fellowship funding Pfizer - consultant Rathi, Jaya: No conflict of interest Luu, Bryan: No conflict of interest Khan, Abdul: No conflict of interest Loftus, Jr, Edward: Grant: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, UCB. Personal Fees: AbbVie, Allergan, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Iterative Scopes, Janssen, Ono Pharma, Pfizer, Sun Pharma, Takeda, UCB. Bishu, Shrinivas: None Patel, Anish: speaker: abbvie, J & J, Lilly, BMS, Pfizer, Phathom, Takeda consultant: abbvie Shukla, Richa: Speakers bureau - Abbvie and Lilly Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. Ungaro, Ryan: Personal Fees: AbbVie, Bristol Myers Squibb, Genentech, Lilly, Pfizer, Janssen, Takeda Deepak, Parakkal: Parakkal Deepak has received research support under a sponsored research agreement unrelated to the data in the abstract from AbbVie, Johnson and Johnson, Sanofi, Merck, Teva, Direct Biologics, Tr1x, Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals, Roche Genentech, Eli Lilly, AstraZeneca, Spyre and Agomab, has received consulting fees from Johnson and Johnson, Abbvie, Merck, Sobi, Celltrion, Fresenius Kabi, Asahi Kasei Pharma, Sandoz and CorEvitas, LLC and has served on the board of the Srategic Alliance for Intercultural Advocacy in GI.

Background: Transradial artery access (TRA) is the favored approach for percutaneous coronary intervention (PCI) and coronary angiography (CAG). However, transulnar artery access (TUA) has emerged as an alternative, particularly when TRA is not feasible. This systematic review and meta-analysis aims to compare the efficacy and safety of TUA versus TRA in patients undergoing PCI and CAG. Methods: From inception to August 2025, a systematic search of electronic databases was conducted. Data were synthesized using a random-effects model, and heterogeneity was assessed using the I 2 statistic. Results: Nine RCTs involving 6089 patients were included. Meta-analysis revealed no significant difference in procedural success between TUA and TRA (RR: 0.93, 95% CI: 0.82–1.06, P = 0.28, I 2 = 99%). Similarly, puncture success rates were comparable (RR: 0.95, 95% CI: 0.91–1.00, P = 0.06, I 2 = 83%). Secondary outcomes showed no significant differences in puncture attempts or hematoma incidence, but TRA was associated with a shorter procedure time (MD: 0.89, 95% CI: 0.27–1.50, P = 0.005). Conclusion: TUA provides a viable alternative to TRA, with similar success rates and complication profiles. However, TRA remains superior in terms of procedure time. Further large-scale RCTs are warranted to confirm these findings and refine clinical guidelines.

733 Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have advanced the treatment of type 2 diabetes mellitus (T2DM) yet their association with cancer risk remains subject of ongoing research. While case reports and pharmacovigilance data have linked GLP-1RA’s to pancreatitis, large randomized trials and observational studies have not consistently shown an increased risk of pancreatic cancer. Chronic pancreatitis (CP) is a well-established risk factor for pancreatic cancer, yet the impact of GLP-1 RA therapy in this high-risk population is unknown. In this study, we aim to evaluate the association between GLP-1 RA use and pancreatic cancer incidence among patients with CP, and among those with CP and T2DM. Methods: We performed a retrospective cohort study using ICD-10 codes within TriNetX, a healthcare database of over 150 million patients in the United States. In the first analysis, adult patients with pre-existing CP were identified, and the 5-year incidence of pancreatic cancer between GLP-1 RA (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, and lixisenatide) users and non-users was compared from 2015-2025. In the subsequent analysis, we restricted the cohort to adults with CP and T2DM and repeated the comparison. Patients with prior diagnosis of pancreatic cancer were excluded from both analyses. All cohorts were propensity score matched (PSM) on age, sex, race, tobacco use, alcohol use, hypertension, hyperlipidemia, obesity, and pancreatic cysts. Results: We identified 95,391 with CP, including 3,139 GLP-1 RA users and 92,252 non-users. After PSM, GLP-1 RA use was associated with a lower incidence of pancreatic cancer (0.6% vs. 1.5%, OR 0.39 [0.22, 0.67]). Similarly, amongst patients with CP and T2DM, GLP-1 RA use was associated with a lower incidence of pancreatic cancer (0.7% vs. 1.6%, OR 0.44 [0.25, 0.75]). Conclusions: GLP-1 RA use was associated with a significantly reduced incidence of pancreatic cancer in all patients with CP and in those with CP and T2DM. Given the elevated cancer risk in CP, these findings suggest a potential protective effect of GLP-1RA use in this high risk population. Prospective studies will be important to further analyze and confirm this potential benefit.

632 Background: Paltusotine is an oral, nonpeptide, selective somatostatin receptor 2 agonist. In a phase 2 study, treatment with once-daily paltusotine reduced the frequency and severity of carcinoid syndrome (CS) symptoms and was well tolerated. The effect of paltusotine on biomarkers of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) was further explored. Methods: This exploratory study, without formal power calculations, included an 8-week randomized treatment phase (completed) and a 102-week open-label extension phase (currently ongoing). The purpose was to evaluate safety, pharmacokinetics, and exploratory efficacy endpoints, including changes in biomarkers of paltusotine treatment. Enrolled patients were adults with a stable, documented grade 1 or 2 neuroendocrine tumor (NET) and CS. These patients were actively symptomatic and either untreated with somatostatin receptor ligand (SRL) therapy (average of ≥4 bowel movements [BMs] per day or >2 flushing episodes per day in ≥2 days over a 2-week period) or washed out of SRL therapy (symptoms previously controlled on SRL), with demonstrated symptom worsening after washout. Patients were randomized to once-daily paltusotine 40 mg or 80 mg; one optional uptitration (from 40 mg to 80 mg or 80 mg to 120 mg) was permitted. Blood samples for assessment of biomarkers (serum serotonin and plasma 5-HIAA) were collected longitudinally from screening to end of treatment. Upper limit of normal was prespecified as 541 ng/mL for serotonin and 22 ng/mL for 5-HIAA. This analysis focuses on changes in biomarker from baseline to the end of 8-week randomized treatment phase and after approximately one year (48 weeks). Results: Thirty-six patients (n=9 untreated; n=27 SRL washout) were randomized. Mean age was 60.8 years (range 35-83), and 52.8% were female. Nineteen patients had grade 1 NETs, and 17 had grade 2 NETs. As reported previously, treatment with once-daily, oral paltusotine was well tolerated and reduced the frequency and severity of CS symptoms, justifying further clinical development of the 80 mg dose. Mean serum serotonin decreased from 1553.0 ng/mL at baseline to 643.9 ng/mL at Week 8, and mean plasma 5-HIAA decreased from 245.1 ng/mL to 159.7 ng/mL. There was a trend of untreated patients achieving a greater reduction in comparison to washout patients. At 48-week follow-up, mean serum serotonin was stabilized at 791.50 ng/mL (n=20), and mean plasma 5-HIAA was stabilized at 190.45 ng/mL (n=20). Conclusions: Paltusotine significantly reduced serotonin and 5-HIAA levels, with effects maintained at 48 weeks. Biomarker reductions paralleled reductions in BM and flushing frequency. These findings support further investigation in the ongoing phase 3 study (CAREFNDR, NCT07087054). Clinical trial information: NCT05361668 .

605 Background: Multiple treatment modalities are available for localized hepatocellular carcinoma (HCC), and current Barcelona Clinic Liver Cancer (BCLC) guidelines recommend ablation for patients with a limited number of small tumors, not amenable to resection or transplantation. However, in recent years, stereotactic body radiation therapy (SBRT) has been increasingly used for localized disease. Patient outcomes based on treatment modality are not well understood. Methods: We conducted a retrospective analysis using the National Cancer Database (NCDB) to identify patients with a history of stage I/II HCC with tumors ≤ 5 cm who had received local therapy with either radiofrequency ablation (RFA) or SBRT between 2006 and 2021. A propensity score matched analysis was conducted accounting for patient demographics, facility region and tumor level characteristics, as well as an inverse probability of treatment weight-adjusted (IPTW) analysis. Overall survival was estimated using the Kaplan-Meier method. Results: We identified 14,516 patients meeting inclusion criteria, including 13,036 who received RFA and 1,480 who received SBRT. Demographic factors associated with receipt of SBRT included age >50 years, female sex, and treatment in the Middle Atlantic and East North Central regions, as well as clinical factors including larger tumor size (>3 to 5 cm), severe fibrosis/cirrhosis, and stage II disease ( p <0.05 for all). Factors associated with receipt of RFA include black race, higher Charlson-Deyo Comorbidity Scores, treatment at a comprehensive cancer program or integrated network cancer program, and treatment in the East South Central, West North Central, West South Central, Mountain, and Pacific Regions ( p <0.05 for all). Median time from diagnosis to treatment initiation was longer for those who received SBRT (66.3 vs 84.6 days, p <0.001). In a propensity matched analysis, mOS was 45.1 months for those receiving RFA vs 30.8 months for those receiving SBRT ( p <0.001). An IPTW analysis showed similar survival benefit with RFA over SBRT (mOS 51.0 vs 30.5 months, p <0.001). This OS benefit was observed in subset of patients with tumors <3cm in size. Conclusions: In this propensity matched analysis controlling for relevant patient and tumor factors, RFA was associated with improved survival. Prospective studies will be important to further analyze differences in patient outcomes.

ABSTRACT Introduction Desmoplastic small round cell tumor (DSRCT) is a rare malignant mesenchymal neoplasm of polyphenotypic differentiation, characterized by EWSR1‐WT1 gene fusion. Despite multimodality therapy, the tumor carries poor prognosis. We report cytomorphological, immunohistochemical (IHC) and molecular features of seven cases of DSRCT from four patients. Materials and Methods A retrospective review of cytology smears, biopsies and molecular features of cases diagnosed as DSRCT at Department of Pathology, Henry Ford Health System, and Indiana University, USA between 2016 and 2022 were performed. A total of seven cases of DSRCT from four patients were included in this study. The cytological findings were correlated with concurrent or subsequent biopsy findings. Results All patients were male, with age ranging from 21 to 29 years. Two patients had primary tumor in the abdomen, one in the retroperitoneum, and one in the inguinal region. The tumors measured from 7.5 to 17 cm in size. Six out of seven cases showed typical hypercellular smears of small round cells with inconspicuous nucleoli, scant cytoplasm, and rare nuclear molding. The cytomorphology in Case no. 1 was unusual, showing discohesive pleomorphic tumor cells with large irregular nuclei, prominent nucleoli, occasional binucleation, and frequent mitotic activity. A subset of tumor cells demonstrated rhabdoid features. The tumor cells were positive for keratins (dot‐like), desmin, WT‐1, and CD15. In Case no. 4, the immunohistochemistry for desmin and WT‐1 was unusually negative reflecting the variability of the staining pattern. Three cases were positive for EWSR1 rearrangement by fluorescence in situ hybridization (FISH) and one positive for EWSR1‐WTI gene fusion by reverse transcriptase‐polymerase chain reaction (RT‐PCR). All seven cases had concurrent/subsequent surgical pathology diagnosis consistent with DSRCT. Conclusion Cytologic diagnosis for DSRCT is challenging but can be achieved with appropriate cytomorphology, IHC profiles, molecular studies, and demographic information. Rare rhabdoid differentiation can occur in DSRCT and can be present in effusion cytology.

Living donor liver transplantation (LDLT) is an established therapy with curative intent for pediatric and adult patients with acute liver failure and end-stage liver disease. Donor safety remains paramount and commences during preoperative evaluation and assessment. Given the importance of the topic, the International Liver Transplantation Society and International Living Donor Liver Transplantation Group consensus conference on Living Liver Donor Safety was convened in March 2025 (Toronto, Canada). Recommendations were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for assessment of recommendations, and the Danish model of consensus was followed. This report presents 28 recommendations from the working group focused on addressing clinically relevant questions related to the preoperative aspects of living donor safety including assessment of donor acceptability (age, body mass index and hepatic steatosis; medical conditions and contraindications), medical and surgical workup (liver function and procoagulant workup; anatomical considerations and safe remnant), and psychosocial evaluation (timing and team; underlying conditions; non-directed, paired, and anonymous directed donors; urgent living donor workups for acute liver failure).