BACKGROUND AND AIM:Significant health disparities persist in alcohol-associated liver disease (ALD), largely driven by social determinants of health (SDOH). However, the influence of neighbourhood-level SDOH on ALD outcomes remains underexplored. In this study, we aimed to evaluate how neighbourhood-level SDOH are associated with disease burden, comorbid conditions, and mortality in individuals with ALD. METHODS:We conducted a retrospective cohort study of patients with ALD in the Banner Health System, representing hospitals across Arizona, California, Nevada, Wyoming and Colorado, from January 2012 to October 2024 using ICD codes. Neighbourhood-level SDOH were quantified using the Social Deprivation Index (SDI). Patients were stratified into quartiles based on SDI score, with Quartile 4 representing the most socioeconomically disadvantaged neighbourhoods. Primary outcomes included incidence of mortality, cirrhosis, major adverse liver outcome (MALO), Type 2 diabetes mellitus, any cancer, and major adverse cardiovascular events (MACE). A multivariable competing risk analysis was performed adjusting for age, sex, race/ethnicity, insurance type, primary language, smoking status, Type 2 diabetes mellitus, hypertension, hyperlipidemia, aspirin use, statin use, alcohol use disorder and a composite mental-health/substance-use disorder variable encompassing depression, anxiety disorders, post-traumatic stress disorder, bipolar disorder, schizophrenia, and non-alcohol substance use disorders. RESULTS:Among 11,394 patients with ALD and available SDI data, 6747 had ≥ 365 days of follow-up. The average age was 51 years and 65.6% were female; 68.8% were non-Hispanic White, 19.7% Hispanic, 5.9% Native American/Alaskan Native (NA), 3.2% Black, and 0.4% Asian/Pacific Islanders. Patients residing in the most disadvantaged neighbourhoods (Quartile 4) were significantly younger, more likely to be female, had a higher median BMI, and more frequently reported a non-English primary language compared with those in the least disadvantaged areas (Quartile 1). Patients in the most deprived neighbourhoods were more likely to be Hispanic, Black, or Native American/Alaska Native and to be uninsured or on Medicaid, whereas those in the least disadvantaged neighbourhoods predominantly had private insurance. Individuals in Quartile 4 had increased mortality (adjusted hazard ratio [aHR]: 1.48, 95% Confidence Interval [CI]: 1.09-2.01) compared with individuals in Quartile 1. CONCLUSIONS:In this large and demographically diverse ALD cohort, residing in socioeconomically disadvantaged neighbourhoods was associated with increased risk of mortality. These findings support the need for contextually tailored clinical interventions and broader treatment strategies that target upstream sociocultural and environmental factors that are associated with health outcomes. Addressing neighbourhood-level SDOH through community engagement, policy reform, and cross-sector partnerships to improve collaborative care efforts is needed to reduce health disparities in ALD.

Background: Alcohol-associated liver disease (ALD) is a leading cause of advanced liver disease and liver transplantation worldwide. Cardiometabolic risk factors (CMRFs) may worsen ALD prognosis. While recent nomenclature acknowledges the impact of CMRFs in steatotic liver disease with low-to-moderate alcohol use, individuals with high alcohol intake are still classified as having ALD regardless of CMRF status. We conducted a systematic review to evaluate the impact of CMRFs, primarily diabetes, obesity, and metabolic syndrome, on clinical outcomes in patients with ALD. Methods: We performed a systematic review of peer-reviewed studies published through October 21, 2025, as well as abstracts from the AASLD, EASL, DDW, ACG, and APASL conferences from 2023 to 2025. We included studies involving adults (≥18 y) with ALD that assessed at least one CMRF (eg, diabetes, obesity, metabolic syndrome) and reported longitudinal clinical outcomes. Primary outcomes included incident cirrhosis, hepatocellular carcinoma (HCC), overall and cause-specific mortality, cardiovascular events, liver-related complications, and liver transplantation. Results: Nineteen studies comprising 132,054 patients with ALD met the inclusion criteria. Diabetes was consistently associated with increased risks of overall mortality [adjusted hazard ratio (aHR) 3.00], liver-related mortality (aHR 3.60), HCC (hazard ratios 1.6–21.7), and cardiovascular mortality (aHR 19.91). Elevated BMI was linked to higher all-cause mortality (aHR 1.16–1.58), cardiovascular mortality (aHR 3.76), HCC incidence (HR 2.0–2.9), and liver-related mortality (aHR 16.22). Metabolic syndrome was associated with increased overall (HR 1.27–2.37) and liver-related mortality (HR 1.47–2.06). A greater burden of CMRFs was correlated with lower transplant-free survival and reduced rates of hepatic recompensation. Conclusion: Diabetes, obesity, and metabolic syndrome are associated with worse hepatic and extrahepatic outcomes in ALD.

Background: Social determinants of health (SDoH), including poverty and social isolation, have emerged as important contributors to adverse outcomes of chronic diseases. However, their impact on patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains poorly characterised. This study aimed to assess the association between social vulnerability in MASLD and liver-related and cardiovascular outcomes. Methods: We conducted a population-based retrospective cohort study using the TriNetX network, which aggregates de-identified electronic health records from healthcare systems across the U.S. Patients with MASLD and at least one International Classification of Diseases, Tenth Revision (ICD-10) code for documented social vulnerability (Z59.5, Z59.6, Z56.0 and Z60.2) were compared to non-socially vulnerable individuals. Outcomes, including major adverse liver outcomes (MALO), major adverse cardiovascular events (MACE), hepatocellular carcinoma (HCC) and other cardiovascular complications, were assessed over a 5-year follow-up using Cox proportional hazards models. Results: Individuals with MASLD and documented social vulnerability were at higher risk of MALO (8.3% vs. 4.4%; HR 1.69, 95% CI: 1.42-2.01). Cardiovascular morbidity was consistently elevated including MACE (22.7% vs. 12.5%; HR 1.64, 95% CI: 1.46-1.83), arrhythmias (34.4% vs. 17.8%; HR 1.81, 95% CI: 1.64-2.00) and heart failure (12.4% vs. 6.7%; HR 1.64, 95% CI: 1.42-1.89). The incidence of HCC did not differ between documented socially vulnerable and non-socially vulnerable individuals with MASLD. Conclusions: Documented social vulnerability is independently associated with higher risks of liver and cardiovascular complications in MASLD. These findings underscore the importance of integrating SDoH into MASLD management and risk prediction models to address disparities in long-term outcomes.

BACKGROUND:Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC). Given the wide variation in AFP values, conventional linear regression methods may provide an incomplete understanding of complex predictor relationships. Therefore, we utilized quantile regression to examine the association of clinical factors with AFP distribution. METHODS:In this multicenter study, we analyzed retrospective data from an adult HCC cohort, collected across nine tertiary healthcare institutions from 2003 to 2021. Quantile regression, which can model covariate effects at different specified points of the outcome distribution, was used to account for heterogeneity across the AFP value range, assessing the effects of predictors associated with AFP levels at the 0.10, 0.50, and 0.90 quantiles. Logistic regression was performed with AFP < 20 ng/mL and ≥ 20 ng/mL groups. RESULTS:The cohort included 2298 individuals with HCC, with median AFP of 13.70 ng/mL. Multivariable quantile regression determined that factors such as Asian ethnicity, elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), Barcelona Clinic Liver Cancer (BCLC) stage, hepatitis B (HBV), and hepatitis C (HCV) were associated with higher AFP, while male sex, older age, higher BMI, and elevated creatinine were associated with lower AFP levels. Compared to metabolic dysfunction-associated steatotic liver disease, HBV (β = 0.44 at Q50) and HCV (β = 0.30 at Q10; β = 0.40 at Q50) were associated with higher AFP. CONCLUSION:There is substantial heterogeneity in how clinical factors influence AFP levels across its distribution. These data may stimulate the development of more granular cut-points for AFP that differ according to disease stage and etiology.

Background:Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits, but there are little data in solid organ transplant populations. We aimed to assess the effect of GLP-1 RA or SGLT2i on the incidence of post-transplant major adverse cardiovascular events (MACE), graft failure, renal outcomes, and mortality in liver or simultaneous liver-kidney transplant populations. Methods:A retrospective chart review of adults with diabetes mellitus and either solitary liver or simultaneous liver-kidney transplantation from January 2012 to March 2022 was completed. The multivariate Cox regression and Fine and Gray competing risk regression analyses were used. Results:Among 457 patients, 33 received a GLP-1 RA or SGLT2i. The GLP-1 RA/SGLT2i group had a lower incidence of graft failure (P = 0.038), new-onset end-stage renal disease requiring dialysis (P = 0.012), and new-onset post-liver transplant MACE at 5 y (adjusted subdistribution hazard ratio, 0.24; P = 0.049; 95% confidence interval, 0.059-0.99). Conclusions:After propensity score matching, the incidence of 5-y post-liver transplant MACE-free survival was significantly higher, and mortality was significantly lower in the GLP-1 RA/SGLT2i group. The use of a GLP-1 RA/SGLT2i post-liver transplant was associated with a lower incidence of new-onset MACE, graft failure, and new-onset end-stage renal disease requiring dialysis. There was an improvement in survival after propensity score matching.

INTRODUCTION:Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) represent a spectrum of liver conditions that can gradually progress to cirrhosis. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have shown benefits in reducing hepatic steatosis and liver-related events in MASLD. This study aims to assess whether SGLT-2 inhibitors are associated with a reduced risk of all-cause mortality and disease-specific outcomes in patients with MASH cirrhosis and type 2 diabetes (T2D). METHODS:A retrospective cohort study was performed using TriNetX. Patients with T2D and MASH cirrhosis on SGLT-2 inhibitors were matched 1:1 with other glucose-lowering drugs (oGLDs) based on demographics, comorbidities and medications. Primary outcomes included all-cause mortality, hepatic decompensation and major adverse liver outcomes (MALO). Cox-proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence interval (CI). RESULTS:A total of 51 427 patients with MASH cirrhosis and T2D were identified, of which 6833 (13.28%) were on SGLT-2 inhibitors. Patients on SGLT-2 inhibitors (n = 6449, mean age 63.7 years, 52.9% female) were matched with 6449 individuals (mean age 63.9 years, 53.5% female) on oGLDs. The SGLT-2 inhibitors cohort had statistically significantly lower risk of all-cause mortality (HR: 0.58, 95% CI: 0.53-0.63), hepatic decompensation (HR: 0.85, 95% CI: 0.81-0.90) and MALO (HR: 0.88, 95% CI: 0.83-0.93). CONCLUSION:SGLT-2 inhibitors are associated with a reduced risk of all-cause mortality in patients with MASH cirrhosis and T2DM, which may be partly attributable to a lower risk of hepatic decompensation and subsequent events. Further studies are warranted as SGLT-2 inhibitors may serve as an adjunctive therapy for patients with MASH cirrhosis.

Gastrointestinal (GI) cancer poses a significant burden in the Asia-Pacific region. Growing and aging populations, cancer prevention efforts, and treatment advances have all influenced GI cancer trends. This review provides an updated overview of GI cancer epidemiology in the region, using age-standardized incidence rates (ASIRs) and death rates (ASDRs) from the Global Burden of Disease 2021 and the Global Cancer Observatory 2022. Differences between the two datasets should be interpreted with consideration of variations in methodology, standard populations, and reporting years. Colorectal cancer ranks highest in all regions across both datasets for ASIR. However, ASDR is less uniform. There is geographic heterogeneity in GI cancer burden, with Mongolia disproportionately impacted by esophageal, gastric, and liver cancers, while Japan and Australia have a considerable burden of colorectal and pancreatic cancers, along with gastric cancer in Japan. Lower mortality-to-incidence ratios for colorectal and gastric cancers may reflect the effective implementation of screening programs, facilitating early detection and effective treatments. Conversely, esophageal, pancreatic, and gallbladder cancers have lower ASIRs but incidence-to-mortality ratio near one, likely reflecting lack of cost-effective screening and poor prognosis with late-stage diagnoses. Several South-East Asian and Pacific Island countries with lower socioeconomic status show markedly lower ASIRs and ASDRs, which may reflect differences in data availability, reporting, and healthcare access, highlighting the need to strengthen national cancer registry systems. Altogether, this review offers up-to-date GI cancer epidemiology insights to support healthcare providers and policymakers in developing targeted strategies to reduce the burden of GI cancer in the Asia-Pacific region.

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

BACKGROUND:Alcohol-associated liver disease (ALD) is a leading cause of liver-related mortality and is increasingly recognized for its contribution to cardiovascular diseases. The renin-angiotensin-aldosterone system (RAAS), including angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), has demonstrated benefits in modulating inflammatory pathways. Clinical data regarding the effects in patients with ALD remain limited. METHODS:We conducted a retrospective cohort study utilizing the TriNetX platform. Patients with ALD who were prescribed ACEI/ARB were compared with those prescribed calcium channel blockers (CCB). Propensity score matching (1:1) was applied to balance baseline characteristics. The primary outcome was all-cause mortality. Secondary outcomes included alcohol-associated hepatitis (AH), major adverse cardiovascular events (MACE), major adverse liver outcomes (MALO), and sepsis. Patients were followed for 5 years. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). RESULTS:After matching, 7884 patients were included (3942 per group). ACEI/ARB use was associated with a significantly lower risk of all-cause mortality (HR: 0.70, 95% CI: 0.64-0.78, p < 0.001) compared with CCB use. Furthermore, the ACEI/ARB cohort demonstrated significant risk reductions across all secondary outcomes, including MACE (HR: 0.69, 95% CI: 0.61-0.77, p < 0.001), MALO (HR: 0.81, 95% CI: 0.73-0.90, p < 0.001), AH (HR: 0.88, 95% CI: 0.80-0.97, p = 0.008), and sepsis (HR: 0.61, 95% CI: 0.53-0.70, p < 0.001). CONCLUSIONS:In this large real-world cohort, ACEI/ARB use in patients with ALD was associated with reduced risks of mortality, cardiovascular events, liver events, AH, and sepsis, supporting a potential protective role of RAAS inhibition in ALD patients.

811 Background: Lean individuals with MASLD may represent a distinct subgroup at increased risk for gastrointestinal cancers, though evidence from real-world data remains limited. This study aimed to investigate the association between lean MASLD and GI cancer incidence using a large, multicenter retrospective cohort. Methods: We performed a population-based retrospective cohort study utilizing the TriNetX network, which compiles de-identified electronic health records from healthcare institutions across the United States. Patients with MASLD were classified as lean or non-lean (BMI ≥ 25) and were compared accordingly. The primary outcomes were gastrointestinal cancers and their subtypes, evaluated over a 5-year follow-up period using Cox proportional hazards models. Results: After 1:1 propensity score matching on demographics, comorbidities, labs, and medication use, 34,663 patients remained in each group with comparable characteristics. Over 5 years, lean individuals with MASLD exhibited significantly higher incidence of overall GI cancer compared to non-lean individuals (2.2% vs. 1.4%; HR 1.66, 95% CI: 1.48–1.87). Elevated risks were observed for esophageal cancer (HR 3.00, 95% CI: 1.80–4.99), gastric cancer (HR 2.96, 95% CI: 2.00–4.37), pancreatic cancer (HR 2.55, 95% CI: 2.00–3.26), colorectal cancer (HR 1.53, 95% CI: 1.13–2.06), biliary tract cancer (HR 1.76, 95% CI: 1.16–2.67), and unspecified GI cancers (HR 2.03, 95% CI: 1.17–3.53). Liver cancer rates were similar between groups (HR 1.05, 95% CI: 0.85–1.31). Conclusions: Lean MASLD was associated with a significantly increased risk of several gastrointestinal cancers, underscoring the need for tailored cancer surveillance strategies in this vulnerable subgroup. 5-year incidence of clinical outcome in lean and non-lean metabolic dysfunction-associated steatotic liver disease. Outcome MASLD leanEvents N (%) MASLD non-leanEvents N (%) Hazard Ratio (95% CI) p-value Gastrointestinal cancer 709 (2.2%) 455 (1.4%) 1.66 (1.48−1.87) <0.001 Subtypes Esophageal cancer 57 (0.2%) 20 (0.1%) 3.00 (1.80−4.99) <0.001 Gastric cancer 96 (0.3%) 34 (0.1%) 2.96 (2.00−4.37) <0.001 Liver cancer 163 (0.5%) 162 (0.5%) 1.05 (0.85−1.31) 0.652 Colorectal cancer 104 (0.3%) 71 (0.2%) 1.53 (1.13−2.06) 0.006 Pancreatic cancer 223 (0.7%) 92 (0.3%) 2.55 (2.00−3.26) <0.001 Biliary tract cancer 59 (0.2%) 35 (0.1%) 1.76 (1.16−2.67) 0.007 Unspecified site gastrointestinal cancer 37 (0.1%) 19 (0.1%) 2.03 (1.17−3.53) 0.010 CI: confidence interval; HR: hazard ratio.