Atezolizumab-bevacizumab and durvalumab-tremelimumab have established immunotherapy as a first-line standard of care in advanced hepatocellular carcinoma (HCC). Yet, objective response rates (ORRs) remain confined to approximately 15-20%, and no validated predictive biomarker exists for patient selection. Unlike melanoma and lung cancer, conventional markers, including programmed death-ligand 1, microsatellite instability-high status, and tumor mutational burden, have not demonstrated reliable predictive value in HCC. Prior narrative reviews comprehensively catalogued the biomarker landscape through 2022 but predate a wave of clinically significant publications. This narrative review synthesizes evidence published between 2020 and 2026, with particular emphasis on 2023–2026 data, within a unified clinical framework not provided by prior reviews. We critically evaluate tissue-based biomarkers, including the AI-derived Atezolizumab-Bevacizumab Response Signature-Pathology model, spatial multiplex immunohistochemistry, and β-catenin mutational profiling; blood-based biomarkers encompassing circulating tumor DNA for minimal residual disease detection and peripheral immune phenotyping; and serum indices including the CRAFITY score and neutrophil-to-lymphocyte ratio. Hepatitis B virus etiology and non-alcoholic steatohepatitis are discussed as biological modifiers of biomarker performance. We propose an original biomarker-guided clinical algorithm, a comparative clinical readiness table, and a disease-continuum biomarker timeline as practical tools for clinicians and trialists. Prospective biomarker-enrichment trials represent the most critical next step toward clinical translation.

In this study we evaluated the effectiveness of vedolizumab (anti-integrin) vs ustekinumab/risankizumab (anti-interleukin) therapy for isolated small-bowel Crohn's disease using a real-world, multicenter national database. We found that anti-interleukin therapy was more effective for inducing steroid-free remission and reducing hospitalizations.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease characterized by inflammation in the esophagus, occurring in genetically predisposed individuals as a consequence of food antigen sensitization. EoE prevalence has increased exponentially in the last three decades to 40 per 100000 people worldwide, making it a common cause of dysphagia and food impaction in both children and adults. Diagnosis is made by esophageal biopsy showing eosinophilia (≥ 15 eosinophils per high-power field on biopsy). In children the presentation may be feeding intolerance, in adults a form of chronic solid food dysphagia. In EoE, in the absence of treatment, active inflammation inevitably progresses to fibrostenotic remodeling, highlighting the importance of early recognition and therapy. This review outlines the clinical criteria and pathophysiological mechanisms of EoE, biomarkers for the diagnosis of EoE, and the therapeutic strategies for EoE. EoE is characterized by epithelial barrier dysfunction, Th2 inflammation and eosinophil recruitment, with microbiome influences. Diagnosis is made by standard endoscopic biopsy, or by non-intrusive esophageal string test, Cytosponge, or by impedance planimetry. Treatment includes proton pump inhibitors, topical corticosteroids, dietary elimination therapy, endoscopic dilation, and the Food and Drug Administration approved biologic dupilumab. Emerging therapies such as precision medicine and artificial intelligence are also identified as areas for attention.

BACKGROUND:Inflammatory bowel disease (IBD) and myeloproliferative neoplasms (MPNs) share chronic inflammation and immune dysregulation. AIM:We evaluated the incidence of MPNs among patients with IBD and clinical outcomes of IBD-MPN coexistence. METHODS:Two retrospective cohort analyses were conducted using the TriNetX database. First, adults with ulcerative colitis (UC) or Crohn's disease (CD) were compared with matched non-IBD controls to estimate incident MPN risk. A coexistence second analysis included patients with UC or CD who developed MPNs and then were matched to IBD without MPN controls to assess 5-year outcomes, including IBD-related complications, surgical interventions, colorectal cancer (CRC) and primary sclerosing cholangitis (PSC). Medication subgroup analyses were performed to evaluate associations with MPN risk. RESULTS:After matching, 3873 patients with UC-MPN and 3474 patients with CD-MPN were included. Compared with matched non-IBD controls, incident MPN risk was higher in UC (HR 1.60, p = 0.01) and CD (HR 1.56, p < 0.001). In CD, MPN coexistence was associated with higher risks of CRC (HR 1.52, p = 0.012), intestinal fistula (HR 2.84, p < 0.001), obstruction (HR 2.05, p < 0.001), perforation (HR 2.37, p < 0.001), small bowel resection (HR 3.69, p < 0.001) and colectomy (HR 2.10, p < 0.001). In UC, MPN coexistence was associated with higher risks of CRC (HR 1.50, p = 0.001), PSC (HR 1.75, p = 0.03) and pouchitis (HR 1.68, p = 0.003). Exposure to thiopurines (HR 1.28, p < 0.001) was associated with increased MPN risk, whereas TNF, IL-23 and JAK inhibitors were not. CONCLUSIONS:IBD is associated with increased MPN risk, and IBD-MPNs coexistence is associated with worse IBD-related complications and malignancy risk.

Both GLP-1 receptor agonists and bariatric surgery are increasingly used for obesity management in patients with chronic liver disease (CLD). Their comparative long-term hepatic outcomes remain unclear. We aimed to evaluate the risks of primary liver cancer, hepatic decompensation, and all-cause mortality between GLP-1–treated patients and those with prior bariatric surgery. Using the TriNetX U.S. Collaborative Network, we identified adults above the age of 18 with obesity and underlying cirrhosis who either received GLP-1 analogues or had a history of bariatric surgery. The index event was defined as the first instance of having cirrhosis, obesity, and getting either bariatric surgery or GLP-1. Outcomes were assessed ≥ 30 days after index. Propensity score matching (PSM) (1:1) across 22 demographic, clinical, medication, and laboratory variables was done. Kaplan–Meier survival analyses were performed for primary liver cancer, hepatic decompensation, and mortality, with hazard ratios (aHRs) and 95

BACKGROUND:Gastrointestinal (GI) endoscopy is a high-throughput, resource-intensive specialty with a substantial environmental impact. As healthcare systems move toward sustainability, the concept of "green endoscopy" (GE) has gained traction. However, the perceptions and engagement of the endoscopy workforce remain underexplored. OBJECTIVE:This systematic review aimed to evaluate awareness, attitudes, and perceived barriers among healthcare professionals regarding sustainability in endoscopy and to synthesize existing knowledge on workforce engagement with GE practices. METHODS:A systematic search of PubMed, Embase, and the Cochrane Library was conducted up to April 1, 2025, supplemented by gray literature. Included studies reported original data on healthcare professionals' knowledge, attitudes, or practices related to sustainable endoscopy. Due to heterogeneity, a synthesis without meta-analysis (SWiM) approach was used. RESULTS:Five cross-sectional studies involving 1684 participants across various regions were included. Awareness of GE ranged from 16.3% to 67%. While most respondents acknowledged the environmental burden of endoscopy, fewer reported institutional guidelines or training. Key barriers included lack of knowledge (35%), absence of institutional policy (32%), infection control concerns (41%), and financial constraints (26%). Few departments conducted audits or offered sustainability education. A generational divide was noted, with senior staff expressing greater environmental concern. CONCLUSION:Although global interest in sustainable endoscopy is rising, a significant gap exists between awareness and practice. Structured education, clear institutional policies, and support from professional bodies are essential to embed sustainability within endoscopy services.

Despite advances in endoscopic techniques, many colorectal surgeries in the United States are still performed for non-malignant colorectal polyps (NMCRPs). This study evaluated trends, demographic variations, and outcomes of surgeries for NMCRPs among all colorectal surgeries over the past decade. Using the TriNetX nationwide database, we identified adults (≥ 18 years of age) who underwent colectomy or proctectomy for NMCRPs or colorectal cancer between 2013 and 2023. We evaluated the proportion of surgeries performed for NMCRPs, stratified by demographic factors, and compared postoperative adverse events (AEs) between NMCRP and colorectal cancer surgeries. Among 136,721 surgeries, 52,480 (38.4%) were for NMCRPs. The proportion of NMCRP surgeries decreased from 59% in 2013 to 33% in 2023, with the most significant decline between 2013 and 2016. Black individuals showed the highest decrease. Compared with colorectal cancer surgeries, NMCRP surgeries were associated with significantly lower risks of wound, infectious, urinary, pulmonary, gastrointestinal, and cardiac AEs. Although the proportion of NMCRP surgeries has declined, ongoing efforts in education and training are needed to further reduce unnecessary surgeries and improve patient outcomes.

Background:Cholecystectomy (CCY) may alter bile acid flow and gut microbiota, increasing the risk of gastrointestinal disease. Prior studies have suggested that CCY may be associated with bile acid diarrhea and microscopic colitis; however, the association with the new diagnosis of inflammatory bowel disease (IBD) remains unstudied. In this study, we evaluated whether CCY was associated with a greater risk of de novo IBD. Methods:We conducted a retrospective cohort study, analyzing data from the TriNetX network (2010-2024), using 1:1 propensity score matching between adult patients undergoing CCY and controls, based on variables that included demographics, comorbidities and medication use. The primary outcome was risk of de novo IBD. Secondary outcomes included the risk of developing ulcerative colitis (UC) or Crohn's disease (CD). Kaplan-Meier analysis with hazard ratios (HRs) and 95% confidence intervals (CIs) was used to compare time-to-event rates. Results:Among 570,317 matched pairs, CCY was associated with a greater risk of IBD (adjusted HR [aHR] 1.29, 95%CI 1.22-1.35; P<0.001), and specifically CD (aHR 1.83, 95%CI 1.69-1.99; P<0.001), but not the risk of UC. This elevated risk persisted across both sexes and all age groups. Among patient characteristics, tobacco use was associated with the greatest additional risk of IBD post-CCY (aHR 1.43, 95%CI 1.19-1.76; P<0.001). Conclusions:Prior CCY is associated with a greater risk of CD but not UC. These findings support the need for a low threshold to think about CD in patients with gastrointestinal symptoms after CCY.

BACKGROUND:Digestive diseases are a major cause of morbidity and mortality in the United States, placing a substantial burden on healthcare. METHODS:Data from the 2021 Global Burden of Disease study were analyzed for all 50 US states and the District of Columbia. Temporal trends were quantified using estimated annual percentage changes, and correlations with the Socio-Demographic Index were assessed using Pearson's correlation. RESULTS:From 1990 to 2021, total incident digestive diseases cases rose from 20.1 to 26.2 million, a 30.5% increase, while age-standardized incidence rates declined by 9.8%. Age-standardized disability-adjusted life year (DALY) rates decreased by 7.7%, and death rates fell by 5.9%. Most digestive diseases showed declining DALY rates; however, cirrhosis and other chronic liver diseases increased by 4.5% and remained the highest contributor to DALYs, with a 9% rise in mortality. Inflammatory bowel disease also increased, with DALYs rising by 12% in males and 23% in females; mortality rose by 64% in females versus 44% in males. CONCLUSION:These findings reveal both progress and persistent disparities, with higher burdens among women and states with a lower Socio-Demographic Index. Targeted interventions and resource allocation are warranted to address these inequities.

Patients with active inflammatory bowel disease (IBD) often require immunosuppressive therapy to achieve and maintain remission; however, the impact of these medications on influenza risk and the severity of influenza-related complications remains inadequately characterized. Using the TriNetX U.S. Analytics Network, adults (≥ 18 years) with Crohn’s disease or ulcerative colitis during the 2022–2023 influenza season were identified. Patients were stratified by disease activity into two cohorts: (1) active IBD, defined by elevated inflammatory markers, initiation of corticosteroids or a new biologic or small-molecule agent, or documented IBD-related symptoms or complications within the prior six months; and (2) inactive IBD, defined by the absence of these features and no recent immunosuppressive therapy. Propensity score matching (1:1) was used to balance baseline characteristics, and Cox proportional hazards models were applied to estimate hazard ratios for influenza-related outcomes. After propensity score matching, each group had 22,784 patients. The incidence of influenza diagnosis was significantly higher in the active IBD group (HR 1.41; 95