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Background: The global burden of metabolic diseases is increasing, but estimates of their impact on primary liver cancer are uncertain. We aimed to assess the global burden of primary liver cancer attributable to metabolic risk factors, including high body mass index (BMI) and high fasting plasma glucose (FPG) levels, between 1990 and 2021., Methods: The total number and age-standardized rates of deaths and disability-adjusted life years (DALYs) from primary liver cancer attributable to each metabolic risk factor were extracted from the Global Burden of Disease Study 1990-2021. The metabolic burden trends of liver cancer across regions and countries by sociodemographic index (SDI) and sex were estimated. The annual percentage changes in age-standardized DALYs rate were also calculated., Results: Globally, in 2021, primary liver cancer attributable to high BMI and/or high FPG was estimated to have caused 59,970 deaths (95% uncertainty interval [UI]: 20,567 to 104,103) and 1,540,437 DALYs (95% UI: 540,922 to 2,677,135). The age-standardized rates of death and DALYs were 0.70 (95% UI: 0.24 to 1.21) and 17.64 (95% UI: 6.19 to 30.65) per 100,000 person-years. A consistent global rise in liver cancer attributable to metabolic risks was observed from 1990 to 2021, with high BMI identified as the major contributing risk factor. The highest burden of deaths and DALYs of liver cancer consistently occurred in high SDI countries, while the fastest growth trends were observed in low-middle SDI countries. The burdens of high levels of BMI and FPG were higher in men than in women., Conclusions: Primary liver cancer attributable to high BMI and/or high FPG imposes an increasingly substantial clinical burden on global public health, particularly in high SDI countries. Rapid growth trends are also found in middle-SDI countries., (Copyright © 2025 by The American College of Gastroenterology.)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important public health threat, potentially leading to chronic liver disease and liver cancer. Current guidelines recommend using the FIB-4 score for initial identification of subjects at risk of future complications. We formulate a novel population screening strategy based on the Steatosis-Associated Fibrosis Estimator (SAFE) score, recently developed for MASLD risk stratification in primary care., Methods: We interrogated the National Health and Nutrition Examination Survey data, 2017-20, in which a sample of subjects representative of US civilian population underwent vibration controlled transient elastography (VCTE). The current guideline and a new, SAFE-based proposal were applied to these data to project the number of subjects to be diagnosed with liver fibrosis gauged by liver stiffness measurement (LSM), including significant (LSM ≥8kPa) and advanced (LSM ≥12kPa) fibrosis, as well as the number of VCTEs to be performed., Results: In the survey data, 2,691 subjects, projecting to 75.8 million US adults, were found to have MASLD, of whom 11% had LSM 8-12kPa and 6% LSM ≥12kPa. When the current guideline was applied, 18.1 million VCTEs would be needed to diagnose 3.5 million subjects with LSM ≥8kPa and 1.7 million subjects with LSM ≥12kPa. In comparison, a new approach based on the SAFE score would detect 4.9 million with LSM ≥8kPa and 2.5 million subjects with LSM ≥12kPa (37% and 45% improvement over the current guideline, respectively), while requiring 5.0 million fewer VCTEs (28% reduction)., Conclusion: The proposed population risk stratification approach using the SAFE score is simpler and substantially more effective, yielding more subjects with liver fibrosis while requiring less resources compared to the currently recommended algorithm., (Copyright © 2025 by The American College of Gastroenterology.)

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus. It is diagnosed in the setting of symptoms of esophageal dysfunction and an eosinophilic predominant infiltrate in the esophagus. The condition is rapidly increasing in incidence and prevalence and is commonly encountered in gastroenterology and allergy practices, emergency departments, and primary care settings. Over the past decade, there have been paradigm shifts in disease diagnosis and management, increases in knowledge about EoE risk factors, natural history, and pathogenesis, and development of validated outcome metrics. This updated American College of Gastroenterology Clinical Guideline uses Grading of Recommendations, Assessment, Development, and Evaluation methodology to make recommendations across domains of diagnosis, treatment, monitoring and assessment of response, and pediatric-specific considerations. Proton pump inhibitors, topical steroids, empiric diet elimination, a biologic, and esophageal dilation are all recommended treatments; feeding therapy is used adjunctively in children with food aversion or feeding dysfunction. Monitoring with clinical, endoscopic, and histologic assessments is recommended to assess for treatment response and follow patients over time with maintenance therapy. When evaluating and following patients with EoE, consideration should be given to assessing and controlling both the inflammatory and fibrostenotic aspects of disease., (Copyright © 2024 by The American College of Gastroenterology.)

Gastroesophageal reflux disease occurs when the barrier at the esophagogastric junction is weakened, allowing for transient relaxations of the lower esophageal sphincter or disruption of the esophagogastric junction. This leads to the refluxate traveling up the esophagus, and potentially into the pharynx, where it can be aspirated into the airway. The refluxate can cause a range of symptoms, including sore throat, coughing, wheezing, and shortness of breath, which may occur with or without visible airway inflammation. Both experimental and clinical studies have shown that aspirated refluxate can directly damage the airway lining and trigger immune responses that contribute to airway injury and inflammation. While traditional diagnostic tests for gastroesophageal reflux disease can identify abnormal reflux patterns, there is a need for more specific methods to predict airway inflammation or therapeutic outcomes related to reflux aspiration., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Endoscopy, standard-of-care for monitoring eosinophilic esophagitis (EoE), assesses mucosal inflammation. The Esophageal String Test (EST), a minimally invasive swallowed capsule and immunoassays, quantifies EoE inflammation. We determined whether the EST/EoEScore can monitor disease in patients undergoing treatment., Methods: Thirty-three samples from 14 patients with EoE (7 children, 7 adults) who underwent repeat endoscopies and ESTs were studied. Biopsies were analyzed for peak eosinophil counts; ESTs were analyzed for EoEScores., Results: Eosinophil counts and EoEScores significantly correlated during treatment, distinguishing patients with active EoE from treatment-associated remissions for 93.9% of ESTs performed., Discussion: The EST can be used to longitudinally monitor responses to treatment in EoE., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Pouchitis and Crohn's-like disease of the pouch (CLDP) are common in patients who undergo ileal pouch anal anastomosis for ulcerative colitis. We conducted separate systematic reviews to evaluate the effectiveness of available interventions to prevent and treat pouchitis and CLDP., Methods: Through systematic literature reviews, we identified studies that evaluated the effectiveness of probiotics, antibiotics, 5-aminosalicylates, nonsystemic oral corticosteroids, and advanced therapies for prevention and treatment of pouchitis and CLDP for meta-analysis. Primary outcomes were occurrence of pouchitis for pouchitis prevention and clinical response for pouchitis and CLDP treatment. We estimated the relative effectiveness of these interventions using the existing placebo response rates or hypothetical spontaneous improvement rates derived from clinical trials of pouchitis, ulcerative colitis, and Crohn's disease., Results: Probiotics were effective for primary (relative risk [RR] 0.18; 95% confidence interval [CI] 0.05-0.62) and secondary prevention (RR 0.17; 95% CI 0.09-0.34) of pouchitis. Antibiotics were effective for treatment of acute and chronic pouchitis (12 cohorts; RR 1.67; 95% CI 1.34-2.01; response rate 65%; 95% CI 52-75) with ciprofloxacin and metronidazole-based regimens being more effective than rifaximin. Advanced therapies were effective for treatment of chronic antibiotic-refractory pouchitis (31 cohorts; RR 1.71; 95% CI 1.28-2.56; response rate 50%; 95% CI 43-57) and CLDP (10 cohorts; RR 2.49; 95% CI 1.87-3.73; response rate 74%; 95% CI 68-79) without significant difference between classes., Discussion: Multiple medical interventions are effective for prevention and treatment of pouchitis and CLDP. Given the overall low quality of data, further research is needed to confirm these findings., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Little is known about how patients make decisions about and prioritize therapies and disease management in eosinophilic esophagitis (EoE). We aimed to systematically identify and characterize patient perspectives and attitudes that influence decision making for EoE management., Methods: To understand the diverse attitudes and values of patients with EoE, we designed a study using the Q-method. We iteratively developed 31 statements related to EoE disease management. Participants sorted statements by ranking from +4 (most agree) to -4 (most disagree). By-person factor analysis, using 2-factor and 3-factor rotation, revealed distinct preference archetypes., Results: Thirty-four adults with EoE (mean age 40.9 years, 51.4% male, 82.9% White) were recruited from gastroenterology and allergy clinics from a single center. We identified 2 treatment-centered archetypes: Medication preference, driven by symptoms and the desire to minimize risk of complications and Natural treatment preference , focusing on identifying trigger foods and diet adherence. Three-factor analysis revealed an additional archetype: Treatment ambivalent, a view of EoE as a mild and episodic (not chronic) disease with low priority to treat. Comparison by factor revealed 54% of those in the natural preference archetype were recategorized as treatment ambivalent , suggesting that they see natural treatment as a less complicated or milder strategy and may be at risk of nonadherence and reduced treatment uptake., Discussion: We identified 3 distinct treatment preference archetypes among individuals with EoE, underscoring the need for personalized treatment strategies, especially for those favoring natural approaches but masking ambivalence, and may be at risk of nonadherence or loss to follow-up., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Hospitalized patients with acute decompensation (AD) of cirrhosis are at risk of progressing to acute-on-chronic liver failure (ACLF), significantly increasing their mortality. The aim of this study was to identify key predictors and patient trajectories predisposing to ACLF., Methods: In this multicenter, prospective study spanning 2 years, clinical, biochemical, and 90-day survival data were collected from 625 patients with AD (European Association for the Study of the Liver criteria) across North, South, and East India. We divided the cohort into a Derivation cohort (DC: 318 patients) and a Validation cohort (VC: 307 patients). Predictive models for pre-ACLF were derived, validated, and compared with established scores such as model for end-stage liver disease (MELD) 3.0 and chronic liver failure Consortium acute decompensation., Results: Of 625 patients (mean age 49 years, 83% male, 77.5% with alcohol-related liver disease), 32.2% progressed to ACLF. Patients progressing to ACLF showed significantly higher bilirubin (10.9 vs 8.1 mg/dL), leukocyte counts (9,400 vs 8,000 per mm 3 ), international normalized ratio (1.9 vs 1.8), and MELD 3.0 (28 vs 25) but lower sodium (131 vs 134 mEq/L) and survival (62% vs 86%) compared with those without progression ( P < 0.05) in the DC. Consistent results were noted with alcohol-associated hepatitis, infection and hepatic encephalopathy as additional risk factors in VC. Liver failure at presentation (odds ratio: 2.4 [in DC], 6.9 [in VC]) and the 7-day trajectories of bilirubin, international normalized ratio, and MELD 3.0 significantly predicted ACLF progression ( P < 0.001). A new pre-ACLF model showed superior predictive capability (area under the curve of 0.71 in DC and 0.82 in VC) compared with MELD 3.0 and chronic liver failure Consortium acute decompensation scores ( P < 0.05)., Discussion: Approximately one-third of AD patients in this Indian cohort rapidly progressed to ACLF, resulting in high mortality. Early identification of patients at risk can guide targeted interventions to prevent ACLF., (Copyright © 2024 by The American College of Gastroenterology.)

Inflammatory bowel disease (IBD)-associated spondyloarthritis (SpA) is common but remains poorly understood. In this review article, we aimed to provide guidance regarding the diagnosis and management of this condition. For diagnosis of IBD-associated peripheral SpA (IBD-pSpA), we recommend collaboration with rheumatology for incorporation of clinical symptoms, physical examination findings, joint imaging if applicable, and available diagnostic criteria. For the management of IBD-pSpA, we first recommend assessment and treatment of underlying luminal IBD disease activity. We provide guidance regarding positioning of advanced therapies for IBD in patients with IBD-pSpA based on the limited available literature. For diagnosis of IBD-associated axial SpA, we recommend rheumatology referral to make the diagnosis based on incorporation of symptoms, laboratory data, imaging findings (sacroiliitis), and available diagnostic criteria. For the management of axial SpA, we recommend comanagement with rheumatology and use of either antitumor necrosis factor agents or Janus kinase inhibitors, when applicable., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: The management strategies for eosinophilic esophagitis include proton pump inhibitors (PPIs), swallowed topical corticosteroids (tCSs), elimination diets, and the biologic agent dupilumab, although there remains little guidance on the selection of initial treatment. We performed cost-effectiveness analyses to compare these approaches of first-line therapy., Methods: A Markov model was constructed from a payer perspective to evaluate the cost-effectiveness of first-line therapies for eosinophilic esophagitis, including PPI, tCS, and 6-food elimination diet (SFED), with crossover in treatments for primary and secondary nonresponse. The primary outcome was incremental cost-effectiveness ratio at 2 and 5-year time horizons. Secondary analyses included modeling from a societal perspective that also accounted for patient-specific costs, as well as a separate simplified model comparing dupilumab with tCS and PPI., Results: In the base-case scenario (5-year time horizon), the average costs were SFED: $15,296.81, PPI: $16,153.77, and tCS: $20,975.33 as initial therapy, with SFED being the dominant strategy (more effective/less costly), while PPI offered the lowest cost on a 2-year time horizon. From a societal perspective, PPI was the dominant initial strategy on both 2 and 5-year time horizons. Among pharmacologic therapies, PPI was the most cost-effective first-line option. Dupilumab was not cost-effective relative to tCS, unless the quarterly cost is reduced from $7,311 to $2,038.50 per price threshold analysis under permissive modeling conditions., Discussion: SFED was the most effective/least costly first-line therapy from the payer perspective while PPI was more cost-effective from the societal perspective. PPI is also the most cost-effective pharmacologic strategy. Dupilumab requires substantial cost reductions to be considered cost-effective first-line pharmacotherapy., (Copyright © 2024 by The American College of Gastroenterology.)

The concept of using diet as therapy in inflammatory bowel disease is of interest to clinicians and patients. Once considered to play a minor role, diet is now known to not only affect disease onset but may also serve as a therapeutic tool for inducing and maintaining remission and improving surgical outcomes. Further research is needed to fully elucidate how, when, and in whom diet therapies may be best applied to improve clinical and disease outcomes. The aim of this review was to summarize current research findings and serve as a tool to help facilitate patient-clinician conversations., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: In patients with inflammatory bowel disease (IBD), co-occurring spondyloarthritis (SpA) leads to poorer outcomes and impaired quality of life, highlighting the importance of early detection and effective treatment. This is the first study to assess the prevalence and distribution of axial symptoms and magnetic resonance imaging (MRI)-detected involvement of the spine and sacroiliac joints (SIJs) in early IBD., Methods: Newly diagnosed patients with IBD from a prospective, population-based cohort were consecutively recruited. Rheumatological interview, clinical, ultrasound, and MRI assessment for SIJ and spine inflammatory and structural lesions were made using validated scoring methods and consensus definitions of axial SpA (axSpA)., Results: Of 110 patients (ulcerative colitis: 70, Crohn's disease: 40, mean age of 42 years, and 40% male), 48 (44.9%) reported back and/or buttock pain, and 10 (9.1%) had inflammatory back pain. Seventeen (16.7%) patients had MRI findings indicative of axSpA; only 10 of these patients had axial symptoms. Inflammatory MRI lesions were present in SIJs and the spine of 27 (26.5%) and 30 (30.3%) patients, respectively. The Assessment of SpondyloArthritis International Society classification criteria for axSpA were met in 11 (10%) cases. MRI findings typical of axSpA were associated with peripheral joint and entheseal inflammation detected by ultrasound ( P = 0.04). No differences in clinical or imaging findings were found between patients with ulcerative colitis and Crohn's disease., Discussion: One-in-6 newly diagnosed patients with IBD had MRI findings indicative of axSpA. As 40% of these patients were asymptomatic, this suggests that axSpA is underdiagnosed in early IBD. Multidisciplinary collaboration is essential to ensure early detection of axial inflammation and to enable optimal therapy preventing future structural damage and disability., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photographs of patients with UC (DLSUC) to predict endoscopic mucosal inflammation., Methods: This was a prospective multicenter study conducted in 6 tertiary referral hospitals. Patients scheduled to undergo endoscopy for mucosal inflammation monitoring were asked to take photographs of their stool using smartphones within 1 week before the day of endoscopy. DLSUC was developed using 2,161 stool pictures from 306 patients and tested on 1,047 stool images from 126 patients. The UC endoscopic index of severity was used to define endoscopic activity. The performance of DLSUC in endoscopic activity prediction was compared with that of fecal calprotectin (Fcal)., Results: The area under the receiver operating characteristic curve (AUC) of DLSUC for predicting endoscopic activity was 0.801 (95% confidence interval [CI] 0.717-0.873), which was not statistically different from the AUC of Fcal (0.837 [95% CI, 0.767-0.899, DeLong P = 0.458]). When rectal-sparing cases (23/126, 18.2%) were excluded, the AUC of DLSUC increased to 0.849 (95% CI, 0.760-0.919). The accuracy, sensitivity, and specificity of DLSUC in predicting endoscopic activity were 0.746, 0.662, and 0.877 in all patients and 0.845, 0.745, and 0.958 in patients without rectal sparing, respectively. Active patients classified by DLSUC were more likely to experience disease relapse during a median 8-month follow-up (log-rank test, P = 0.002)., Discussion: DLSUC demonstrated a good discriminating power similar to that of Fcal in predicting endoscopic activity with improved accuracy in patients without rectal sparing. This study implies that stool photographs are a useful monitoring tool for typical UC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Statin-induced liver injury has been widely described. However, cases of clinically significant liver injury are rare. We present a 56-year-old woman who developed atorvastatin-induced grade III acute liver injury with concurrent rhabdomyolysis that worsened after rechallenging, which highlighted the need for pharmacovigilance with statins. The Roussel Uclaf Causality Assessment Method and Revised Electronic Causality Assessment Method both showed that atorvastatin was highly probable in causing hepatotoxicity. To our knowledge, this is the first reported case of concurrent drug-induced liver injury and rhabdomyolysis after a positive rechallenge with atorvastatin., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Anorectal mucosal melanoma (ARMM) is exceptionally rare, highly malignant, and characterized by a poor prognosis. We present the case of a 76-year-old woman with ARMM and recurrent gastrointestinal (GI) bleeding/anemia caused by small-bowel metastases, which was successfully managed with laparoscopic resection. ARMM is an aggressive type of cancer that has the potential to metastasize to the GI tract approximately 4.5 years after the primary diagnosis. Intussusception and GI bleed are potential complications. Small-bowel metastatic melanoma typically goes undiagnosed until autopsy and requires a multidisciplinary approach. Key treatment options include surgery and immunotherapy to improve patient outcomes., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Immune checkpoint inhibitors commonly cause gastrointestinal immune-related adverse effects. These patients also carry an increased risk of concomitant infections. This 66-year-old man with immune checkpoint inhibitor colitis was discovered to have concurrent Yersinia and Cytomegalovirus colitis. Such infections may mimic or complicate disease course. Hence, clinicians must monitor patient symptoms, have a low threshold for infectious testing and colonoscopy, and consider treatment strategies to mitigate their risk., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Long-acting injectable formulation of cabotegravir/rilpivirine (CAB/RPV) is a promising novel maintenance therapy for HIV infection. However, coinfection with active hepatitis B virus (HBV) infection is a contraindication to initiating this therapy. Despite guidelines, patients with HBV immunity can still contract acute HBV infection. We report a case of a 30-year-old man with HIV who transitioned from antiretroviral therapy to CAB/RPV and had confirmed HBV immunity. The patient, though asymptomatic, showed significantly elevated liver function tests (LFTs) before his monthly CAB/RPV injection. He was hospitalized and diagnosed with acute HBV infection. His LFTs improved, and he was taken off CAB/RPV and returned to antiretroviral therapy for the treatment of HIV and HBV. During subsequent follow-ups as an outpatient, the patient's LFTs normalized, and his HBV viral load significantly decreased. This case highlights the potential need for routine HBV testing in patients on CAB/RPV therapy., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Hepatitis B virus (HBV) infection is regarded as a major health concern worldwide. In patients with chronic HBV infection, exhausted virus-specific CD8+ T cells, resulting from the activation of the programmed cell death protein 1 and programmed death ligand 1 axis, play a key role in the chronicity of infection. Functional cure for HBV, defined as the seroclearance of hepatitis B surface antigen (HBsAg), is viewed as the optimal goal of chronic HBV infection treatment because HBsAg loss is associated with a low risk of hepatocellular carcinoma and a relatively favorable prognosis. Both interferon treatment and finite antiviral therapy have been found to be associated with positive HBV outcomes. Overall, combining immune checkpoint inhibitors with nucleos(t)ide analogs appears to be a promising approach for achieving HBsAg loss, particularly in patients with low HBsAg levels., Competing Interests: Conflict of interest: Dr. Yi-Hsiang Huang, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Abstract: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people with HIV (PWH) and increases the risk of hepatic fibrosis and hepatocellular carcinoma. We sent an online survey to providers of the American Academy of HIV Medicine. Of respondents (n = 214, 8% response rate), 65% reported screening for NAFLD in PWH, with 28% routinely screening all patients. Most respondents refer patients to hepatology if workup suggests another coexisting liver disease or cirrhosis, with the primary goals of referral being additional diagnostic testing (60%) or specific treatments (75%). The most common barriers to screening were feeling unsure of what tests to order (28%) and how to conclusively diagnose NAFLD (29%). Most respondents were interested in society guidelines (73%) and NAFLD education for patients (57%) and providers (55%). Our findings support the development of NAFLD clinical practice guidelines for HIV providers and the inclusion of PWH in clinical trials of novel agents., (Copyright © 2024 Association of Nurses in AIDS Care.)

Introduction: Nationwide, population-based data on the risk of extrahepatic malignancy in patients with autoimmune hepatitis (AIH) in Asian countries are scarce. This study aimed to examine the risk of developing extrahepatic malignancies in a nationwide cohort of patients with AIH., Methods: Using claims data from the Korean National Health Insurance Service database, patients diagnosed with AIH between 2007 and 2019 (n=7,382) were matched in a 1:8 ratio with an age- and sex-matched control population (n=58,320). We compared the incidence rates (IRs) and hazard ratios (HRs) of overall and specific extrahepatic malignancies between the two groups, while also examining the impact of immunosuppressant use., Results: During a median follow-up period of 5.2 years, a total of 3,713 extrahepatic malignancies developed. The IR of extrahepatic malignancy in AIH patients (990.8 cases per 100,000 person-years) was comparable to that in the matched controls (937.6 cases per 100,000 person-years), with an HR of 0.93 (95% CI, 0.81-1.07; P = 0.30). However, a significantly higher risk of hematologic malignancies, particularly lymphoma or myeloma (HR, 2.66; 95% CI, 1.70-4.17; P<0.001), was observed. The use of glucocorticoids (HR, 0.74; 95% CI, 0.31-1.75; P=0.50) or azathioprine (HR, 2.12; 95% CI, 0.90-5.02; P=0.09) had no impact on the risk of lymphoma or myeloma in patients with AIH., Discussion: In this nationwide, population-based cohort, AIH was not associated with an increased risk of overall extrahepatic malignancy compared with age- and sex-matched controls. However, AIH itself increased the risk of lymphoma or myeloma, independent of immunosuppressant use., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Because biologic and small molecule therapy is expensive, payors have mandated pre-authorizations for these medications, often resulting in a lengthy approval process. The aims of this study are to assess the frequency of and risk factors for delays in starting advanced therapies assessing insurance, care team, and patient-related factors., Methods: Retrospective, multi-center study of adult inflammatory bowel disease patients with prescriptions for an advanced therapy in two geographically distinct academic gastroenterology practices; one with and the other without a dedicated pharmacist. A priori we defined a delay in starting therapy as >14 days between prescription and first dose. Logistic regression analysis was performed to assess for risk factors for delay., Results: A total of 388 patients were prescribed advanced therapies with 46.6% receiving their first dose within 14 days. Patients who were on time vs delayed were similar in baseline demographics, disease characteristics, and disease activity. After adjusting for confounders, three independent risk factors remained significant as predictors for delay; study site (OR=5.2, 95% CI 2.894, 9.333), intravenous drug delivery as opposed to subcutaneous or oral (OR=3.07, 95% CI 1.845, 5.099), and insurance denial (OR=2.72, 95% CI 1.082, 6.825)., Conclusions: In a multicenter study, we found that a delay between prescription and administration of first dose of an advanced therapy is common, with >50% of patients having the first dose delayed by >2 weeks. Delays in starting therapy were significantly more likely if denied by insurance, given via IV induction, or at a study site without a dedicated pharmacist., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Endoscopic full-thickness resection (EFTR) is a novel endoscopic technique for removing complex colorectal lesions. The inflammatory bowel disease (IBD) population poses unique challenges for endoscopic resection due to an increased prevalence of fibrotic, nonlifting lesions and higher recurrence rates compared with the general population. This case series reports on the successful use of EFTR in 5 patients with IBD who had challenging colonic polyps, including fibrotic and nonlifting lesions. Technical success was achieved in all cases without any postoperative complications. Follow-up surveillance revealed no residual lesions or recurrence, and histopathological analysis confirmed full-thickness resection in all samples. This is one of the first case series suggesting that EFTR is a promising, safe, and effective alternative to surgery for managing complex colorectal polyps in patients with IBD., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Recent advancements in Artificial Intelligence (AI), particularly through the deployment of Large Language Models (LLMs), have profoundly impacted healthcare. This study assesses five LLMs-ChatGPT 3.5, ChatGPT 4, BARD, CLAUDE, and COPILOT-on their response accuracy, clarity, and relevance to queries concerning acute liver failure (ALF). We subsequently compare these results with Chat GPT4 enhanced with Retrieval Augmented Generation (RAG) technology., Methods: Based on real-world clinical use and the American College of Gastroenterology guidelines, we formulated 16 ALF questions or clinical scenarios to explore LLMs' ability to handle different clinical questions. Using the "New Chat" functionality, each query was processed individually across the models to reduce any bias. Additionally, we employed the RAG functionality of GPT-4, which integrates external sources as references to ground the results. All responses were evaluated on a Likert scale from 1 to 5 for accuracy, clarity, and relevance by four independent investigators to ensure impartiality., Result: ChatGPT 4, augmented with RAG, demonstrated superior performance compared to others, consistently scoring the highest (4.70, 4.89, 4.78) across all three domains. ChatGPT 4 exhibited notable proficiency, with scores of 3.67 in accuracy, 4.04 in clarity, and 4.01 in relevance. In contrast, CLAUDE achieved 3.04 in clarity, 3.6 in relevance, and 3.65 in accuracy. Meanwhile, BARD and COPILOT exhibited lower performance levels; BARD recorded scores of 2.01 in accuracy and 3.03 in relevance, while COPILOT obtained 2.26 in accuracy and 3.12 in relevance., Conclusion: The study highlights Chat GPT 4 +RAG's superior performance compared to other LLMs. By integrating RAG with LLMs, the system combines generative language skills with accurate, up-to-date information. This improves response clarity, relevance, and accuracy, making them more effective in healthcare. However, AI models must continually evolve and align with medical practices for successful healthcare integration., (Copyright © 2024 by The American College of Gastroenterology.)

Background and Aims: Gastrointestinal (GI) symptoms and weight loss develop during and after acute pancreatitis (AP), but remain understudied. In this prospective, multicenter study, we aim to assess GI symptom burden and weight loss and their correlation with exocrine function up to 12-mo post-AP., Methods: GI symptom burden, anthropometrics, and exocrine pancreatic function were systematically measured in adults (≥18 years) with AP at predefined intervals: hospitalization (enrollment), 3-months (3-mo), and 12-mo post-AP. Symptoms were evaluated using a 15-item tracker, including abdominal symptoms, stool characteristics, and activities of daily living; higher scores indicating greater symptom burden (range 0-45). Exocrine function was assessed with fecal elastase-1 (FE-1) levels., Results: GI symptoms were collected in 97 participants with 12-mo follow-up. The median (IQR) GI-symptom score was 7 (3-12) with 55 participants (57%) experiencing at least one symptom frequently ("often" or "almost always"). In multivariable linear regression, younger age, lower Charlson Comorbidity Index, smoking, recurrent AP, and alcoholic or idiopathic etiologies were associated with significantly higher GI-symptom burden at 12-mo. A significant negative correlation was found between GI symptoms and FE-1 levels during hospitalization ((ρ)=-0.288; p=0.015) and at 12-mo (ρ=-0.219; p=0.046). Eighteen participants (18.6%) lost ≥10% body weight between hospitalization and 12-mo, and had significantly lower median FE-1 levels at 12-mo compared to the group without weight-loss (166 vs. 332 µg/g, p=0.016)., Conclusions: This is the first study to prospectively assess GI-symptom burden and exocrine function post-AP. Lower exocrine pancreatic function at 12-mo was associated with increased symptom burden and weight loss. These findings support further investigations to define and improve patient-reported outcomes post-AP., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Acute illness states with increased metabolic demand can precipitate severe thiamine deficiency if physiologic needs exceed endogenous stores and supplementation. Patients with preexisting risk factors such as parenteral nutrition (PN) dependence, eating disorders, gastrointestinal disorders, or surgeries are especially vulnerable., Case Summary: A 9-year-old girl with short bowel syndrome receiving long-term PN, including standard thiamine supplementation, presented with refractory shock following aspiration. Profound hyperlactatemia, cardiac dysfunction, and vasoactive requirements persisted despite extracorporeal membrane oxygenation and resolved only after treatment with parenteral thiamine., Conclusions: Hemodynamic collapse due to thiamine deficiency (Shoshin beriberi) may occur during acute illness in children with nutritional risk factors and should be considered in refractory hyperlactatemia. Timely treatment with parenteral thiamine can support dramatic hemodynamic recovery. Treatment of suspected thiamine deficiency should not be delayed for laboratory confirmation as current thiamine reference ranges correlate poorly with clinical severity, and functional testing may not be readily available., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction: We explored the clinical characteristics, treatment, and outcomes of colitis-associated colorectal cancer (CAC) and compared with sporadic colorectal cancer in Taiwan., Methods: In this retrospective study spanning 1987-2022, CACs diagnosed according to endoscopic and pathological reports from 14 tertiary centers were reported to our cohort. Clinical demographics, endoscopic findings, histological results, treatment modalities, and outcomes were analyzed. Sporadic colorectal cancer data were retrieved from the Cancer Registry Annual Report, Ministry of Health and Welfare, Taiwan., Results: We enrolled 65 patients with CAC (median age: 56 years; male: 66.2%). Distal colon was the most common tumor location (41.5%). Of patients with ulcerative colitis, 77.2% had extensive colitis, and 76.5% had Mayo endoscopic subscores of ≥2. Moreover, 50% of lesions were nonpolypoid with indistinct borders in 66.7%. Signet-ring cell subtype consisted of 12.3%. Surveillance colonoscopy adherence was 78.4%, yet 51.3% interval cancers occurred. Disease stage 0-4 distribution was 15%, 20%, 13.3%, 20%, and 31.7%, respectively. Endoscopic resection was feasible for 14%, whereas 67.7% required surgery. During follow-up (median: 21.5 months), we recorded 23.2% recurrence and 34.5% mortality. Lesions with indistinct borders were associated with adverse outcomes (adjusted odds ratio = 11.5 [1.35-98.16]). Colitis-associated rectal cancers, diagnosed later ( P < 0.001), had worse outcomes than sporadic rectal cancers., Discussion: This is the largest Asian CAC cohort study, emphasizing the need for stringent disease control, improving detection, and reducing interval cancers. Signet-ring cell subtype was prevalent. Rectal colitis-associated cancers were diagnosed later with poorer outcomes than sporadic rectal cancers., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Abstract: Patients with cirrhosis are at risk of developing hepatic encephalopathy, which can present with a wide range of symptoms, including confusion, lethargy, inappropriate behavior, and altered sleep patterns. In addition to hepatic encephalopathy, patients with cirrhosis are at risk of developing mild cognitive impairment, dementia, and delirium, which have features closely resembling hepatic encephalopathy. Given the similar presentation of these conditions, misdiagnosis can and does occur. Mild cognitive impairment is common in individuals aged ≥50 years and can progress to dementia in those affected. Dementia and hepatic encephalopathy are both characterized by sleep disturbance and cognitive dysfunction, thus differentiating these conditions can be difficult. Furthermore, delirium can disrupt sleep patterns, and liver disease is recognized as a risk factor for its development. As hepatic encephalopathy is a cirrhosis-related complication, determining if a patient has undiagnosed cirrhosis is critical, particularly given the large number of patients with asymptomatic, compensated cirrhosis. Separately, underdiagnosis of minimal hepatic encephalopathy can occur even in patients with diagnosed liver disease, related, in part, to lack of testing. Given the availability of effective therapies available for managing symptoms and preventing future episodes, accurate diagnosis of hepatic encephalopathy is essential., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

The diagnosis and monitoring of eosinophilic esophagitis (EoE) relies on clinical symptoms and histological examination of the esophageal mucosa. Currently, esophagogastroduodenoscopy with biopsy is the standard of care in the diagnosis and monitoring of EoE. Unsedated transnasal endoscopy (TNE) is a less invasive and less costly procedure that can be performed without general anesthesia. Here, we describe the first case of a 15-year-old adolescent girl who underwent TNE exclusively to identify all food triggers for EoE. She underwent 12 TNEs over a period of 4 years to identify food triggers for EoE to ultimately achieve the remission of her disease., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Corticosteroids are recommended by multiple society guidelines for the treatment of severe alcohol-associated hepatitis (AH). However, their use remains controversial due to inconsistent studies regarding their survival benefit., Methods: This was a retrospective cohort study of first-time hospitalizations for severe AH (Maddrey discriminant function ≥ 32) admitted to the Veterans Health Administration between January 3, 2005, and December 5, 2020, (i) evaluating the effect of corticosteroid therapy on all-cause survival, (ii) characterizing the clinical and psychosocial factors associated with corticosteroid use, and (iii) determining the effect of duration of corticosteroid therapy on all-cause survival among treatment-responsive patients (Lille score < 0.45)., Results: During the study period, 2,618 patients were admitted with severe AH, of whom 1,083 (41.37%) received corticosteroids. Although corticosteroids were significantly associated with improved all-cause survival in the unadjusted model ( P = 0.022), no survival benefit was observed in the adjusted model after accounting for baseline and admission characteristics (adjusted hazard ratio [aHR] = 1.01, P = 0.818). Psychiatry consultation was the only factor evaluated that was protective against mortality (aHR = 0.67, P < 0.001). Among the 428 patients (49.7%) responsive to corticosteroids, duration of therapy was not associated with overall survival on unadjusted ( P = 0.696) or adjusted models (aHR = 1.12, P = 0.710 for a ≥28-day course compared with a ≤7-day reference)., Discussion: Despite being recommended by clinical guidelines for severe AH, corticosteroids have low utilization with no survival benefit after accounting for differences in patient characteristics and practice patterns. Among patients with treatment response per the Lille score, no difference was observed in overall survival between shorter and longer durations of corticosteroid therapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: The increasing prevalence of clarithromycin (CLA)-resistant Helicobacter pylori(H. pylori) strains poses a significant challenge in the management of H. pylori infections. This systematic review and meta-analysis investigates the diagnostic accuracy of polymerase chain reaction (PCR) in identifying CLA-resistant H. pylori strains in stool., Methods: A comprehensive literature search was conducted using PubMed, Embase, and Cochrane databases from database inception to April 30, 2023. Eligible studies evaluated the effectiveness of PCR stool tests in detecting CLA-resistant H. pylori strains in adults (>18-year-old). Studies of pediatric populations, alternative methods to PCR or stool samples, and reference tests other than gastric biopsy were excluded. The bivariate random-effects model was used to pool diagnostic accuracy from the included studies., Results: The analysis of 11 prospective diagnostic studies with a total of 866 patients showed a pooled sensitivity of 0.97 (95% CI: 0.9-0.99) and a pooled specificity of 0.98 (95% CI: 0.81-1.00). Subgroup analysis based on the used technique demonstrated consistent findings without notable variations. The diagnostic odds ratio was calculated at 1843.92 (95% CI: 134.28-25,321.3). The positive likelihood ratio was determined as 51.02 (95% CI: 4.61-564.5), while the negative likelihood ratio was found to be 0.03 (95% CI: 0.01-0.1)., Discussion: PCR testing for clarithromycin-resistant H. pylori was highly sensitive and specific across studies with proven reliability in clinical practice, particularly in outpatient settings. Their implementation offers cost-effectiveness and the potential for tailored treatment strategies, holding promise for improved patient outcomes., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications., Methods: Results for the phase 3 LIBERTY EoE TREET study co-primary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses., Results: A steep initial relationship then plateau was observed between higher dupilumab steady state trough concentrations (Ctrough) and decreased eosinophilic infiltration at Week 24, while a graded exposure-response relationship was observed for symptomatic improvement at Week 24. Patients with the highest exposures were more likely to achieve greater symptomatic benefit, independent of strictures or history of dilation., Conclusions: The dupilumab 300 mg qw regimen approved for adults and adolescents with EoE weighing ≥40 kg is supported by dose- and exposure-response relationships., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is effective and safe in benign and malignant indications. However, there is a paucity of literature on the outcomes of these patients. Our study evaluates the long-term outcomes of patients who underwent EUS-GE and stent-related adverse events (AEs)., Methods: This retrospective study was performed at a tertiary care institution from January 1, 2014, to December 31, 2022. Patients who underwent EUS-GE were included. Procedure details and outcomes were recorded. Patients were followed for at least 3 months after the procedure., Results: A total of 207 patients (50.3% male, mean age 62.3 years) underwent EUS-GE for malignant (N = 117, 56.5%) and benign (N = 90, 43.5%) indications. Overall technical success was 95.7%. Patients were followed for a mean of 406 days. Stents were removed in 25.6% of patients; common reasons include completed access for endoscopic retrograde cholangiopancreatography (N = 13, 25%), resection/resolution of gastric outlet obstruction (GOO) (N = 28, 53.8%), and surgical resection of malignant GOO (N = 8, 15.4%). EUS-GE stents remained in place in 63.6% of patients for ≥3 months and in 21% of patients for ≥1 year. Late AEs occurred in 3.4%. Among patients who were stent-dependent (N = 24, 11.6%) and underwent annual stent exchanges, no late AEs occurred., Discussion: Long-term outcomes of EUS-GE are promising with few AEs, particularly with pre-emptive annual exchanges of stents to prevent stent delamination and occlusion among patients who require long-term indwelling stents. EUS-GE plays an increasing role in access for endoscopic retrograde cholangiopancreatography in altered anatomy, acute or chronic management of benign GOO, or bridge to definitive surgery for GOO., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970, A1073V; 1073 val/val ) related to Na v 1.8, a voltage-gated sodium channel preferentially expressed on nociceptors. It was unclear whether this relationship existed for both Crohn's disease (CD) and ulcerative colitis (UC). This study evaluated a larger, carefully phenotyped IBD cohort to investigate this question., Methods: Allelic and genotypic frequencies of rs6795970 were compared among study cohorts characterized by concomitant assessment of intestinal inflammatory status and abdominal pain experience. Visceral sensory perception was performed in healthy individuals using rectal balloon distension., Results: We analyzed 416 patients with IBD (261CD:155UC) and 142 healthy controls. In the IBD cohort, 84 individuals (43CD:41UC) were determined to have hypoalgesic disease. The allelic frequency of rs6795970 was significantly higher in patients with hypoalgesic IBD when compared with other patients with IBD and healthy controls. Patients with hypoalgesic IBD were also more likely to be homozygous for this polymorphism when compared with other patients with IBD and healthy controls. Hypoalgesic CD (30% vs 12%, P = 0.004) and hypoalgesic UC (32% vs 15%, P = 0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals (n = 50), rs6795970 homozygotes (n = 11) also demonstrated reduced abdominal discomfort to rectal balloon distension., Discussion: These findings indicate that Na v 1.8 plays a key role in human visceral pain perception, and could serve as a novel diagnostic target in the management of hypoalgesic CD and UC, and potential therapeutic target for conditions associated with chronic abdominal pain., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Failure to document colonoscopy follow-up needs postpolypectomy can lead to delayed detection of colorectal cancer (CRC). Automating the update of a unified follow-up date in the electronic health record (EHR) may increase the number of patients with guideline-concordant CRC follow-up screening., Methods: Prospective pre-post design study of an automated rules engine-based tool using colonoscopy pathology results to automate updates to documented CRC screening due dates was performed as an operational initiative, deployed enterprise-wide May 2023. Participants were aged 45-75 years who received a colonoscopy November 2022 to November 2023. Primary outcome measure is rate of updates to screening due dates and proportion with recommended follow-up < 10 years. Multivariable log-binomial regression was performed (relative risk, 95% confidence intervals)., Results: Study population included 9,824 standard care and 19,340 intervention patients. Patients had a mean age of 58.6 ± 8.6 years and were 53.4% female, 69.6% non-Hispanic White, 13.5% non-Hispanic Black, 6.5% Asian, and 4.6% Hispanic. Postintervention, 46.7% of follow-up recommendations were updated by the rules engine. The proportion of patients with a 10-year default follow-up frequency significantly decreased (88.7%-42.8%, P < 0.001). The mean follow-up frequency decreased by 1.9 years (9.3-7.4 years, P < 0.001). Overall likelihood of an updated follow-up date significantly increased (relative risk 5.62, 95% confidence intervals: 5.30-5.95, P < 0.001)., Discussion: An automated rules engine-based tool has the potential to increase the accuracy of colonoscopy follow-up dates recorded in patient EHR. The results emphasize the opportunity for more automated and integrated solutions for updating and maintaining EHR health maintenance activities., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: A straightforward, reliable, and noninvasive method for predicting the development of liver-related events (LRE) in primary biliary cholangitis (PBC) has not been attained thus far. This study investigated whether serum autotaxin (ATX) could predict LRE in patients with PBC., Methods: This retrospective multicenter investigation included 190 biopsy-proven untreated patients with PBC. All subjects were followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, esophagogastric varices, ascites, and hepatic encephalopathy, was investigated in relation with ATX levels at the time of liver biopsy., Results: During the median follow-up period of 9.7 years, LRE were observed in 22 patients (11.6%). The area under the receiver operating characteristic curve and cutoff value of serum ATX for predicting LRE were 0.80 and 1.086 mg/L, respectively. Patients with serum ATX ≥1.086 had a significantly higher cumulative incidence of LRE compared with patients with ATX < 1.086 (33.3% vs 3.6%, P < 0.00001). Notably, the predictive capability of ATX for LRE in patients with PBC surpassed that of FIB-4, ALBI, APRI, and Mac-2-binding protein glycan isomer. A multivariate Cox proportional hazards model revealed ATX as an independent associated factor for LRE (hazard ratio 6.24, 95% confidence interval 1.87-20.80, P = 0.003) along with Nakanuma stage (hazard ratio 2.75, 95% confidence interval 1.52-4.99, P < 0.001). These results were closely replicated in a serologically diagnosed PBC validation cohort (n = 32)., Discussion: Serum ATX levels may serve as a predictive marker for LRE in patients with PBC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)