Introduction The global rise in inflammatory bowel disease (IBD) parallels socio-economic development, but its influence on disease epidemiology and phenotype remains unclear. We aimed to characterise IBD incidence, clinical features, and associations with socio-economic indices across newly industrialised countries. Methods This prospective population-based study spanned 16 regions in Africa, Asia, Latin America, and the Middle East from October 2021 for one year. Poisson regression estimated incidence rate ratios (IRR) for Human Development Index (HDI), Socio-demographic Index (SDI), subnational HDI, and urban population percentage. Mixed-effects models examined associations with disease phenotype, activity, and treatment. Results Of 606 incident cases (229 Crohn’s disease [CD], 348 ulcerative colitis [UC], 29 IBD-unclassified), incidence varied widely. Hong Kong had the highest crude annual incidence (IBD 7.43; CD 2.69; UC 3.44) and Vietnam the lowest (0.13; 0.04; 0.08). Urban population (per 10% increase) was associated with higher incidence of IBD (IRR 1.68), CD (1.73), and UC (1.62). HDI and SDI significantly correlated with CD (IRR 4.05 and 2.96, respectively), but not subnational HDI. Higher HDI and subnational HDI were associated with increased odds of perianal CD (adjusted OR 2.61 and 2.40). Other disease phenotype, activity, and treatment pattern were not significantly linked to any index. Conclusion Higher urbanisation and development are associated with higher IBD incidence, particularly CD, but not with disease activity at diagnosis. Notably, perianal CD was more common in regions with higher HDI and subnational HDI, suggesting an association with regional socioeconomic development. These highlight the need for region-specific early diagnosis strategies.
Background and aims The evolution of non-invasive tests of liver fibrosis during follow-up of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains difficult to interpret in clinical practice. We aimed to translate the dynamics of non-invasive tests into a personalized prediction of liver-related events (LRE) in MASLD. Methods We used the international multicentre VCTE-Prognosis cohort including adult patients with MASLD who underwent liver stiffness measurements (LSM) by vibration-controlled transient elastography. The study outcome was LRE, a composite endpoint including cirrhosis decompensation or hepatocellular carcinoma. A joint latent class model (JLCM) was used to compute dynamic predictions resulting in a personalized estimation of the risk of LRE (0-100% at chosen time horizons). Results 13,627 patients were included, with 238 LRE occurring during the median follow-up of 4.0 years (IQR: 2.1-5.9). LSM trajectory adjusted on FIB-4 and sex (longitudinal part) and age with platelets (survival part) were selected by the JLCM for LRE prediction. Calibration plots showed very good agreement between the predicted and the observed risk of LRE. The JLCM provided excellent discrimination for LRE with integrated AUROCs increasing from 88.2% at baseline to 92.2% at the 5-year follow-up visit. At the different study visits, 61-80% of the patients who experienced LRE were identified as high risk by the JLCM, versus 39-56% with LSM and 32-60% with FIB-4. Conclusion By automatically integrating and interpreting the dynamics of non-invasive tests of liver fibrosis, JLCM enables the personalised prediction of the risk of hard outcomes, rather than the imperfect evaluation of histological surrogates.
BACKGROUND:Trials on metabolic dysfunction-associated steatohepatitis (MASH) use biopsy for efficacy assessment, despite invasiveness and cost. We aimed to assess the trial-level surrogacy and association of changes in non-invasive tests (NITs), namely liver stiffness measurement (LSM), liver fat content (LFC) by magnetic resonance imaging, fibrosis-4 score (FIB-4), and Enhanced Liver Fibrosis (ELF) with histology in MASH. METHODS:We searched PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov up to February 2026 for MASH randomized controlled trials (RCTs) reporting serial NIT data and histological endpoints (fibrosis improvement without MASH worsening or MASH resolution without fibrosis worsening). NIT trial-level surrogacy of histological improvement was quantified through squared Bayesian posterior correlation of treatment effects. RESULTS:Thirty-five RCTs and 3 post-hoc analyses were included. At the trial level, treatment effects on all NITs showed probable weak correlations with histological improvement, with the exception of LFC, which displayed probable moderate surrogacy for MASH resolution without fibrosis worsening (R2 = 62%, 95%CrI 10%-95%). In contrast, variations in LSM were near-certainly associated with fibrosis improvement without MASH worsening in F4-excluded studies (OR 2.67, 95%CrI 1.33-5.12 per 30% decrease) and near-certainly associated with MASH resolution without fibrosis worsening (OR 2.46, 1.16-4.66 per 30% decrease). LFC was near-certainly associated with MASH resolution without fibrosis worsening (OR 1.92, 1.14-3.20 per 30% decrease). CONCLUSION:LFC and LSM dynamics were associated with histological response at the outcome level, but surrogacy was limited and imprecise across biomarkers. This supports a lack of consistent trial-level surrogacy, although context-specific utility remains plausible.
BACKGROUND & AIMS:Patients with short bowel syndrome and intestinal failure (SBS-IF) depend on parenteral support (PS) to meet nutritional/fluid requirements. Apraglutide, a once-weekly, long-acting glucagon-like peptide-2 analog, promotes intestinal adaptation and may reduce PS dependence. The phase 3 STARS trial evaluated the efficacy and safety of apraglutide versus placebo in SBS-IF. METHODS:In this global, phase 3, double-blind, placebo-controlled trial, eligible patients were randomized 2:1 to once-weekly subcutaneous apraglutide or placebo, stratified by remnant intestinal anatomy (stoma or colon-in-continuity [CIC]). The primary endpoint was relative change from baseline in weekly PS volume at week 24 in the overall population. Key secondary endpoints included relative PS volume change in the stoma subgroup, days off PS (overall and CIC), and enteral autonomy (CIC). A safety analysis was conducted. RESULTS:Overall, 163 patients (80 stoma, 83 CIC) were randomized and dosed. Apraglutide significantly reduced weekly PS volume from baseline versus placebo at week 24 in the overall population (mean relative change, -25.5% vs -12.5%; P =.001) and stoma subgroup (-25.6% vs -7.8%; P <.001). A higher proportion of patients receiving apraglutide versus placebo achieved reduction of ≥1 day/week of PS at week 24 (43.0% vs 27.5%; P =.040). At week 48 (CIC), in the apraglutide versus placebo arms, the proportions of patients achieving reduction of ≥1 day/week of PS and enteral autonomy were 51.8% versus 44.4% (P =.348) and 12.5% versus 7.4% (nominal P =.387), respectively. Apraglutide was well tolerated with a favorable safety profile. CONCLUSION:Once-weekly subcutaneous apraglutide significantly reduced PS requirements in patients with SBS-IF with a well-tolerated safety profile.
BACKGROUND:Regenerating islet-derived 3-alpha (REG3α) is a serum biomarker in patients with graft-versus-host disease (GVHD) linked to 6-month mortality. REG3α is produced by intestinal Paneth cells, which are implicated in Crohn's disease (CD) pathophysiology. OBJECTIVE:To assess associations between serum REG3α and progressive CD DESIGN: Serum REG3α was measured in two cross-sectional (M: Mount Sinai, L: Leuven) and a pre-diagnostic cohort (P: PREDICTS) with serial samples up to 10 years before CD diagnosis. Tissue REG3α expression was assessed via bulk RNA sequencing from paired ileal and colonic biopsies. Serum REG3α and tissue REG3α were associated with CD progression (hospitalization, surgery, steroid course, or new advanced therapy). Single-cell RNA sequencing data explored associations between REG3α expression, Paneth cell phenotypes, and CD. RESULTS:In 394 patients, high serum REG3α associated with CD progression, independent of C-reactive protein and endoscopic activity (M: HR 1.9 (95%CI 1.3-2.8); L: HR 2.9 (95%CI 1.9-4.6), both p<0.001). The association persisted in patients with mild or inactive CD. In the pre-diagnostic cohort, high serum REG3α predicted the development of CD, particularly complicated (B2/3) and surgical presentations, up to 10 years before diagnosis (P). Analysis of REG3α expression and Paneth cell transcriptomes suggested that CD is associated with loss of regenerative Paneth cell populations and enrichment in REG3α-expressing populations, suggesting a mechanism through which changes in serum REG3α associate with complicated CD. CONCLUSION:Serum REG3α holds potential as a non-invasive, prognostic biomarker in CD, independent of disease activity. High serum REG3α, even years before diagnosis, is linked to a complicated disease course.
BACKGROUND & AIMS:Primary sclerosing cholangitis (PSC) is a chronic liver disease associated with long-term ulcerative colitis (UC) and Crohn's disease (CD). We aimed to determine its prevalence, clinical features, and impact in newly-diagnosed UC and CD. METHODS:In a prospective population-based inception cohort, all adult patients with newly-diagnosed UC or CD in a defined region of Denmark (2021-2023), were offered magnetic resonance cholangiopancreatography (MRCP). Primary outcome was the prevalence of radiological PSC. Patients were followed-up prospectively for a median of 2.0 years (IQR: 1.6-2.0, range 1.0-2.0). RESULTS:Of 527 patients, 389 patients (73.8%) (UC: 242; CD: 147) underwent MRCP, of whom 31 (8.0%) were diagnosed with radiological PSC (UC: 16 [6.6%]; CD: 15 [10.2%]), while seven (1.8%; UC: 5 [2.1%] and CD: 2 [1.4%]) had non-diagnostic PSC-like lesions, yielding a combined prevalence of 9.8%. Only 51.6% (16/31) presented with abnormal liver biochemistry. PSC prevalence was higher in patients with extensive colitis (9/73 [12.3%] vs. 7/164 [4.3%], p=0.02), but did not differ by age or sex, and was associated with higher rates of IBD-related hospitalization (41.9% vs. 23.4%, p=0.03) and biological therapies (38.7% vs. 21.4%, p=0.03) during follow-up. CONCLUSION:Radiological PSC or PSC-like lesions were present in 1 in 10 patients with incident IBD, often without biochemical abnormalities. These findings suggest a higher burden of radiological PSC at IBD onset than previously anticipated, although their long-term clinical significance remains uncertain. While MRCP at IBD diagnosis may prove clinically beneficial, confirmation from long-term follow-up and cost-effectiveness analyses is required before it can be recommended for screening.
BACKGROUND AND AIMS:Gastric intestinal metaplasia (IM) and dysplasia are precursor lesions for gastric cancer (GC). This systematic review and meta-analysis examined the global prevalence and progression rates of subtypes of these understudied lesions. METHODS:We searched databases for publications reporting prevalence and progression of subtypes of IM and dysplasia among individuals undergoing endoscopy, including incomplete/complete IM, limited (antrum-restricted)/extensive (corpus-involving) IM, and low-grade dysplasia (LGD)/high-grade dysplasia (HGD). Random-effects models were used to estimate pooled prevalence and progression rates to GC. I2 statistic was used to determine heterogeneity. RESULTS:83 studies were included for prevalence and 23 for progression. The prevalence of complete IM was 11% (95% confidence interval (CI) 8-15%) and incomplete IM was 10% (6-14%), with corresponding progression rates of 1.73 (1.08-2.79) vs. 12.15 (5.28-27.94) per 1000 person-years, respectively (p <0.01). The prevalence of limited vs. extensive IM was 12% (8-17%) vs. 5% (4-8%), respectively, and corresponding progression rates were 3.31 (1.18-9.32) vs. 4.19 (0.95-18.41) per 1000 person-years (p=0.80). The prevalence of LGD was 2% (1-4%) and HGD was 0.28% (0.14-0.55%), with corresponding progression rates of 11.55 (5.93-22.47) vs. 344.48 (144.88-819.09, p <0.01). Substantial heterogeneity was observed for all estimates. CONCLUSION:While lesion subtypes with high progression risk like incomplete IM account for a large portion of the total burden of precancerous lesions, subtyping remains underutilized in clinical practice. While estimates are limited by heterogeneity, differences in progression rates between lesion subtypes support risk-stratification of these lesions within management guidelines, particularly complete vs. incomplete IM and LGD vs. HGD.
Background & Aims The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a composite tool used to stratify patients with eosinophilic esophagitis (EoE) according to severity. We assessed longitudinal changes in I-SEE scores in patients treated with budesonide orodispersible tablets (BOT) during induction and maintenance and its association with clinical outcomes. This study represents the first application of I-SEE in a cohort of EoE patients treated with BOT, the first-line pharmacological therapy in Europe. Methods We retrospectively analyzed 109 consecutive EoE adults treated with BOT for 52 weeks. I-SEE was calculated at baseline (T0), after 12-week induction (T1), and after 1-year maintenance (T2). Associations between I-SEE, baseline characteristics, disease activity and risk of dilation were explored. Results At baseline, 28%, 54%, and 17% of patients had mild, moderate, and severe I-SEE, respectively. Higher I-SEE severity was associated with fibrostenotic phenotype, prior dilation, and food impaction. After induction, 97% achieved histologic response and median I-SEE significantly decreased (P=.001). Improvements were sustained at 1 year, with 70% maintaining histologic remission (P<.001). During maintenance, I-SEE correlated with symptom burden, endoscopic activity, and peak eosinophil count (P=.001), and inversely with histologic remission. Baseline I-SEE score did not predict loss of response during maintenance. Although higher baseline I-SEE was associated with dilation risk in univariable analysis (OR, 1.11; P=.014), this association was attenuated after adjustment for fibrostenotic phenotype. Conclusions In BOT-treated EoE, I-SEE reflects multidimensional disease control over time. Higher baseline severity identifies patients with lower response rate to BOT induction and with increased risk of structural complications, supporting early combined medical and endoscopic management.
BACKGROUND AND AIMS:The human leukocyte antigen (HLA) -DQ2.5, -DQ2.2 or -DQ8 allotypes are necessary for celiac disease (CeD) development. Their distribution may vary between adults with known, previously diagnosed CeD and newly diagnosed CeD detected through screening. METHODS:In the population-based HUNT4 study, 52,588 Norwegian adults were screened for CeD, identifying 846 (376 known, 465 new biopsy-confirmed and 163 potential) cases. Anti-TG2 seropositive subjects and a random sample of 1412 controls underwent HLA-DQA1- and HLA-DQB1-sequencing to infer relevant HLA-DQ allotypes. RESULTS:All new cases were DQ2 or DQ8 positive, while 21 known cases were DQ2 and DQ8 negative, suggesting misdiagnosis. Histological reassessment confirmed the diagnosis in 5/21. After adjusting known cases to 360, DQ2.5 frequencies were 87.8% in confirmed cases, 76.7% in potential cases, and 22.9% in controls. Among DQ2.5-negative subjects, DQ8 was most frequent, with 8.5% in confirmed cases and 10.4% in potential cases. DQ2.5/DQ2.5 carried the highest risk (odds ratio [OR] 16.7, 95% confidence interval 9.7-31.4), followed by DQ2.5/DQX (OR 5.7, 4.7-7.0), DQ8/DQ8 (OR 8.8, 4.6-16.8), and DQ8/DQX (OR 2.6, 1.7-3.8). ORs for DQ2.2/DQ2.2 and DQ2.2/DQX were 3.4 (0.5-15.0) and 0.8 (0.4-1.6), respectively. No clear differences were observed between known and new cases, however ORs for DQ2.5/DQX and DQ8 were higher in new cases. CONCLUSIONS:This study found a gene-dose effect for DQ2.5, DQ8, and DQ2.2 in both known and new cases, with a fairly high proportion of DQ8 for a Nordic population. A substantial proportion of DQ2 or DQ8 negative subjects among known cases, but absent in new cases, could be attributed to historical misdiagnosis.
BACKGROUND & AIMS:Acute severe ulcerative colitis is a life-threatening manifestation of ulcerative colitis. The diagnosis typically relies on the 1955 Truelove and Witts criteria. These do not incorporate treatment history with steroids or modern advanced therapies. This Delphi panel gathered expert opinion regarding potential criteria and approaches for diagnosing acute severe ulcerative colitis in contemporary practice, including current outpatient treatment with corticosteroids or advanced therapy. METHODS:European, North American, and Asia-Pacific gastroenterologists participated in a 4-round Delphi panel and consensus meeting, forming the Refined Evaluation Framework and INvEstigations for Diagnostics in Acute Severe Ulcerative Colitis Working Group. Consensus was defined as ≥70% agreement/disagreement for Likert scale, or ≥70% homogeneity for single/multiple choice responses. RESULTS:Panelists agreed there is an unmet need for acute severe ulcerative colitis criteria in contemporary practice. Consensus was obtained that an acute severe ulcerative colitis diagnosis could be based around 3 'major' criteria (C-reactive protein ≥2× the upper limit of normal, ≥6 bowel movements in 24 hours, ≥50% bowel movements with visible blood in 24 hours) plus ≥2 'minor' criteria (low albumin, increased heart rate, nocturnal bowel movements, low hemoglobin, increased body temperature, or elevated leukocyte count) in patients treated with advanced therapy or corticosteroids. Patients on high-dose corticosteroids constitute a subgroup requiring different thresholds (C-reactive protein ≥1× upper limit of normal, ≥33% bowel movements with visible blood in 24 hours). Similar principles were agreed upon for untreated patients but without achieving consensus. Panelists agreed that endoscopy should confirm acute severe ulcerative colitis diagnosis and exclude cytomegalovirus infection and radiologic investigations should support excluding toxic megacolon. CONCLUSIONS:This consensus provides new diagnostic criteria for acute severe ulcerative colitis in the modern therapeutic era, which can be applied to patients already in receipt of outpatient treatments. These criteria include additional clinical and laboratory parameters for validation in prospective studies.
BACKGROUND & AIMS:Metabolic dysfunction-associated steatotic liver disease is a major cause of liver disease that is growing in prevalence. Typically asymptomatic, is often undiagnosed. Imaging studies, including noncontrast computed tomography (CT) scans, can detect hepatic steatosis opportunistically, but the reporting rate is unknown. We hypothesized that incidental finding of steatosis on noncontrast CT is often not reported if not specifically sought in the imaging request. METHODS:This study was a retrospective, cross-sectional, single-center analysis of abdominal noncontrast CT scans performed between 2012 and 2020 for any indication in adult subjects. Images were analyzed using an automated deep learning liver segmentation and attenuation assessment algorithm to obtain a mean volumetric liver attenuation value. Image-based steatosis was defined as mean hepatic attenuation <40 HU and compared with textual radiology reports. Manual review of a random subset of scans and reports was used to verify results. RESULTS:A total of 3646 noncontrast CT scans from 2710 adult patients were analyzed. The mean liver attenuation derived from the deep-learning algorithm was 50.4 ± 11.8 HU. Image-based steatosis was found in 480 (13.1%) scans, with a mean liver attenuation of 29.8 ± 14 HU. Radiologists reported steatosis in only 157 (32.7%) of these low-attenuation scans. Predictors of unreported steatosis included higher average liver attenuation (even if < 40 HU), high variability of fat distribution in the liver and low body mass index. CONCLUSIONS:We found that incidental hepatic steatosis in noncontrast CT is reported in a minority of scans. Incorporating artificial intelligence-based hepatic attenuation measurement in computed tomography scan reading may increase reporting rates.
BACKGROUND & AIMS:Xenobiotic-induced liver injury (XILI) remains a challenge in hepatology, with acetaminophen (APAP) as a leading contributor to severe disease. We used national poison center surveillance to characterize long-term trends in XILI and APAP- and alcohol-associated liver injury in the United States. METHODS:A retrospective analysis of the National Poison Data System was conducted to identify reported xenobiotic exposures involving individuals aged ≥15 years from 2000 to 2024 with biochemical evidence of hepatocellular injury, defined by aspartate or alanine aminotransferase elevations >100 U/L. Exposures were stratified by sex, age, substance type, exposure intent and acuity, level of care, and medical outcome. Two secondary analyses restricted to single-substance, single-ingredient APAP (APAP-alone) and single-substance alcohol exposures were performed using the same approach. RESULTS:A total of 220,160 xenobiotic exposures associated with liver injury were identified. Population-adjusted exposure rates increased nearly 4-fold (10.9-52.9 per million). Women accounted for most exposures (54%). More than 80% of exposures required inpatient hospitalization, indicating substantial clinical severity. Medication-related exposures accounted for the majority of cases (men, 85%; women, 94%), with APAP-alone the most frequently implicated xenobiotic (men, 33%; women, 45%). APAP-containing combination products declined by approximately 60% to 85% following regulatory actions in the early 2010s, whereas APAP-alone exposures increased substantially (men, 349%; women, 380%). CONCLUSIONS:Clinically significant XILI has increased substantially over the past 25 years, with APAP-alone emerging as a growing and persistent contributor. These findings underscore the value of poison center surveillance for monitoring hepatotoxic risk and informing targeted prevention strategies in an era of expanding reliance on nonopioid analgesics.
