Background/Aims:Real-world evidence for upadacitinib use in strictly defined difficult-to-treat Crohn's disease (DTT-CD), particularly in Asian populations, remains limited. Herein, we aimed to evaluate the efficacy and safety of upadacitinib in Chinese patients with DTT-CD. Methods:This multicenter, bidirectional cohort study was conducted at 8 Chinese inflammatory bowel disease centers. Patients received upadacitinib 45 mg once daily for 12 weeks induction, followed by 15 mg daily for maintenance. The coprimary endpoints were clinical remission at week 12 and week 24. Results:Among the 151 DTT-CD patients enrolled, the clinical remission rates were 47.0% at week 12 and 62.9% at week 24, with endoscopic remission achieved in 28.1% of patients at week 24. Adverse events occurred in 42 (27.8%) during induction and in 33 (21.9%) during maintenance, with 3 serious events (venous thrombosis, perforation, and hemorrhage) reported during the maintenance phase. Notably, 2 male reproductive system-related adverse events were observed, including blue semen in 2 patients and a suspected case of paternal teratogenicity with fetal anomalies and pregnancy loss. The drug persistence at week 24 was 93.4%. Conclusions:Upadacitinib demonstrated robust efficacy in Chinese patients with DTT-CD, with a manageable safety profile and high treatment persistence.
Intestinal fibrosis is a debilitating complication of Crohn's disease that often leads to stricture formation, requiring surgical intervention. Despite its clinical significance, effective anti-fibrotic therapies remain an unmet need. Emerging evidence highlights the gut microbiome as a central orchestrator of fibrogenesis, beyond its role in inflammation. This review provides a comprehensive overview of how microbial dysbiosis, which is marked by the expansion of pathobionts such as adherent-invasive Escherichia coli and Clostridium innocuum, drives intestinal fibrosis through multifaceted pathways. We delineate the direct activation of fibroblasts via pattern recognition receptors and indirect mechanisms involving macrophage polarization, T helper 17 cell responses, and the emerging role of the "creeping fat" axis. Furthermore, we discuss how microbial translocation into the mesenteric adipose tissue triggers a profibrotic environment. By synthesizing these mechanistic insights, we suggest that targeting the microbiome-fibrosis axis, through precision modulation of the microbiome or metabolite-based interventions, represents a promising frontier for preventing and reversing fibrostenotic Crohn's disease.
Inflammatory bowel disease (IBD) is a chronic, relapsing, inflammatory condition of the gastrointestinal tract that primarily includes Crohn's disease and ulcerative colitis. Beyond the typical gastrointestinal symptoms, IBD is frequently associated with various extraintestinal manifestations (EIMs) affecting organs such as joints, skin, eyes, and the hepatobiliary system. As the prevalence of IBD rises in China, the identification and management of EIMs have become increasingly important. However, there is currently variation among Chinese physicians in their attention to, comprehensive assessment of, and management of EIMs in IBD. Therefore, this consensus aims to provide guidance for the systematic evaluation and multidisciplinary management of IBD-associated EIMs.
Venous thromboembolism (VTE) is a serious and potentially life-threatening complication in patients with inflammatory bowel disease (IBD), with the risk further increased during pregnancy and the postpartum period. Pregnancy induces a physiological hypercoagulable state, which, when combined with the chronic inflammatory and prothrombotic milieu of IBD, may result in synergistic thrombotic risk. Population-based cohort studies and meta-analyses consistently demonstrate an elevated risk of VTE during pregnancy and the postpartum period among women with IBD compared with those without, with risk being further amplified by active disease, hospitalization, or cesarean delivery. Current gastroenterology and obstetric guidelines recommend selective, risk-stratified thromboprophylaxis rather than routine anticoagulation for all pregnant women with IBD, emphasizing individualized assessment based on disease activity and additional obstetric risk factors. However, the majority of available evidence and current guideline recommendations are based predominantly on data from Western populations. Although the relative risk of VTE appears broadly comparable across ethnicities, Asian populations demonstrate substantially lower absolute incidence rates and distinct obstetric practice patterns, raising concerns regarding the direct applicability of Western guidelines. This narrative review summarizes the current evidence on the risk of VTE associated with pregnancy and the postpartum period in women with IBD and systematically examines existing thromboprophylaxis recommendations and safety considerations. Consequently, it identifies key clinical variables and analytical perspectives relevant to Asian populations that should be addressed in future research and aims to facilitate the development of population-specific, risk-based thromboprophylaxis strategies that balance the benefits and risks of anticoagulation.
Background/Aims:The exact cause of ulcerative colitis (UC) remains unclear but likely involves an immune response to an unidentified component of gut microbiota. The use of antibiotics in treating acute severe UC (ASUC) remains controversial. This study aimed to assess the benefits of adding antibiotics to corticosteroids for managing ASUC. Methods:This retrospective study included patients with ASUC who met the Truelove and Witts diagnostic criteria at admission and received intravenous (IV) corticosteroids, with or without adjunctive antibiotics. Key outcomes included the need for medical and surgical rescue therapy during hospitalization and UC-related re-hospitalization rates at 1 week, 3 months, and 1 year. Propensity score matching (PSM) was employed to minimize selection bias in evaluating the impact of adjunctive antibiotics on clinical outcomes. Results:Of the 386 screened patients, 222 met the inclusion criteria: 75 (33.8%) received IV corticosteroids alone, while 147 (66.2%) received IV corticosteroids combined with antibiotics. After PSM (60 patients per group), the addition of antibiotics showed no significant effect on the need for medical rescue therapy during hospitalization, re-hospitalization, or clinical response based on the partial Mayo score after 1 week of hospitalization (68.3% vs. 60.0%; P= 0.341). Similarly, no significant differences were observed in the need for medical rescue therapy, re-hospitalization, or UC-related surgery rates at 3 months or 1 year (P> 0.05). Conclusions:In patients with ASUC, treatment outcomes did not significantly differ between those receiving IV corticosteroids alone and those receiving a combination of IV corticosteroids and antibiotics, suggesting that adjunctive antibiotic use may offer no added clinical benefits.
Background/Aims: The risk of opportunistic infections (OIs) in inflammatory bowel disease (IBD) patients in Latin America is poorly known. We assessed the incidence and stratified the risk of OIs in IBD patients on immunosuppressive therapies. Methods: In this ambispective cohort study, we retrospectively analyzed the medical charts of IBD patients between March 2014 and March 2021 and prospectively analyzed those from April 2021 to April 2024. The incidence rate of OIs was expressed as the number per 1,000 patient-years (PY) and calculated for each treatment category. The risks of OIs associated with immunosuppressants were compared with exposure to aminosalicylates or no treatment using the Cox proportional hazards model. Results: In a total of 3,279.6 PY of follow-up, OIs occurred in 60 of 498 patients (12.0%) with an incidence rate of 18.3 per 1,000 PY. The most common OIs were herpes zoster (HZ; n = 28, 5.6%) and tuberculosis (n =17, 3.4%). The incidence rates of HZ and tuberculosis were 8.5 and 5.18 per 1,000 PY, respectively. Compared with patients on aminosalicylates or no treatment, the risk of OIs was higher in those on combination therapies with anti-tumor necrosis factor (TNF) and thiopurines (hazard ratio [HR], 7.67; 95% confidence interval [CI], 2.26-26.06), followed by thiopurine monotherapy (HR, 5.35; 95% CI, 1.56-18.3), and anti-TNF monotherapy (HR, 5.04; 95% CI, 1.50-16.97). Conclusions: IBD patients on long-term anti-TNF and/or thiopurine therapy had a higher risk of OIs, especially HZ and tuberculosis, compared with non-immunosuppressed patients. In the choice of therapies for IBD, the balance of individual drug effectiveness and safety is crucial. (Intest Res, Published online )
Background/Aims:The incidence of early-onset colorectal cancer is rising globally. While metabolic dysregulation is a known risk, the specific contribution of lipid profiles to colorectal carcinogenesis in young adults remains unclear. Remnant cholesterol (RC) has emerged as a significant cardiovascular risk factor, but its association with young-onset colorectal neoplasia is not fully elucidated. Methods:We conducted a retrospective, cross-sectional study of 4,100 asymptomatic individuals under 50 years of age undergoing screening colonoscopy. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. We used multivariate logistic regression to assess the independent association between RC levels and the presence of young-onset adenoma (YOA) and advanced YOA. Results:Patients with YOA had significantly higher RC levels than controls (17.65 ± 14.52 mg/dL vs. 14.69 ± 11.14 mg/dL; P< 0.001). In adjusted multivariate analysis, RC was independently associated with YOA risk (odds ratio [OR], 1.011; 95% confidence interval [CI], 1.003-1.019; P= 0.005). Notably, for advanced YOA, RC remained the only lipid parameter that retained statistical significance in the multivariable model (OR, 1.021; 95% CI, 1.004-1.038; P= 0.015), whereas traditional lipid markers were not significant. Conclusions:Higher RC levels were independently associated with YOA and advanced YOA in this cohort of asymptomatic individuals under 50 years of age. Among the lipid parameters examined, RC remained statistically significant in the multivariable model for advanced YOA.
Acute colonic diverticulitis is a common gastrointestinal inflammatory disorder. The incidence of acute colonic diverticulitis has been steadily increasing in Korea, particularly among younger and middle-aged adults. This rising prevalence, along with the observed differences in clinical characteristics compared to Western populations, underscores the need for region-specific, evidence-based guidance. The Korean Association for the Study of Intestinal Diseases (KASID) established a task force to develop these clinical practice guidelines to optimize the diagnosis and medical management of acute colonic diverticulitis tailored to the Korean healthcare environment. These guidelines were developed through a systematic literature review, critical appraisal of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, and expert consensus via a modified Delphi method. They addressed 12 clinical questions encompassing prognostic factors, diagnostic modalities, initial management for uncomplicated diverticulitis, management of complications, and prevention of recurrence. The resulting recommendations provide clinicians with evidence-based guidance for individualized management based on patients' condition and values. These guidelines aim to enhance the quality of care and optimize outcomes for patients with acute colonic diverticulitis in Korea.
Intestinal ultrasound (IUS) enables frequent, noninvasive assessment of inflammatory activity in ulcerative colitis and can support treat-to-target decisions without bowel preparation. Evidence from prospective cohorts indicates that early IUS changes within 1 to 2 weeks-particularly reductions in bowel wall thickness and color Doppler vascularity-are associated with shortterm response and can guide timely treatment optimization during induction. Follow-up assessments at 6 to 12 weeks further improve risk stratification by reassessing bowel wall thickness and Doppler vascularity, including composite indices such as the Milan Ultrasound Criteria, which correlate with endoscopic outcomes and subsequent medium- to long-term clinical events (e.g., relapse and colectomy). This review synthesizes the most reproducible IUS parameters and proposes a practical, time-windowed monitoring approach integrating IUS with symptoms, biomarkers, and endoscopy, whereby assessments within 1-2 weeks and again at 6-12 weeks provide actionable information to accelerate induction optimization and anticipate later outcomes in ulcerative colitis.
Background/Aims:To determine time to diagnosis (TTD) and its impact on surgery and advanced therapy (AT) burden in inflammatory bowel disease (IBD) in a multi-ethnic United Arab Emirates (UAE) cohort, a region in the acceleration phase of IBD incidence. Methods:Retrospective analysis of the UAE Epi-IBD registry. TTD was calculated from patient-reported symptom onset to diagnosis. Logistic, Poisson regression and Cox proportional hazards models were used. Sensitivity analyses using 6- and 18-month thresholds and TTD quartiles were performed. Results:Among 243 patients (148 Crohn's disease [CD], 95 ulcerative colitis [UC]), median TTD was 4.0 months (interquartile range [IQR], 1.5-9.0 months) for CD and 3.0 months (IQR, 1.0-7.0 months) for UC (P= 0.111, Wilcoxon; log-rank P= 0.054), shorter than pooled estimates from high-income countries. UC TTD accelerated significantly post-2021 (2.0 months vs. 5.5 months; P= 0.006), while CD remained stable (P= 0.646). Diagnostic speed was identical between tertiary and non-tertiary settings (P= 0.943). Diagnostic delay did not predict AT exposure (P= 0.986) or surgical risk (P= 0.586); instead, penetrating CD phenotype drove therapy burden (P= 0.019). Time to first AT was rapid (median 4.5 months for CD, 14.0 months for UC). Era-stratified analysis showed a trend toward higher AT use in 2021 to 2025 (incidence rate ratio, 1.36; 95% CI, 0.98-1.89; P= 0.071), consistent with expanding therapeutic availability, though null association between delay and outcomes persisted after adjustment. Conclusions:TTD in this cohort is shorter than global benchmarks and comparable to recent Asian data. Diagnostic delay did not predict adverse outcomes, though limited surgical events and short follow-up preclude definitive conclusions. Multiple factors beyond healthcare system architecture may contribute, and larger multicenter studies are needed.
Background/Aims:Combining therapies targeting distinct pathways shows promise in breaking the therapeutic ceiling for inflammatory bowel disease. The study explored real-world experiences and gaps between current evidence and clinical practice regarding advanced combined therapies. Methods:A cross-sectional online survey was conducted via QR code during meetings or email invitation. The survey covered participant demographics, experiences with advanced combined therapies for ulcerative colitis, Crohn's disease, and knowledge of these therapies. Results:Between March and October of 2024, 234 participants from 20 countries replied and 51.7% had adopted advanced combined therapies (86.0% had treated ulcerative colitis, 66.9% Crohn's disease, and 52.9% both). Among the 48.3% who had no experience, 76.1% would try if indicated. Refractory diseases were the most common indications. For combined therapies duration, 52.8% were time-oriented, favoring limited use within 6 months. Physicians reported no adverse events in 59.5% of cases. Of the events, infections (69.8%) were most common. Add-on strategy was the most commonly adopted, particularly the Janus kinase inhibitor added on anti-integrin for ulcerative colitis and anti-tumor necrosis factor alpha added on anti-interleukin 12/23 for Crohn's disease. Concomitant strategy followed, while sequential strategy was the least used. More non-Asian experts were experienced (82.4%) compared to Asian participants (46.5%). Both inexperienced and non-Asian physicians preferred add-on strategy, but prioritized goal-oriented use, targeting clinical and endoscopic remission. Conclusions:In real-world practice, advanced combined therapies were primarily used for refractory inflammatory bowel disease with limited duration. Add-on use was the most adopted. Differences in treatment approaches reflect varying levels of physician experience and geographical locations.
Background/Aims:This study aimed to investigate the prognostic value of early post-induction intestinal ultrasound (IUS) findings in predicting long-term clinical outcomes among patients with moderate-to-severe ulcerative colitis (UC). Methods:This retrospective, single-center study consecutively enrolled patients with moderate-to-severe, left-sided or extensive UC. Clinical endpoints were assessed at the end of follow-up or 1 year after induction therapy (for patients with at least 1 year of follow-up) and categorized as clinical remission (Short Clinical Colitis Activity Index [SCCAI] ≤ 2) or non-remission (SCCAI > 2). Patients who experienced a negative disease course before the evaluation point were classified as clinical non-remission. Results:A total of 56 patients were included. The bowel wall thickness (BWT; 5.1 ± 1.7 mm vs. 6.0 ±1.4 mm; P= 0.032) and Milan ultrasound criteria (MUC; 8.3 ± 3.2 vs. 9.9 ± 2.2; P= 0.029) evaluated at early follow-up IUS were lower for patients reaching longterm clinical remission. Patients with BWT < 5 mm on early follow-up IUS (83% vs. 45%; P= 0.006) or MUC < 6.2 (100% vs. 45%; P< 0.001) had a significantly higher rate of long-term clinical remission. Kaplan-Meier analysis revealed a lower cumulative probability of a negative disease course in patients with BWT < 5 mm (P= 0.025) or MUC < 6.2 (P= 0.025). Cox regression analysis identified BWT ≥ 5 mm as an independent predictor of a negative disease course. Conclusions:BWT <5 mm and MUC < 6.2 may serve as intermediate targets for IUS-guided "treat-to-target" strategy, offering a practical approach to improve longterm clinical remission in patients with moderate-to-severe UC.
Background/Aims:Previous evidence regarding the combined effects of metabolic disorders on intestinal barrier function (IBF) remains limited. We hypothesized that metabolic disorders interact to increase the risk of intestinal barrier dysfunction. Methods:This retrospective case-control study included 4,289 individuals who underwent IBF assessment. Controls with normal biomarker levels were propensity score-matched to cases with abnormal D-lactic acid, diamine oxidase (DAO), or endotoxin. Logistic regression and interaction models were applied to assess associations between metabolic indicators and intestinal barrier dysfunction. Results:Hypertension (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20-1.55; P< 0.001), dyslipidemia (OR, 1.70; 95% CI, 1.49-1.96; P< 0.001), and hyperglycemia (OR, 1.80; 95% CI, 1.57-2.08; P< 0.001) were significantly associated with intestinal barrier dysfunction. Subgroup analyses confirmed that dyslipidemia and hyperglycemia were independently associated with elevated DAO, D-lactic acid, and endotoxin levels. Both multiplicative and additive interactions were observed between key metabolic factors. Particularly, dyslipidemia and hyperglycemia showed significant additive interactions (relative excess risk due to interaction, 0.79 [95% CI, 0.19-1.35, P= 0.008]; attributable proportion due to interaction, 0.29 [95% CI, 0.06-0.46, P= 0.008]; synergy index, 1.82 [95% CI, 1.13-3.41, P= 0.008]). When stratified by age and sex, broadly similar trends were observed in participants aged ≥ 50 years and in males. Conclusions:Dyslipidemia and hyperglycemia are associated with intestinal barrier dysfunction and show a synergistic combined effect. Individuals with both should receive prioritized IBF monitoring and early metabolic intervention to protect barrier integrity.
