American Journal of Gastroenterology最新文献

Background: Specific foods are associated with abdominal bloating, which can significantly impact quality of life.

Objective: To identify responders to fiber-induced bloating and the mechanisms underpinning clinical and microbial responses.

Design: Double-blind, placebo-controlled, randomized, 2-period, 2-challenge crossover trial in 41 individuals with functional bloating. Participants were randomized to 8 g/d of fructan or α-galacto-oligosaccharides (α-GOS) for 7 days with a 21-day washout. Clinical, nutritional, microbial (shotgun sequencing, metatranscriptomics) and fermentation (short-chain fatty acids, volatile organic compounds, breath hydrogen) profiles were characterized prior to each challenge to identify factors predicting response, and after the challenge to elucidate mechanisms underpinning food-induced bloating.

Results: Thirty-nine participants completed both challenges (39 fructan, 40 α-GOS). Overall, seven (7/39, 17.9%) participants were fructan responders and eight (8/40, 20%) were α-GOS responders (experienced fiber-related symptom induction). Clinical metrics indicative of bloating distinguished responders and non-responders to both challenges, including greater abdominal girth (fructan, p = 0.009; α-GOS, p = 0.030). α-GOS responders had higher breath hydrogen (H2) pre-challenge than α-GOS non-responders (p = 0.011). Trends were identified within metagenomic and metatranscriptomic gut microbial analyses, with higher carbohydrate active enzyme (CAZyme) diversity in fructan responders (pre-challenge, adjusted p-value (padj) = 0.024; post-challenge, padj = 0.042), and greater increase in gene expression for gamma-aminobutyric acid (GABA) degradation in α-GOS responders (padj = 0.041).

Conclusion: A higher burden of GI symptoms predicts clinical response to fermentable fibers in functional bloating, while for α-GOS, higher repeated fasting breath H2 is also a predictor. Gut microbiome function and fermentation is associated with functional bloating; however, further investigations are required to draw firm conclusions for the microbial influence in this interplay.ClinicalTrials.gov (Identifier: NCT04802798).

Introduction: The diagnostic Rome criteria, classify disorders of gut-brain interaction (DGBI) according to the anatomical region of the gastrointestinal (GI) tract from which the predominant symptom are perceived to originate. A study in Asian DGIB patients using an Enhanced Asian Rome questionnaire (EAR3Q) identified symptom clusters involving multiple anatomical section. Our aim was to investigate if DGBI symptom groupings involving more than one anatomical region can be found in both Eastern and Western DGBI patients. .

Methods: Physician-diagnosed DGBI patients, recruited from 5 Eastern and 6 Western, completed the EAR4Q. We performed an exploratory and confirmatory factor analysis on questionnaire data to identify symptom groupings, describing distinct DGBI diagnostic entities.

Results: 1074 DGBI patients (66.8% female, 42.6±14.6 years) were recruited. We identified 10 distinct symptom groupings; 1) irritable bowel syndrome predominant diarrhea (IBS-D) triggered by a meal and relieved by bowel movement or passing of flatus; 2) Constipation; 3) Upper GI symptoms with predominant regurgitation, nausea and vomiting; 4) Upper and lower GI symptoms relieved by bowel movement or flatus; 5) Epigastric pain or burning related to bowel movement or passing flatus; 6) Lower GI symptoms triggered or worsened by bowel movement or passing flatus; 7) Meal-related pain and gas symptoms; 8) Globus and dysphagia; 9) Functional chest pain and heartburn; 10) Constipation and belching relieved by bowel movement or passing flatus. While some symptom groupings aligned with the Rome IV diagnostics, several clearly include multiple anatomical regions, surpassing the scope of the Rome regional subdivision approach.

Conclusion: Our study revealed 10 distinct symptom clusters. Some aligned with Rome criteria but other extended beyond its strict anatomical divisions, challenging a key assumption of the Rome classification framework. These results provide novel insight on a multicontinental scale about the complexity of symptom patterns in DGBI and their anatomical relationships .

Introduction: Chronic pancreatitis strongly impairs patients' quality of life through pain and functional insufficiencies, which may be improved by implementing an evidence-based management algorithm. This study aimed to improve quality of life and reduce pain by increasing guideline adherence, using an evidence-based management algorithm, addressing exocrine and endocrine pancreatic insufficiency, nutritional status, bone health, pain management and lifestyle.

Methods: A nationwide stepped-wedge cluster-randomized controlled trial was performed across 26 Dutch centers collaborating in the Dutch Pancreatitis Study Group, representing six health-care regions. Current practice was compared to evidence-based management algorithm-guided care.Patients with a definite diagnosis of chronic pancreatitis, who were actively receiving care from a gastroenterologist or surgeon at the time of algorithm implementation were included during the current-practice phase and followed longitudinally. Co-primary endpoints were pain severity (Izbicki Pain Score) and quality of life (PANQOLI score), with a clinically relevant effect threshold defined as 10% of the maximum score, based on an expert consensus Delphi meeting. Analyses were performed according to intention-to-treat. Secondary outcomes included protocol adherence and several clinical outcomes. Total study duration was 35 months.

Results: Overall, 418 patients with chronic pancreatitis were included. Evidence-based management algorithm-guided care improved Izbicki Pain Scores (estimate: -1.72, 97.5% CI: -3.02 - -0.41, P < 0.001), without reaching the predefined threshold. No significant change in PANQOLI score was observed (estimate: 0.42, 97.5% CI: -0.44 - 1.27, p = 0.27). Median protocol adherence in patients who completed the follow-up period was 68.8% (IQR, 56.1 - 83.9). Stratified analyses by baseline scores and adherence did not yield clinically relevant improvements.

Conclusions: We found no superiority of an evidence-based management-algorithm over standard practice in improving quality of life or pain severity in all patients with chronic pancreatitis. However, by subgroup analyses, increased protocol adherence led to significantly better outcomes, especially in those with severe pain or low quality of life at baseline. These findings highlight both the complexity of, and the need for, dedicated protocol adherence in chronic pancreatitis management.

Trial registration: ISRCTN, ISRCTN13042622. Registered on 5 September 2020.

Background and aims: Despite the widespread use of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC), many patients remain at risk for progression. Emerging data suggest that normalization of alkaline phosphatase (ALP) and total bilirubin (TB) - particularly when TB <0.6 times the upper limit of normal (xULN) - is associated with improved outcomes compared to ALP reduction to <1.5 xULN. This study investigated the association between ALP normalization in response to UDCA and long-term clinical outcomes in a real-world cohort of patients with PBC.

Methods: We compared complication-free survival in patients achieving an ALP >ULN and <1.5 xULN (adequate response) to those with an ALP

Results: Patients achieving normal ALP and/or TB ≤0.6 xULN demonstrated significantly improved complication-free survival compared to those with an adequate ALP response. Event-free survival was extended by 1.34 years (95% CI:0.56, 2.11; p=0.001) for ALP normalization alone, 3.7 years (95% CI:3.11, 4.29; p< 0.001) for TB ≤ 0.6 xULN, and 4.51 years (95% CI:4.13, 4.88; p<0.001) for those meeting both criteria. The risk of severe clinical events was reduced in patients achieving ALP normalization (HR 0.34; 95% CI:0.15, 0.80; p=0.01), TB ≤ 0.6 × ULN (HR 0.23; 95% CI:0.09, 0.55; p=0.001), or both (HR 0.14; 95% CI:0.05, 0.38; p<0.001). High-risk patients, defined by LSM ≥10 kPa or clinical, histological, or laboratory evidence of cirrhosis or portal hypertension, derived the greatest benefit.

Conclusion: Achieving normal ALP and TB ≤0.6xULN is associated with significantly improved complication-free survival, particularly in high-risk patients. These findings highlight the potential of biochemical thresholds as a meaningful therapeutic goal in PBC management.

Introduction: Evaluate antibiotic patterns in the 12 months after an initial episode of pouchitis and associated factors.

Methods: In a population-based cohort, we identified the first episode of pouchitis (within 12 months of ileal pouch-anal anastomosis surgery) and used sequence analysis to identify antibiotic treatment patterns in the subsequent 12 months.

Results: Among 662 patients, we identified 4 clusters of antibiotic prescribing patterns, corresponding to patterns of intermittent and chronic pouchitis. Patients with chronic antibiotic-dependent pouchitis received antibiotics in most intervals after an initial episode of pouchitis.

Discussion: High-risk phenotypes after an initial episode of pouchitis suggest the need to evaluate the role of secondary prevention strategies.

Objectives: There are limited data on the safety of vedolizumab in pregnancy for the treatment of Crohn's disease or ulcerative colitis. Between 2015 and 2022, the Organization of Teratology Information Specialists conducted a prospective, observational pregnancy registry study with 275 pregnant women residing in the United States or Canada.

Methods: Women were enrolled in 1 of 3 cohorts: vedolizumab-exposed (N = 99); disease-matched unexposed to vedolizumab, but treated with another biologic in pregnancy (N = 76); or unexposed with no chronic health conditions (N = 100). Women and their infants were followed up to 1 year postpartum with maternal interviews, questionnaires, medical records abstraction, and a subset of infants who received a physical examination. Study outcomes were major structural birth defects, minor birth defects, pregnancy loss, preterm delivery, prenatal and postnatal growth deficiency, serious or opportunistic infections, malignancies, and developmental milestones.

Results: In the overall registry, 17 of 275 pregnancies (6.2%) were lost to follow-up. Among pregnancies ending in at least 1 live born infant, 7 of 94 (7.4%) in the vedolizumab-exposed cohort compared with 4 of 71 (5.6%) in the disease-matched cohort had a major birth defect (adjusted risk ratio 1.07, 95% confidence interval [CI] 0.33, 3.52). Compared with the disease-matched cohort, women in the vedolizumab-exposed group were not statistically significantly more likely to experience spontaneous abortion (adjusted hazard ratio 1.01, 95% CI 0.17, 5.89). Women in the vedolizumab-exposed group were slightly but not significantly more likely to deliver preterm (adjusted hazard ratio 1.58, 95% CI 0.65, 3.82).

Conclusions: No significant increased risks were noted with vedolizumab exposure for any of the other study outcomes. These data add reassuring evidence in support of the safety of vedolizumab in pregnancy.

Introduction: Anecdotal observations report a decrease in craving for alcohol among patients taking glucagon-like peptide-1 receptor agonists (GLP-1 RA). We aimed to assess liver-related outcomes and mortality among individuals with harmful alcohol use who received GLP-1 RAs.

Methods: We emulated a target trial using the electronic health records of US Veterans with positive alcohol use disorders-concise score (AUDIT-C), comparing new initiators of GLP-1 RA between 1/3/2017 and 9/30/2024, with controls, with follow-up until outcomes or study end. Each GLP-1 RA new user with a positive AUDIT-C screen was propensity score (PS) matched 1:1 with a patient not on a GLP-1 RA. The primary outcomes were the time to a composite outcome of decompensation, hepatocellular carcinoma, liver-related death, and all-cause mortality. The secondary outcome was the proportion of patients with positive AUDIT-C scores.

Results: We matched 8,040 patients with positive AUDIT-C initiated on GLP-1 RA with 8,040 noninitiators. GLP-1 RA use was associated with a lower risk of composite liver-related outcomes (adjusted hazard ratio [aHR], 0.70; 95% confidence interval [CI] 0.56-0.87) and death (aHR 0.43, 95% CI 0.37-0.49). Among semaglutide users, a 1 mg/wk dose increase was associated with a reduced risk of composite liver-related outcomes (aHR 0.50, 95% CI 0.29-0.88) and death (aHR 0.33, 95% CI 0.19-0.58). GLP-1 RA use was also associated with lower odds of positive AUDIT-C during follow-up (adjusted Odds ratio 0.75, 95% CI 0.68-0.82).

Discussion: In this observational target trial emulation study, GLP-1 RA use was associated with a lower risk of liver outcomes, death, and harmful alcohol use.