Clinical and Translational Gastroenterology最新文献

Introduction: Pancreatitis-associated osteopathy is a clinically significant but mechanistically underexplored complication of pancreatic disease. We aimed to characterize stage-specific alterations in bone remodeling biomarkers across the spectrum of disease: recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP).

Methods: In a cross-sectional analysis of North American Pancreatitis Study 2 participants, we measured serum mechanistic (sclerostin, dickkopf-1, receptor activator of nuclear factor κβ ligand, and osteoprotegerin), hormonal (fibroblast growth factor 23, insulin, and leptin), and modulatory (osteopontin, oncostatin, and osteoactivin) markers in controls (n = 30), RAP (n = 40), and CP (n = 40) using a multiplex assay. Group differences were assessed with ANOVA, Fisher exact test, and Kruskal-Wallis; multivariable regression identified predictors of biomarker variation.

Results: Eight of 10 biomarkers differed significantly among groups. Sclerostin, dickkopf-1, receptor activator of nuclear factor κβ ligand, and osteoprotegerin were elevated in RAP and CP vs controls, with the highest values in CP. The RANKL/OPG ratio was greatest in CP. Fibroblast growth factor 23 was increased in RAP, while insulin was reduced in CP. Osteopontin and oncostatin were elevated in pancreatitis groups, with osteopontin increasing progressively from control to RAP to CP. Several bone biomarker patterns varied by sex, tobacco, and alcohol use. Stepwise regression identified several significant predictors.

Discussion: These findings represent the most comprehensive bone metabolism biomarker profiling in pancreatitis to date, revealing stage-specific dysregulation of bone remodeling. Findings suggest a shift toward increased bone resorption and impaired formation with disease progression. Larger longitudinal studies are needed for marker validation, to clarify mechanisms, and guide targeted interventions to reduce bone loss and fracture risk in this high-risk population.

Introduction: Functional dyspepsia (FD), a disorder of gut-brain interaction defined by Rome IV criteria, overlaps frequently with irritable bowel syndrome (IBS) and reflux symptoms. Overlapping gastrointestinal (GI) disorders are associated with more psychological comorbidities and decreased quality of life, but data on physiological parameters in overlapping syndromes are scarce. The aim of this study was to evaluate the impact of overlapping disorders and FD subtypes on psychological and GI symptoms, as well as relevant physiological outcomes.

Methods: In total, 202 patients with predominant Rome IV FD symptoms and overlapping IBS and/or reflux were pooled from 7 studies conducted at University Hospitals Leuven. GI and psychological symptoms, as well as GI-related quality of life were recorded. Physiological measurements included salivary cortisol, gastric emptying, systemic and duodenal immune activation, and duodenal permeability.

Results: GI (Patient Assessment of Upper GI Symptom Severity and Leuven Postprandial Distress Scale [ P < 0.0001]) and psychological (anxiety [ P = 0.0014], depression [ P = 0.0017] and extraintestinal somatic symptoms [ P < 0.0001]) were more pronounced in FD with overlapping disorders, whereas all physiological parameters were similar. Patients with epigastric pain syndrome reported a milder symptom pattern compared with other FD subtypes, with similar physiological alterations. Duodenal eosinophils were associated with anxiety in FD, independent of overlapping GI disorders or subtype ( P = 0.043).

Discussion: The common overlap between FD, IBS, and reflux is characterized by a high GI-specific, psychological, and somatic symptom burden. By contrast, key pathophysiological parameters were not different between FD with and without overlapping disorders or between FD subtypes. Central integration of multiple GI manifestations rather than more severely impaired peripheral alterations is more likely to explain the high symptom burden in overlapping disorders.

Introduction: Noncirrhotic portal hypertension (NCPH) refers to a diverse group of disorders that affects the hepatic portosinusoidal vascular system resulting in portal hypertension (PH). Unlike cirrhosis, there are no noninvasive criteria to diagnose PH and varices in NCPH.

Methods: A prospective cohort of patients with NCPH who had transjugular liver biopsy, liver stiffness (LSM) measured using transient elastography, and laboratory and imaging data were included. PH was defined by the presence of one among the following-varices on endoscopy, portosystemic collaterals, or ascites on imaging. Logistic regression was used to identify predictors. The classification tree approach was used to identify cutoff values for the stepwise decision model.

Results: Of the 59 patients, 41 (69%) had PH and 36 (62%) had varices. LSM was higher in patients with PH (11.5 kPa vs 5.7 kPa, P < 0.01) and varices (12 kPa vs 5.9 kPa, P < 0.01). Platelet count was lower in patients with PH (79 vs 218 × 109/L, P < 0.01) and varices (75 vs 209 × 109/L, P < 0.01). Multivariate analysis combining LSM and platelet count predicts PH (area under receiver operating characteristic 96% [91%-99%]) and varices (area under receiver operating characteristic 92% [85%-99%]). A stepwise model combining platelet 140 × 109/L and LSM 7 kPa performed with a sensitivity of 100%, negative predictive value of 100%, and accuracy of 90% to detect PH. The same model performed with sensitivity of 100%, negative predictive value of 100%, and accuracy of 81% to detect varices.

Discussion: Noninvasive model combining LSM with platelet count can aid in identifying NCPH patients with PH and varices. However, this model requires validation in an independent cohort.

Introduction: Severe hepatic steatosis (HS) and significant hepatic fibrosis indicate severity of metabolic dysfunction-associated steatotic liver disease (MASLD), and the models for early detection are important. Recent studies suggest immunoglobulin G (IgG) glycosylation and microbial consortia may involve in the development of MASLD. This study investigates the utility of IgG glycosylation and microbial consortia in early detection models.

Methods: A total of 111 patients with MASLD categorized into high vs low controlled attenuation parameter (for HS) or high vs low FIB-4 (for fibrosis). We analyzed differences in microbial consortia and IgG1/IgG2 glycosylation features, creating scores for identifying severe HS and significant hepatic fibrosis. The combination scores for identifying severe HS and significant hepatic fibrosis in MASLD patients were derived based on the microbial consortia and IgG1/IgG2 glycosylation features accordingly.

Results: Megamonas was linked to severe HS, and Christensenellaceae R-7 , UCG-005 , CAG-56 , and Lachnospira were associated with significant hepatic fibrosis in patients with MASLD. The areas under curve of severe HS- and significant hepatic fibrosis-microbial scores were 0.731 and 0.773, respectively. The ratios of IgG2-N4H5F1/IgG1-N4H5F1 and bisected-IgG2/bisected-IgG1 predicted severe HS, while IgG2-N4H3F1/IgG1-N4H3F1, bisected-IgG1/bisected-IgG2, and IgG1-galactosylation/IgG2-galactosylation index identified significant hepatic fibrosis in MASLD. The combination scores including microbial consortia and glycosylation features achieved areas under curve of 0.776 and 0.810, showing comparable performance with established indices like HS index and FibroAST score.

Discussion: The study highlights the effectiveness of combining fecal microbiota and serum IgG glycosylation features in identifying MASLD severity, which are noninferior to the current regularly used models, and suggests the intervention of glycosylation as a promising therapeutic approach for MASLD.

Introduction: Gastrointestinal graft-versus-host disease (GI-GVHD) is a serious complication of hematopoietic stem cell transplantation, with diagnosis reliant on results of endoscopic biopsy. Optimal endoscopic approaches based on symptoms remain unclear.

Methods: We conducted a retrospective cohort study of 75 adult hematopoietic stem cell transplantation recipients with GVHD and GI symptoms undergoing endoscopic biopsy at Montefiore Medical Center (2015-2023). We assessed correlations between presenting upper (UGI) or lower GI (LGI) symptoms and biopsy-proven GVHD. Statistical analyses included χ 2 tests, phi coefficients, and logistic regression adjusting for demographic confounders. A subgroup analysis compared the diagnostic yield of flexible sigmoidoscopy vs full colonoscopy.

Results: Biopsy positivity strongly correlated with symptom location: 89.5% of patients with UGI symptoms had positive upper GI biopsies, and 100% with LGI symptoms had positive lower GI biopsies. χ 2 tests showed significant associations between symptoms and biopsy positivity ( P < 0.001), with phi coefficients indicating strong correlations ( r = 0.79 UGI; r = 0.82 LGI). Logistic regression confirmed symptom location as an independent predictor of biopsy results. Among 37 patients undergoing full colonoscopy, rectosigmoid biopsies showed perfect correlation with a diagnosis of GVHD ( r = 1.0, P < 0.001) when compared with other anatomic colon biopsy sites, suggesting flexible sigmoidoscopy is a cost-effective alternative for LGI symptoms.

Discussion: Symptom-guided endoscopic evaluation in GI-GVHD yields high diagnostic accuracy. Flexible sigmoidoscopy with targeted biopsies should be considered for patients with LGI symptoms because it may reduce procedural burden and health care costs without compromising diagnostic yield. These findings support symptom-directed, anatomically targeted approaches to improve patient care and resource utilization.

Introduction: We aimed to map the distribution of patients with inflammatory bowel disease (IBD) and gastroenterologists throughout the United States and identify local-level and state-level variations in the availability of specialist care.

Methods: For each first 3-digit ZIP code tabulation area (ZCTA) and state in the United States, we calculated the density of patients with IBD (Crohn's disease or ulcerative colitis) per 100,000 population, gastroenterologists per 100,000 population, and gastroenterologists per 100 patients with IBD. We used 2022 claims data to identify patients with IBD, the 2022 National Provider Identifier registry for provider details, and the 2020 US Census for area-level variables.

Results: Overall, 520,020 patients with IBD and 21,611 gastroenterologists were identified. Patient density varied across states, from 58.2 (New Mexico) to 337.1 (Maine). On average, there were 4.2 (ranging from 1.4 in Kansas to 9.8 in Hawaii) gastroenterologists/100 patients with IBD. The Midwest and the Southwest Border regions had the lowest density of gastroenterologists. Across the United States, 130 3-digit ZIP code tabulation areas (ZCTA) had zero gastroenterologists/100 patients; 62% of these ZIP codes were in rural areas, and 25% had household income <150% of the poverty line. ZIP codes with ≥5 gastroenterologists/100,000 population tended to have lower poverty rates and were more urban than those with 1 to <5 gastroenterologists/100,000 population.

Discussion: Geographic disparities in the availability of gastroenterologist care exist at the state and local levels. This disparity was highlighted for patients with IBD and populations living in rural and high-poverty areas.

Introduction: Evidence on the comparative real-world effectiveness of terlipressin vs midodrine plus octreotide (MO) for hepatorenal syndrome-acute kidney injury (HRS-AKI) in the United Kingdom and the United States is limited.

Methods: Using individual-level chart review data for patients across the United Kingdom (2013-2017) and the United States (2016-2019), an indirect treatment comparison was conducted comparing the efficacy of terlipressin (UK cohort) with MO (US cohort). Covariate balancing propensity scoring matched the cohorts on baseline serum creatinine (SCr), presence of encephalopathy and/or ascites, albumin use and duration, age, and sex. The primary endpoint was HRS reversal, defined as achieving SCr ≤1.5 mg/dL by the last day of treatment.

Results: At treatment initiation, 90.2% of UK patients received terlipressin (194/215), while 89.2% of US patients received MO (140/157). Concomitant albumin was administered in 67.9% of UK and 98.7% of US patients. In a covariate balancing propensity score-adjusted cohort, HRS reversal was achieved in 53.2% of terlipressin-treated patients (the United Kingdom, weighted effective sample size of 75) compared with 16.9% of MO-treated patients (the United States, n = 89) (adjusted mean difference (95% CI) 36.3% (22.4, 50.2), P < 0.0001). In adjusted analysis, individuals treated with terlipressin experienced an overall reduction in SCr at completion of treatment (SCr decrease 1.00 mg/dL vs increase of 0.08 mg/dL for MO-treated patients, P < 0.0001).

Discussion: HRS-AKI treatment and outcomes differ between the United Kingdom and the United States, attributed to the historical standard of care MO in the United States. In adjusted analyses, real-world use of terlipressin was more effective than MO at improving kidney function and achieving HRS-AKI reversal.

Introduction: Despite the growing recognition of autoimmune hepatitis (AIH)-metabolic dysfunction-associated steatotic liver disease (MASLD) overlap, studies today are limited by small sample sizes. The aim of this study was to investigate the impact of MASLD on the outcomes of patients with AIH using large-scale real world data.

Methods: This cohort study used the TriNetX research network to identify US adults (≥18 years) with AIH. Patients were stratified into those with MASLD (AIH-MASLD cohort) and controls (AIH without MASLD). Propensity score matching (1:1) between AIH-MASLD and controls accounted for demographics, comorbidities, and treatments. Outcomes were classified as short-term (within 1 year after diagnosis) or long-term (within 10 years) outcomes.

Results: Among 4,798 records with AIH, 1,440 AIH-MASLD patients were propensity matched with 1,440 controls. AIH-MASLD patients demonstrated reduced 1-year risks of all-cause mortality (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.44-0.98) and immunosuppressive medication use (HR 0.69, 95% CI 0.63-0.76), along with increased 10-year risks of cirrhosis (HR 1.22, 95% CI 1.06-1.40) and hepatocellular carcinoma (HR 2.03, 95% CI 1.09-3.78) compared with controls.

Discussion: In summary, our study using real-world evidence showed a significant association between MASLD and worse clinical outcomes in patients with AIH. Future efforts should be targeted toward facilitating early detection and management of MASLD in patients with AIH.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly used for managing diabetes and obesity. Although they improve glycemic control, they also delay gastrointestinal motility, potentially leading to inadequate bowel preparation for colonoscopy, which can increase the risk of missed lesions. This study aimed to evaluate the impact of GLP-1RA use on the quality of bowel preparation and on adenomas and sessile serrated polyp (SSP) detection.

Methods: We conducted a retrospective cohort study of outpatient screening and surveillance colonoscopies at a tertiary academic medical center. Adults who used a GLP-1RA within 1 week of their colonoscopy formed the treatment group; patients not on GLP-1RA (nonusers) who never used GLP-1RA served as controls. Propensity score weighting was applied for age, sex, BMI, race, diabetes status, and relevant medications. The subgroup analysis was stratified based on diabetes status and GLP-1RA use.

Results: Among 49,987 patients (4,269 GLP-1RA users, 45,718 nonusers), GLP-1RA use was associated with increased odds of inadequate bowel preparation (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.04-1.46). No significant difference in SSP and adenoma detection was observed. In subgroup analysis, GLP-1RA users with diabetes had the highest odds of inadequate preparation (OR 1.88, 95% CI 1.59-2.24) and the lowest odds of SSP detection (OR 0.71, 95% CI 0.57-0.89).

Discussion: GLP-1RA use, particularly among patients with diabetes, is associated with higher odds of inadequate bowel preparation and lower SSP detection, whereas adenoma detection was unaffected. Tailored bowel-prep protocols for GLP-1RA users with diabetes should be evaluated prospectively.