Clinical outcomes of potential coeliac disease: a systematic review and meta-analysis.

OBJECTIVE: Potential coeliac disease (PCD) is characterised by positive serological and genetic markers of coeliac disease with architecturally preserved duodenal mucosa. The clinical outcomes and rates of progression to overt coeliac disease in patients with PCD remain uncertain. In this systematic review and meta-analysis, we aimed to evaluate the clinical outcomes of patients with PCD. DESIGN: We searched Medline, Embase, Scopus and Cochrane Library from 1991 through May 2024 to identify studies evaluating the clinical outcomes of patients with PCD. The progression rates to villous atrophy, seroconversion and response to a gluten-free diet (GFD) were analysed. A random-effect meta-analysis was performed, and the results were reported as pooled proportions with 95% CIs. RESULTS: Seventeen studies comprising 1010 patients with PCD were included in the final analyses. The pooled prevalence of PCD among patients with suspected coeliac disease was 16% (95% CI 10% to 22%). The duration of follow-up in most of the studies was at least 1 year, with follow-up periods within individual studies ranging from 5 months to 13 years. During follow-up, 33% (95% CI 18% to 48%; I2=96.4%) of patients with PCD on a gluten-containing diet developed villous atrophy, and 33% (95% CI 17% to 48%; I2=93.0%) had normalisation of serology. Among those who adhered to a GFD, 88% (95% CI 79% to 97%; I2=93.2%) reported symptomatic improvement. CONCLUSION: Almost a third of patients with PCD develop villous atrophy over time, whereas a similar proportion experience normalisation of serology despite a gluten-containing diet. Most symptomatic patients benefit from a GFD. These findings highlight the importance of structured follow-up and individualised management for patients with PCD.

New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Distinguishing Features of Autoimmune Gastritis Depending on Previous Helicobacter pylori Infection or Positivity to Anti-Parietal Cell Antibodies: Results From the Autoimmune gastRitis Italian netwOrk Study grOup (ARIOSO).

INTRODUCTION: To describe the clinical features and the risk of developing gastric tumors in patients with autoimmune gastritis (AIG). METHODS: This was a retrospective, longitudinal, multicenter study conducted at 8 Italian tertiary referral centers. We retrieved clinical data from all histologically proven patients with AIG. Differences between Helicobacter pylori -exposed vs H. pylori -naive and anti-parietal cell antibody (PCA)-positive vs PCA-negative patients were investigated. The rate of gastric adenocarcinoma and type 1 gastric neuroendocrine neoplasm (gNEN) was assessed. A multivariable model for factors associated with gNEN was fitted. RESULTS: A total of 1,598 patients with AIG (median age 58 years, interquartile range 46-68; F:M ratio 2.7:1) were included. H. pylori -naive patients were more likely to have a first-degree family history of AIG (14.7% vs 8.9%; P = 0.012), type 1 diabetes mellitus (4.9% vs 2.3%; P = 0.025), and pernicious anemia (30.9% vs 21.1%; P = 0.003). PCA-positive patients had significantly more associated autoimmune diseases (59.0% vs 42.9%; P < 0.001) and were more likely to have been diagnosed by a case-finding strategy (15.3% vs 2.6%; P < 0.001). Overall, 15 cases (0.9%) of gastric adenocarcinoma and 153 cases (9.6%) of gNEN occurred, with a global rate of 0.12 (95% confidence interval [CI] 0.07-0.20) and 1.22 (95% CI 1.03-1.42) per 100 person/year, respectively. Having a vitamin B12/iron deficiency manifestation at AIG diagnosis was associated with a 16.44 (95% CI 9.94-27.20 P < 0.001) hazard ratio of gNEN. DISCUSSION: The "pure" AIG pattern has typical features of an autoimmune disease and seems to be unrelated to H. pylori . In a tertiary referral setting, the risk of developing overt gastric adenocarcinoma is low, while patients with vitamin B12 deficiency complications at onset may benefit from a more intense endoscopic follow-up for early gNEN detection.

Systematic review with meta-analysis: Cause-specific and all-cause mortality trends across different coeliac disease phenotypes.

BACKGROUND: Data on mortality in coeliac disease are contrasting. AIMS: To systematically review the literature on all-cause and cause-specific mortality in coeliac disease compared to the general population, and evaluate differences across clinical phenotypes, geographical regions, and over time. METHODS: We searched PubMed and Embase from 1 January 1970 to 31 December 2022 for eligible studies reporting on all-cause and cause-specific mortality in coeliac disease compared to the general population or controls. The protocol was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/852DN). RESULTS: We included 25 studies. All-cause mortality (HR 1.16, 95% CI 1.05-1.27, I2 = 89%), mortality due to malignancies (HR 1.21, 95% CI 1.08-1.36, I2 = 65%) and respiratory disease (HR 1.39, 95% CI 1.04-1.86, I2 = 76%) were increased. Mortality due to non-Hodgkin lymphoma (HR 10.14, 95% CI 2.19-46.88, I2 = 96%) was markedly increased. Mortality significantly decreased in recent decades: 1989-2004 (HR 1.61, 95% CI 1.27-2.03, I2 = 91%), 2005-2014 (HR 1.16, 95% CI 0.99-1.36, I2 = 89%), 2015-2022 (HR 1.19, 95% CI 1.05-1.35, I2 = 93%). All-cause mortality was not increased in dermatitis herpetiformis (HR 0.85, 95% CI 0.73-0.99, I2 = 40%) and undiagnosed coeliac disease (HR 1.09, 95% CI 0.95-1.25, I2 = 0%). Mortality was increased in the UK (HR 1.23, 95% CI 1.03-1.47, I2 = 91%) but not Scandinavia (HR 1.01, 95% CI 0.91-1.13, I2 = 81%). Limitations include high heterogeneity and lack of data for many countries. CONCLUSION: Mortality in coeliac disease is increased, predominantly due to malignancies-particularly non-Hodgkin lymphoma-although differing significantly across disease phenotypes. Mortality of patients with coeliac disease has significantly decreased in recent decades. These results may influence diagnosis and management.

Efficacy of a Low-FODMAP Diet for Coeliac Patients with Persistent IBS-like Symptoms despite a Gluten-Free Diet: A Systematic Review.

Background: Persistent symptoms in coeliac disease (CD) can be due to not only poor gluten-free diet (GFD) adherence and complications of CD, but also functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Although the role of a low fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet is well-established in IBS, little data are available on its role in coeliac patients with persistent IBS-like symptoms despite a GFD. Methods: We systematically reviewed the literature in accordance with the PRISMA guidelines for studies evaluating the role of FODMAPs and/or a low-FODMAP diet in coeliac patients with persistent symptoms. PubMed and Embase were searched from inception to 16 January 2024 for eligible full-text papers. The study protocol was registered on Open Science Framework. Results: A total of 239 records were identified, and six papers were included. Of these, four were interventional studies comparing a low-FODMAP GFD to a regular GFD for persistent symptoms in 115 total coeliac patients (two randomized controlled trials and two open-label studies). A low-FODMAP GFD for a minimum of 4 weeks was significantly more effective than a regular GFD in reducing symptoms (p < 0.05 in 3/4 studies). Dietary FODMAP content of a conventional GFD was significantly lower than that of non-coeliac patients on a gluten-containing diet (both p < 0.05), especially regarding high-FODMAP grain products. However, coeliac patients consumed more servings of fruits/vegetables high in FODMAP. No relationship between FODMAP intake and persistence of symptoms was reported. Conclusions: A low-FODMAP diet may be beneficial for uncomplicated celiac patients with persistent IBS-like symptoms despite strict adherence to a GFD.

Systematic review: Clinical phenotypes, histopathological features and prognosis of enteropathy due to angiotensin II receptor blockers.

BACKGROUND: Although enteropathy due to angiotensin II receptor blockers (ARBs) has been known for over 10 years, clinicians' awareness of this condition is still low. AIMS: To systematically review the literature about clinical phenotypes, distribution of mucosal changes throughout the gastrointestinal tract and prognosis of enteropathy due to ARBs. METHODS: According to PRISMA guidelines, we searched PubMed and Embase for relevant articles up to November 6, 2023. We included full-text papers, letters, case reports and case series describing enteropathy due to ARBs. Patients were classified into subgroups based on endoscopic and histological findings of different regions of the gastrointestinal tract. The protocol was registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/TK67C). RESULTS: We included 94 articles reporting 183 cases (101 female, mean age at diagnosis 69 ± 10 years). The clinical picture at diagnosis was characterised by severe diarrhoea (97%) and weight loss (84%, median -13 kg), leading to hospital admission in 167 (95%) patients. Olmesartan (90%) was most frequently implicated. Villous atrophy (VA) was reported in 164/183 (89%) patients. One hundred and nine had only VA, 12 had pan-gastrointestinal involvement, 23 had VA and gastric involvement and 19 had VA and colon involvement (predominantly microscopic colitis). Outcomes were reported for 178/183 (97%) patients, who all recovered clinically on ARBs withdrawal. Histological recovery occurred in all 96 patients with VA at baseline who underwent follow-up duodenal biopsy. CONCLUSIONS: Enteropathy due to ARBs is characterised by severe malabsorption often requiring hospital admission and can involve the entire gastrointestinal tract. Clinician awareness can lead to prompt diagnosis and excellent prognosis.

Comparison between SeHCAT test and clinical response to cholestyramine in patients with chronic diarrhea and high suspicion of bile acid malabsorption: A single-center prospective study.

OBJECTIVES: We aimed to evaluate the clinical response to cholestyramine in patients with functional chronic diarrhea and a high clinical suspicion of bile-acid diarrhea (BAD) investigated with 75-selenium homocholic acid taurine (SeHCAT) test. METHODS: Adult patients attending our outpatient clinic between January and December 2021 for chronic diarrhea with suspicion of BAD were proposed SeHCAT testing and a therapeutic trial of cholestyramine 4-8 g daily. Clinical response to cholestyramine was evaluated at 1, 3, 6, and 12 months. Clinical and demographic data were analyzed according to SeHCAT test results. RESULTS: Among the 50 patients with chronic diarrhea and clinical suspicion of BAD, 13 (26.0%) refused either SeHCAT testing or cholestyramine therapy. Finally, 37 patients (31 females, age 44 ± 14 years) agreed to undergo SeHCAT and were started on cholestyramine (median follow-up 14 months [interquartile range 6-16 months]). Initial response to cholestyramine was similar in patients with positive and negative SeHCAT test results, but improved over time in those with a positive test result. Long-term response (100% vs 65.2%, P = 0.02) and necessity of maintenance therapy for symptom control were more common in those with positive SeHCAT test result (71.4% vs 26.1%, P = 0.02). However, response to cholestyramine was also frequent in patients with a negative test result. CONCLUSIONS: The SeHCAT test accurately identifies patients with BAD who benefit from long-term cholestyramine treatment. Nevertheless, cholestyramine may be also effective in patients with chronic diarrhea but negative SeHCAT test result.

A small bowel adenocarcinoma harboring a DDR2 mutation in a celiac patient.

We present the case of a 62-year-old man with a history of celiac disease and IgA deficiency, following a strict gluten-free diet that was admitted to our hospital for recurrent abdominal pain, fatigue and melena. Esophagogastroduodenoscopy and colonoscopy with biopsies were normal. A video-capsule endoscopy was performed and revealed a sub-stenosing, vegetating, and bleeding lesion in the first jejunal loop. He underwent laparotomic surgery with resection of the involved segment with loco-regional lymphadenectomy. The pathological report described a poorly differentiated adenocarcinoma of the jejunum, stage IIIA (pT3pN1). Analysis of next-generation sequencing (NGS) of DNA on the surgical sample revealed a likely pathogenetic variant in exon 15 of the DDR2 gene (c.2003G > A) and a TP53 non-frame-shift deletion (c.585_602del). Considering the risk of recurrence, he was candidate to 6 months of adjuvant chemotherapy with platinum salt and fluoropyrimidine. Thirty-eight months after the diagnosis, the patient is still disease free and in good clinical condition. This is the first described case of SBA with DDR2 mutation. Considering the limited therapeutic options beyond surgery for SBA, molecular analyses could become promising for the search for potential targetable alterations for treatments with new available drugs.

Superior bowel preparation quality for colonoscopy with 1L-PEG compared to 2L-PEG and picosulphate: Data from a large real-world retrospective outpatient cohort.

BACKGROUND: Several randomized clinical trials comparing different bowel preparations (BP) have shown similar efficacy; however, there is a lack of real-world studies on this topic. AIMS: This study aims to identify the most effective BP regimen in a real-world setting and any predictors of inadequate BP. METHODS: A retrospective single-center study was conducted over 14 months at an academic hospital including outpatient colonoscopies in which adult patients did not teach on how to perform BP before colonoscopy. Colonoscopies with 1L-PEG, 2L-PEG and picosulphate mixtures were considered. A multivariable analysis for factors associated to poor BP was fitted. RESULTS: Overall, 1779 patients (51 %F, 60±14) years were included. The 1L-PEG regimen provided a higher rate of BP adequacy at multivariate analysis (adjusted OR 2.30, 95 %CI 1.67-3.16,p < 0.001) and was associated with higher median Boston Bowel Preparation Scale score (p < 0.001), higher rate of right-colon cleansing (p < 0.001) and exam completion (p = 0.04). Furthermore, we identified male sex, history of constipation, active smoking, previous pelvic surgery, concomitant psychiatric/neurological or chronic kidney diseases as predictors of inadequate BP. CONCLUSIONS: This is the largest real-world study comparing 1L-PEG to other BP regimens. Our results suggest 1L-PEG provides better BP in a non-controlled setting, improving clinical practice quality and minimizing the need for repeated colonoscopies and saving healthcare resources.