Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Current international guidelines recommend duodenal biopsies to confirm the diagnosis of celiac disease in adult patients. However, growing evidence suggests that immunoglobulin A (IgA) anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict celiac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of celiac disease in adults. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected celiac disease. We used a bivariate random effects model to calculate the summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value of the no-biopsy approach across different pretest probabilities of celiac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812. RESULTS: A total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven celiac disease in the included studies was 62% (95% confidence interval [CI], 40%-83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24%-40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42%-60%), and the summary specificity was 100% (95% CI, 98%-100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 - 0.89). The positive predictive value of the no-biopsy approach to identify patients with celiac disease was 65%, 88%, 95%, and 99% if celiac disease prevalence was 1%, 4%, 10%, and 40%, respectively. Between-study heterogeneity was moderate (I2 =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only 1 study had a low risk of bias across all domains. CONCLUSION: The results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pretest probability of celiac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.

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.

Idiopathic terminal ileitis: myth or true entity?

PURPOSE OF REVIEW: Isolated terminal ileitis is an increasing phenomenon identified during colonoscopy. Idiopathic terminal ileitis (IDTI) is a diagnosis of exclusion, representing a significant challenge from a diagnostic and management point of view. This review provides an overview of the most recent and relevant evidence on idiopathic IDTI, focusing on its evolution, the natural history and the management strategies proposed in the literature. RECENT FINDINGS: IDTI is uncommon, with a reported prevalence between 0.5 and 7%. The main differential is with Crohn's disease and intestinal tuberculosis in endemic countries. A proportion of patients (0-50%) can progress and develop Crohn's disease; however, there are no reliable predictive factors to stratify IDTI patients. SUMMARY: IDTI is a challenging entity, with a small proportion of patients progressing to Crohn's disease over time thus requiring follow-up. Noninvasive modalities such as capsule endoscopy are useful for follow-up, but further research is required to better understand this entity.

Clinical utility of the fracture risk assessment tool (FRAX) in biopsy-confirmed coeliac disease.

BACKGROUND: People with coeliac disease (CD) are at increased risk of osteoporosis and fractures. Currently, baseline dual-energy X-ray absorptiometry (DXA) is recommended for all patients with newly diagnosed CD. We aimed to determine the prevalence of osteoporosis and the clinical utility of the Fracture Risk Assessment Tool (FRAX) in predicting major osteoporotic fractures (MOF) in patients with biopsy-proven CD. METHODS: We retrospectively collected data for consecutive adult patients with biopsy-proven CD between 2001 and 2015 who underwent DXA scanning within 1 year of diagnosis and were followed up for a minimum of 7 years. Fracture risk was assessed using FRAX scores, and the incidence of major osteoporotic fractures during the follow-up period was analysed. RESULTS: A total of 593 patients (median age 45.0 years, 68.5% female) were included. The prevalence of osteopenia and osteoporosis were 32.3% and 14.5%, respectively. Increasing age (OR 1.06, p < .0001), decreasing BMI (OR 0.90, p = .003), and higher baseline immunoglobulin A-tissue tissue transglutaminase titre (OR 1.04, p = .03) were significantly associated with increased risk of osteoporosis. The sensitivity, specificity, positive and negative predictive values of the FRAX tool to predict MOF were 21.2%, 91.3%, 16.3%, 93.5%, respectively. A higher risk of fractures was associated with ongoing gluten exposure (OR 1.86, p = .02), previous fractures (OR 2.69, p = .005), and older age (OR 1.03, p < .0001). CONCLUSION: Osteoporosis is a common finding in patients with CD. The FRAX tool showed high specificity in predicting osteoporotic fractures and could be used to aid with patient selection for DXA scanning in some cases.

Cost-benefits and environmental impact of the no-biopsy approach for the diagnosis of coeliac disease in adults.

Objective: Recent evidence suggests that adult patients with IgA tissue transglutaminase levels of ≥10× the upper limit of normal could be accurately diagnosed with coeliac disease without undergoing endoscopy and biopsy. We aimed to evaluate the cost-benefits and the environmental impact of implementing the no-biopsy approach for diagnosing coeliac disease in clinical practice. Design: We calculated the overall direct and indirect costs of the conventional serology-biopsy approach and the no-biopsy approach for the diagnosis of coeliac disease based on the national average unit costs and the Office of National Statistics data. We further estimated the environmental impact of avoiding endoscopy based on the estimated greenhouse gas emissions from endoscopy. Results: Approximately 3000 endoscopies for suspected coeliac disease could be avoided each year in the UK. Implementing the no-biopsy approach for the diagnosis of coeliac disease in adults could save the National Health Service over £2.5 million in direct and indirect costs per annum and reduce endoscopy carbon footprint by 87 tonnes of CO2 per year, equivalent to greenhouse gas emissions from driving 222 875 miles, carbon emissions from charging over 10 million smartphones and the carbon sequestrated by 1438 trees grown for 10 years. Conclusion: The implementation of this non-invasive green approach could be an essential first step in the 'Reduce' strategy advocated by the British Society of Gastroenterology and other international endoscopy societies for sustainable endoscopy practice.

Incomplete small bowel capsule endoscopy: Risk factors and cost-effectiveness of real-time viewing.

Background and study aims International guidelines recommend real-time viewing (RTV) in capsule endoscopy for gastric emptying monitoring, yet it is often overlooked in clinical practice. We aimed to assess risk factors for incomplete small bowel capsule endoscopy (SBCE) and evaluate the clinical relevance and cost-effectiveness of RTV implementation. Methods We included consecutive SBCEs from 2013 to 2020. RTV was not applied per local protocol. We used multivariate logistic regression to identify risk factors for incomplete SBCE, including prolonged gastric transit time (GTT) and prolonged small bowel transit time (SBTT). Results Analyzing 858 SBCEs, we observed a completion rate of 94.6%. Prolonged GTT and SBTT were present in 4.9% and 18.2% of complete SBCEs, and in 13% ( P =0.03) and 10.8% ( P =0.24) of incomplete SBCEs, respectively. Only 0.7% (6 of 858) had incomplete SBCE with prolonged GTT. In both univariate and multivariate analysis, a modifiable (prolonged GTT odds ratio [OR] 2.9; 95% confidence interval [CI] 1.1-7.5) and two unmodifiable risk factors (inpatient status OR 2.3; 95% CI 1.1-4.5) and history of incomplete SBCE (OR 4.2; 95% CI 1.3-13.7) were independently linked to higher incomplete SBCE rates. The pretest completion probability was 90.5% and 95.8% in patients with and without unmodifiable risk factors, respectively ( P <0.01). The direct cost of systematic RTV adoption and prokinetics administration would be €5059, aiming to identify and treat each case of prolonged GTT associated with incomplete SBCE. Conclusions Modern devices make incomplete SBCE rare, usually not tied to prolonged GTT. In a low-incidence scenario, widespread RTV use brings high costs and uncertain effectiveness.

Role of capsule endoscopy and double-balloon enteroscopy in the management of adult patients with coeliac disease and persisting symptoms.

BACKGROUND: Small bowel capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are recommended for the management of patients with nonresponsive or refractory coeliac disease (CD). However, there is a paucity of data regarding the clinical profiles and outcomes of patients undergoing these investigations. METHODS: We conducted a retrospective analysis of two databases of adult patients with CD who underwent CE and/or DBE between 2017 and 2022 at the National Centre for Refractory CD in England. Patient demographic, clinical and endoscopic data were collected, and clinically relevant outcomes were reported. RESULTS: A total of 132 patients (median age 53 years, 64.4 % female) underwent 146 CEs and 25 DBEs. The most common symptoms were diarrhoea (51.5 %), abdominal pain (37.8 %), bloating (34.8 %), and weight loss (29.5 %). The overall detection rate of CE and DBE was 87.6 % and 92 %, respectively. Following CE and DBE, 14 patients (10.6 %) were diagnosed with CD-related complications such as ulcerative jejunitis, strictures and malignancy. Seven patients (5.3 %) died during follow-up, with five of these deaths directly attributed to CD. Older age, weight loss and anaemia were associated with poor outcomes. CONCLUSIONS: The sequential approach of CE and DBE identified CD-related complications in almost 1 in 10 patients with nonresponsive or refractory CD. Older patients with persistent villous atrophy, weight loss and anaemia require close monitoring to help with the early diagnosis and management of complications.