S1833 Prevalence and Etiologies of Non-responsive Celiac Disease: A Systematic Review and Meta-Analysis
Bibliographic record
Abstract
Introduction: Lifelong gluten free diet (GFD) is the only known treatment of celiac disease (CeD), but the response is variable and a significant proportion of patients may continue to experience clinical symptoms despite adherence to GFD. Non-responsive CeD (NRCD) is defined as lack of initial response to GFD in patients with CeD after 6-12 months of GFD, or recurrence of symptoms in a patient who initially responded to GFD despite continued dietary adherence. Recent studies have been inconsistent on the proportion of NRCD amongst patients with CeD. Therefore, we decided to conduct a systematic review and meta-analysis to determine the prevalence and causes of NRCD. Methods: We conducted a search of the PubMed, Embase and the Cochrane Library databases for original studies published in English reporting the proportion of patients with persistent symptoms after >6 months of GFD. Studies reporting the etiologies of NRCD were identified separately. The systematic review was conducted as per the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. Quality assessment was performed using the Newcastle Ottawa Scale. Statistical analysis was performed in STATA v14. Results: Of a total of 792 search results, after inclusion and exclusion criteria, 8 studies were included in the systematic review, of which 5 studies (n= 4,414) reported data on the prevalence of NRCD and 6 studies (n= 678) reported the causes of NRCD. Pooled prevalence of NRCD was 22% (95%CI, 11-35%, I2= 98.6%, Figure 1). Amongst patients with NRCD, inadvertent exposure to gluten was the most common cause (49% [95%CI, 36-63%, I2= 86.7%]), followed by functional gastrointestinal disorders including irritable bowel syndrome (21% [95%CI, 13-30%, I2= 81.7%]) and RCD1 (10% [95%CI, 0-33%, I2= 96.4%]). RCD2 along with its premalignant and malignant sequelae was noted in 8% (95%CI, 2-18%, I2= 90.4%) of patients with NRCD. Other causes of NRCD in this review were small intestinal bacterial overgrowth, microscopic colitis, disaccharide intolerance, and inflammatory bowel disease. Conclusion: One in 5 patients with CeD may not respond to GFD and would likely be classified as NRCD. Amongst many other causes, the commonest cause of NRCD was found to be inadvertent exposure to dietary gluten. In order to mitigate NRCD, patients with CeD should receive comprehensive counselling regarding GFD and a systematic approach should be followed for the appropriate evaluation for other causes of NRCD.Figure 1.: Forest plot depicting the pooled prevalence of non-responsive celiac disease (NRCD) in our review.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.015 | 0.038 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.018 | 0.043 |
| Bibliometrics | 0.010 | 0.010 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".