Nishant Aggarwal, MD1, Unnati Bhatia, MD1, Vignesh Dwarakanathan, MBBS, MD2, Prashant Singh, MD3, Govind Makharia, MBBS, MD, DM4 1William Beaumont Hospital-Royal Oak, Royal Oak, MI; 2ESIC Medical College and Hospital, Chennai, Tamil Nadu, India; 3University of Michigan, Ann Arbor, MI; 4All India Institute of Medical Sciences, Delhi, Delhi, India
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.
Discussion: One in five 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: Figure 1: Forest plot depicting the pooled prevalence of non-responsive celiac disease (NRCD) in our review.
Disclosures:
Nishant Aggarwal indicated no relevant financial relationships.
Unnati Bhatia indicated no relevant financial relationships.
Vignesh Dwarakanathan indicated no relevant financial relationships.
Prashant Singh indicated no relevant financial relationships.
Govind Makharia indicated no relevant financial relationships.
Nishant Aggarwal, MD1, Unnati Bhatia, MD1, Vignesh Dwarakanathan, MBBS, MD2, Prashant Singh, MD3, Govind Makharia, MBBS, MD, DM4. P4106 - Prevalence and Etiologies of Non-Responsive Celiac Disease: A Systematic Review and Meta-analysis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.