Aggarwal Nishant, Bhatia Unnati, Dwarakanathan Vignesh, Singh Achintya Dinesh, Singh Prashant, Ahuja Vineet, Makharia Govind K
Department of Internal Medicine, William Beaumont University Hospital, Royal Oak, Michigan, USA.
Department of Community Medicine, Employees' State Insurance Corporation Hospital, Chennai, India.
J Gastroenterol Hepatol. 2025 Jan;40(1):101-107. doi: 10.1111/jgh.16808. Epub 2024 Nov 18.
Non-responsive celiac disease (NRCD) is defined as ongoing symptoms despite 6-12 months of gluten-free diet (GFD), the only known treatment for celiac disease (CeD). There is inconsistency in studies describing the proportion of patients having NRCD and its various causes among patients with CeD. We therefore conducted a systematic review and meta-analysis to determine the prevalence and causes of NRCD.
The PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched for original studies reporting the proportion of patients with persistent symptoms after ≥ 6 months of GFD. Studies reporting the etiologies of NRCD were also identified. The systematic review was conducted as per the Meta-analysis of Observational Studies in Epidemiology guidelines. Statistical analysis was performed in STATA.
Of 2965 search results, nine studies met the inclusion and exclusion criteria. Five studies (n = 4414) reported data on prevalence, and seven studies (n = 790) reported the causes of NRCD. The pooled prevalence of NRCD was 22% (95% confidence interval, 11-35%). Among patients with NRCD, inadvertent exposure to gluten was the most common cause (33%), followed by functional gastrointestinal disorders including irritable bowel syndrome in 16%. Refractory CeD type II along with its premalignant and malignant sequelae was observed in 7% of patients with NRCD.
One in five patients with CeD may not respond to GFD and would likely be classified as NRCD. Inadvertent gluten exposure was the cause of ongoing symptoms in one-third of patients with NRCD. Improving adherence to GFD along with developing novel therapeutics to mitigate symptoms due to ongoing gluten exposure is critical.
难治性乳糜泻（NRCD）被定义为尽管接受了无麸质饮食（GFD）6 - 12个月（乳糜泻（CeD）唯一已知的治疗方法），症状仍持续存在。关于CeD患者中NRCD患者比例及其各种病因的研究存在不一致性。因此，我们进行了一项系统评价和荟萃分析，以确定NRCD的患病率和病因。
检索PubMed、Embase、Cochrane图书馆、Scopus和Web of Science数据库，查找报告GFD≥6个月后仍有持续症状患者比例的原始研究。还确定了报告NRCD病因的研究。根据流行病学观察性研究的荟萃分析指南进行系统评价。在STATA中进行统计分析。
在2965条检索结果中，9项研究符合纳入和排除标准。5项研究（n = 4414）报告了患病率数据，7项研究（n = 790）报告了NRCD的病因。NRCD的合并患病率为22%（95%置信区间，11 - 35%）。在NRCD患者中，意外接触麸质是最常见的原因（33%），其次是功能性胃肠疾病，包括肠易激综合征，占16%。7%的NRCD患者观察到II型难治性CeD及其癌前和恶性后遗症。
五分之一的CeD患者可能对GFD无反应，可能会被归类为NRCD。意外接触麸质是三分之一NRCD患者持续症状的原因。提高对GFD的依从性以及开发新的治疗方法以减轻因持续接触麸质而产生症状至关重要。
