An IgA-tTG titer greater than 10 times the upper limit of normal has a very high positive predictive value.

Celiac disease currently is diagnosed using both serologic testing (evaluating IgA anti–tissue transglutaminase [IgA-tTG]) and duodenal biopsy. However, might a nonbiopsy approach, currently used in children, be suitable for diagnosing celiac disease in adults (NEJM JW Gen Med Jun 15 2021 and Gut 2021; 70:876)?

Investigators undertook a meta-analysis of 18 studies that involved 12,000 patients with suspected celiac disease and examined the accuracy of IgA-tTG levels ≥10 times the upper limit of normal (10× ULN) for predicting a positive duodenal biopsy for this disorder. Sensitivity of serology was 51% (i.e., IgA-tTG level was ≥10× ULN in about half of biopsy-proven cases). Specificity was >99% (i.e., almost no falsepositive serology results). Positive predictive value (PPV) was 98%, and negative predictive value (NPV) was 62%.

COMMENT
The prevalence of celiac disease in these studies was 62%, indicating a highly selected population and explaining the near-100% PPV when IgA-tTG is ≥10× ULN. None of the studies were done in primary care settings, where pretest probability would likely be much lower (and would depend on a clinician’s sense of who warrants testing). For example, if pretest probability were only 10%, the PPV of positive serology would still be high (≈95%) but probably not high enough to commit a patient to a lifelong gluten-free diet. In the end, primary care clinicians could discuss deferring biopsy in patients with high clinical probability of celiac disease and very high IgA-tTG levels. But a decision to omit biopsy should not necessarily mean no referral: Diagnosis and treatment ideally should involve both primary care and specialty care clinicians. — David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)

Dr. Bjorkman is Professor Emeritus in the Division of Gastroenterology, Hepatology, and Nutrition at the University of Utah School of Medicine.

Shiha MG et al. Accuracy of the no-biopsy approach for the diagnosis of celiac disease in adults: A systematic review and meta-analysis. Gastroenterology 2024 Apr; 166:620. (https://doi.org/10.1053/j.gastro.2023.12.023)

GKB-NON-2024-00278