New Data Support No-Biopsy Approach for Celiac Disease Diagnosis

The definition of celiac disease as found in a medical dictionary.
Investigators assessed the predictive capacity and diagnostic yield of a minimum 10-fold increase in serum IgA antitissue transglutaminase antibody levels in celiac disease.

Study data published in Gut suggest that IgA antitissue transglutaminase (tTG) titres 10 or more times the upper limit of normal (ULN) are strongly associated with small intestinal mucosal changes diagnostic of celiac disease (CD). A 10-fold increase in tTG antibody levels in the presence of antiendomysial IgA antibodies (EMA) positivity may be “sufficient to make a diagnosis of CD,” potentially supporting a no-biopsy approach for the diagnosis of CD, according to the investigators.

The study included 1417 patients, 30% of whom were found to have elevated tTG titres (≥10×ULN). Of these 431 patients, 98% had Marsh 3 lesions on duodenal biopsy and were subsequently diagnosed with CD. Marsh 3 histology was used as the primary reference standard across the 3 cohorts.

Regarding the patient makeup of each group, cohort 1 included 740 patients assessed at a specialist CD clinic at a center in the United Kingdom (UK). The prevalence of CD among these patients was 93.0%. Cohort 2 encompassed 532 patients with low suspicion for CD for whom upper gastrointestinal endoscopy was recommended. Among patients in this group, who were seen at another UK center, the prevalence of CD was 3.2%. Finally, cohort 3 comprised 145 patients with raised tTG titres from multiple international sites. The prevalence of CD in this cohort was 92.0%.

Across the 3 cohorts, almost all adults with tTG tires of 10 times or more the ULN were found to have “small intestinal mucosal changes diagnostic of CD” on duodenal biopsy. The positive predictive value for IgA tTG levels 10 times the ULN or greater at identifying individuals with Marsh 3 lesions was 98.7%, 100.0%, and 95.2% in cohorts 1, 2, and 3, respectively. In line with existing data, the study authors “found that a tTG titre threshold of [10 times the ULN] accurately identified individuals with Marsh 3 lesions.”

The findings support a “no-biopsy strategy in adult gastroenterology services,” the study authors stated, adding that “local validation of assay-specific thresholds would enable this approach to have the greatest impact on adult patients.” Notably, the clinical insight aligns with the Paediatric European Society for the Study of Paediatric Gastroenterology, Hepatology, and Nutrition guideline suggestion that CD diagnoses can be made without taking duodenal biopsies.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of the authors’ disclosures.

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Penny HA, Raju SA, Lau MS, et al. Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts. Gut. Published online November 2, 2020. doi:10.1136/gutjnl-2020-320913