Beyond biopsy: evaluating noninvasive techniques to diagnose celiac disease in adults

Duodenal biopsies are standard for diagnosing celiac disease (CD), but a biopsy-free approach has gained attention in the past decade. Evidence suggests that immunoglobulin A anti-tissue transglutaminase (IgA tTg) antibody levels ≥10 times the upper limit of normal (ULN) may reduce the need for histology. This study aimed to assess whether IgA tTg antibody titers ≥10 × ULN correlate with the histological diagnosis in adults.

The retrospective study was conducted at Mater Dei Hospital, Malta, analyzing adult patients who underwent upper gastrointestinal endoscopy with duodenal biopsies between 2012 and 2024. Data on demographics, symptoms, risk factors, serology and histological results were collected. Patients who had positive serology but initial negative biopsies and underwent repeat biopsies were also reviewed.

Of 114 patients (78.1% female, mean age 41.0 years), 97.4% tested positive for IgA tTg antibodies and 93.8% for endomysial antibodies (EMA). CD was histologically confirmed in 70.2%, with females more frequently diagnosed than males (75.3% vs. 52%, P=0.025). CD-related symptoms were reported by 79.8%, while 20.2% were asymptomatic. Levels of tTg ≥10 × ULN were found in 41.2% patients, and this cutoff had a sensitivity of 58.8%, specificity of 100%, positive predictive value of 100% and negative predictive value of 50.7% for CD (P<0.001).

This study supports a biopsy-free approach for diagnosing CD when IgA tTg levels are ≥10 x ULN, especially with EMA positivity and typical clinical presentation.