A blood test may be reliable in diagnosing some adults with suspected celiac disease, helping to avoid a biopsy, according to a prospective cohort study.
In 436 adults with suspected disease and without IgA deficiency, a serum anti-tissue transglutaminase IgA (tTG-IgA) test was compared with the gold standard: duodenal biopsy. The result was that the serum testing turned up 348 true positives and 66 true negatives, but also 15 false positives and seven false negatives, said researchers led by Carolina Ciacci, MD, of the University of Salerno in Italy.
Reporting online in Lancet Gastroenterology and Hepatology, Ciacci’s group said the positive predictive value of the blood test was 95.9% (95% CI 92-99.8) and the negative predictive value was 90.4% (95% CI 85.5-95.3). The sensitivity was 98% (95% CI 95.3-100) and the specificity was 81.5% (95% CI 73.9-89.1).
In a post-hoc analysis of adults whose tTG-IgA was more than 10 times the upper limit of normal, the serum test had a positive predictive value of 97.5% (95% CI 93.4-99.2), the researchers noted.
“With the use of tTG-IgA in patients with known concentrations of total serum IgA, a diagnosis will be established more quickly and treatment with a gluten-free diet started earlier than with biopsy,” Ciacci and colleagues wrote.
In addition, a non-biopsy approach reduces pressure on endoscopy clinics and reduces costs, according to the study authors. Another benefit for patients is avoiding an invasive, uncomfortable procedure that often requires sedation and sometimes a general anesthetic, they said.
Furthermore, although small bowel biopsy has been the gold standard for diagnosis, the histological interpretation is not always straightforward, which can lead to diagnostic delay or even misdiagnosis, they added.
Several clinical studies have shown the tTG-IgA test is feasible in children with suspected celiac disease, and this approach has been adopted by many healthcare systems and clinicians, mainly in Europe, the study authors said. However, the non-biopsy approach has not been widely adopted in adult practice.
A spokesperson for the American Gastroenterological Association who was not involved in the study, however, advised that diagnosis with biopsy should remain the standard for now.
“This study supports a growing evidence base that highly elevated tissue transglutaminase IgA levels mean that the patient is highly likely to have celiac disease,” said Benjamin Lebwohl, MD, a gastroenterologist at Columbia University Irving Medical Center in New York City, in an email to MedPage Today. “However, ‘highly likely’ is not 100%, and the gluten-free diet is a long-term treatment that entails a major life change, so getting as close to 100% as possible is important.”
“Because these antibodies remain imperfect,” Lebwohl continued, “I recommend that the intestinal biopsy remain the default for all adults with suspected celiac disease; in exceptional cases, where biopsy may be impractical or present safety concerns, these results can help us quantify the likelihood that an individual has celiac disease.”
Ciacci and colleagues conducted their study at 14 tertiary referral centers in Europe, Asia, Oceania, and South America. It included 296 women and 140 men with a mean age of 40. All had suspected celiac disease. None were on a gluten-free diet, and IgA deficiency was an exclusion criteria. They all underwent a serum tTG-IgA measurement and an endoscopic duodenal biopsy.
The serum test was defined as positive if it was more than one time the upper limit of normal. The main outcome was reliability of the tTG-IgA test to diagnose celiac disease, defined by duodenal villous atrophy as determined by a pathologist.
Participants were primarily from Europe, so the results cannot be extrapolated to the general population or other racial/ethnic groups, Ciacci’s group said. Another limitation was the relatively low number of individuals who did not have celiac disease as defined by duodenal villous atrophy.
“In conclusion, our results indicate that a serology-based celiac disease diagnosis without biopsy is possible in adults with reliable suspicion of celiac disease (high pretest probability),” they said.
No funding source was reported for this study. One author is an employee of Werfen. All others declared no competing interests.
The Lancet Gastroenterology & Hepatology
Source Reference: Ciacci C, et al “Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD): a multicentre, prospective cohort study” Lancet Gastroenterol Hepatol 2023; DOI: 10.1016/S2468-1253(23)00205-4.