What is the Optimal Method Assessing for Persistent Villous Atrophy in Adult Coeliac Disease?

Abstract

Background and Aims: Methods of assessing gluten-free diet (GFD) adherence in adults with coeliac disease (CD) include serological testing, dietitian evaluation, questionnaires and repeat duodenal biopsies. Persisting villous atrophy (VA) is associated with CD complications, however gastroscopy with biopsies is expensive and invasive. This study aimed to assess the abilities of a duodenal bulb (D1) biopsy and the Celiac Dietary Adherence Test (CDAT) to detect persisting VA in adults with CD.
 Methods: A prospective observational study of adult CD patients referred for follow-up duodenal biopsies was performed. Quadrantic biopsies were taken from the second part of the duodenum (D2), in addition to a D1 biopsy. Patients underwent follow-up serological testing, and completed the CDAT and Biagi Score. These non-invasive adherence markers were compared against duodenal histology.
 Results: 368 patients (mean age 51.0 years, 70.1% female) had D1 and D2 biopsies taken at follow-up gastroscopy. Compared to D2 biopsies alone, additional D1 biopsies increased detection of VA by 10.4% (p<0.0001). 201 patients (mean age 50.3 years, 67.7% female) completed adherence questionnaires and serology. When detecting VA, sensitivities and specificities of these markers were 39.7% and 94.2% for IgA- tTG, 38.1% and 96.4% for IgA-EMA, 55.6% and 52.2% for CDAT and 20.6% and 96.4% for the Biagi score.
 Conclusions: Bulbar biopsies increase detection of persisting VA by 10.4%. Serology, CDAT and Biagi performed poorly when predicting VA. The gold standard for predicting persisting VA remains repeat biopsy.

Biomarkers for the diagnosis and monitoring of celiac disease: can you count on me?

“…Therefore, all patients with suspected CeD should undergo oriented histological sampling, which should be randomly obtained in the duodenal bulb, and second and third duodenal segments. The duodenal bulb seems to be the most involved segment, according to a reported 10.4% increase in detection rate of villous atrophy when an additional duodenal bulb biopsy was taken [3].…”

Review article: Follow‐up of coeliac disease

“…19 The significance of enteropathy confined to the duodenal bulb is unknown. 26 We must sensitively communicate the goals of treatment to our patients, as those conscientiously avoiding gluten are understandably upset and frustrated by the finding of persistent enteropathy, and hypervigilance and fear of gluten exposure are associated with greater anxiety and depression. 27 Coeliac patients show highly variable mucosal healing rates on a GFD in follow-up studies ranging from 6 months to 10 years.…”

“…GFD adherence questionnaires are simple, rapid to administer and provide a quantitative readout of dietary adherence. However, both the 4‐item 69 and the 7‐item Celiac Dietary Adherence Test 70 questionnaires have poor sensitivity in detecting villous atrophy, of 25%–33% 43,71 and 55%, 26 respectively. While useful for clinical studies, the practical application of dietary questionnaires in the clinic appears limited.…”

“…It remains unclear if normal architecture with raised intraepithelial lymphocytes (Marsh 1) is similarly acceptable to complete mucosal normalisation as Marsh 1 changes have been linked to a modest mortality increase in coeliac disease 19 . The significance of enteropathy confined to the duodenal bulb is unknown 26 . We must sensitively communicate the goals of treatment to our patients, as those conscientiously avoiding gluten are understandably upset and frustrated by the finding of persistent enteropathy, and hypervigilance and fear of gluten exposure are associated with greater anxiety and depression 27 …”

“…However, the role of routine follow‐up biopsies, especially for patients with negative coeliac serology, replete nutritional markers and stable bone density, remains contentious. Surrogate markers of intestinal healing, such as normalisation of coeliac serology, are frequently used in the clinic and are simple, minimally invasive and preferred by patients, but they have poor predictive value for mucosal healing 9,26,35,51 . Non‐invasive molecular markers of mucosal healing have been assessed, for example intestinal fatty acid‐binding protein (I‐FABP), but lack sufficient utility to inform clinical practice 52 .…”