Histological Recovery and Gluten-free Diet Adherence

A Prospective 1-year Follow-up Study of Adult Patients With Coeliac Disease

G. Galli; G. Esposito; E. Lahner; E. Pilozzi; V. D. Corleto; E. Di Giulio; M. A. Aloe Spiriti; B. Annibale


Aliment Pharmacol Ther. 2014;40(6):639-647. 

In This Article

Abstract and Introduction


Background Adequate gluten-free diet (GFD) is the only treatment for coeliac disease (CD). However, no agreement has been reached on either how and when to assess patient adherence to GFD or its effectiveness on villous atrophy.

Aim To assess, in a prospective study, patient adherence to and efficacy of GFD on histological recovery after 1-year of GFD.

Methods Between 2009 and 2012, we enrolled 65 consecutive newly-diagnosed adult patients (median age 38 years, 18–70) with biopsy-proven atrophic CD. Patients were re-evaluated after 1 year of GFD with duodenal histology, serological assays, symptoms and a dietary interview based on a validated questionnaire. Complete histological recovery was defined as the absence of villous atrophy and ≤30/100 intraepithelial lymphocytes.

Results Overall, 81.5% of patients had adequate adherence (ADA) to GFD, whereas 18.5% had an inadequate adherence (IADA); 66% of ADA patients and no IADA patients achieved complete histological recovery (P < 0.00001). Among ADA patients, antibody seroconversion and symptoms were not significantly different between patients who achieved complete histological recovery and those who achieved partial histological recovery with P = 0.309 and P = 0.197, respectively. Multivariate analysis showed that Marsh 3C was a risk factor for incomplete histological recovery in ADA patients (OR 8.74, 95% CI: 1.87–40.83).

Conclusions This study shows that complete histological recovery after 1-year of GFD in adult patients, who are assessed as adherent to the GFD, can be obtained in 66% of patients. Patients with severe histological damage at diagnosis are at risk for incomplete histological recovery 1 year later.


Coeliac disease (CD) is an immune-mediated disorder that affects approximately 1% of the Western population.[1,2] Patients with CD have intestinal lesions consisting of varying degrees of villous atrophy, crypt hyperplasia and intraepithelial lymphocytosis, as observed in duodenal biopsies.[3] The only known therapy is a lifelong gluten-free diet (GFD), which can lead to mucosal healing and improvements in symptoms and nutritional parameters. GFD may also prevent the onset of long-term complications, including malignancies.[4]

There is little evidence on the best method of assessing GFD adherence and mucosal healing during GFD. The evaluation of serum coeliac disease-associated antibodies, such as anti-transglutaminase and/or anti-endomysium (Ab tTG IgA and/or EMA), and the assessment of clinical symptoms are the most frequently used methods to assess CD patients during follow-up.[5–9] However, these antibodies often decrease and/or disappear regardless of histological healing and GFD adherence,[10–12] whereas the initial symptoms may improve right after the beginning of the GFD, even if the histological resolution is slower.[6,13,14] Therefore, antibody negativity and the disappearance of initial symptoms are not always reliable markers for assessing adherence and the histological response to diet. In adult patients on GFD, no agreement currently exists as to the necessity of gastroscopic/histological control during follow-up or regarding the appropriate timing.[15] In fact, the existing bodies of evidence contrast one another due to the retrospective nature of most relevant studies, which have used varying follow-up periods (ranging from 9 months to 33 years) and only sometimes adhered to validated methods of assessing GFD adherence.[11,16–20] Thus, few prospective studies have investigated intestinal histological recovery during GFD[12,21,22] using a validated tool for diet adherence.

The aim of this prospective study was to assess the adherence to and the efficacy of GFD on histological duodenal mucosa healing after 1 year of diet in newly diagnosed adult subjects.