Esophagus to Small Intestine

Gut. 2023;72(11):2095–102

Schiepatti A, Maimaris S, Raju SA, Green OL, Mantica G, Therrien A, Flores-Marin D, Linden J, Fernández-Bañares F, Esteve M, Leffler D, Biagi F, Sanders DS

Persistent villous atrophy predicts development of complications and mortality in adult patients with celiac disease: A multicenter longitudinal cohort study and development of a score to identify high-risk patients

Objective: Persistent villous atrophy (pVA) in celiac disease despite a gluten-free diet (GFD) has unclear meaning. The aim of this study was to (i) study the relationship between pVA and long-term outcomes and (ii) develop a score to identify patients at risk of pVA.
Design: This is a multicenter retrospective-prospective study consisting of a study cohort (cohort 1) and an external validation cohort (cohort 2) of patients with biopsy-proven celiac disease diagnosed between 2000 and 2021. Cohort 1 was used to (i) compare long-term outcomes between patients with and without pVA (Marsh ≥ 3a) at follow-up biopsy and (ii) to develop a score to evaluate the risk of pVA, which was validated in cohort 2.
Results: Of 2211 patients, 694 (31%) underwent follow-up duodenal biopsy and were included in the study cohort (491 female, 44 ± 16 years). 157 of 694 (23%) had pVA. Risk of complications (hazard ratio [HR] = 9.53, 95% confidence interval [CI]: 4.77–19.04, p < 0.001) and mortality (HR = 2.93, 95% CI: 1.43–6.02, p < 0.01) were increased in patients with pVA. A 5-point score was developed and externally validated (receiver-operating characteristic area under the curve 0.78, 95% CI: 0.68–0.89) to stratify patients by risk of pVA: low (0–1 points, 5% pVA), intermediate (2 points, 16% pVA) and high (3–5 points, 73% pVA). Predictors for pVA used in the score were age at diagnosis ≥ 45 years (odds ratio [OR] = 2.01, 95% CI: 1.21–3.34, p < 0.01), classical pattern of celiac disease (OR = 2.14, 95% CI: 1.28–3.58, p < 0.01), lack of clinical response to GFD (OR = 2.40, 95% CI: 1.43–4.01, p < 0.001) and poor GFD adherence (OR = 48.9, 95% CI: 26.1–91.8, p < 0.001).

Conclusions: Risk of complications and mortality were increased in patients with persistent villous atrophy (pVA). A score was developed to identify patients at risk of pVA and in need of histological reassessment and closer follow-up.

Dr. A. Schiepatti, Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, IRCCS, Pavia, Italy, E-Mail:

DOI: 10.1136/gutjnl-2023-329751

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