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

Abstract

Objective: Persistent villous atrophy (pVA) in coeliac disease (CD) despite a gluten-free diet (GFD) has unclear meaning. We aimed 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 multicentre retrospective-prospective study consisting of a study cohort (cohort 1) and an external validation cohort (cohort 2) of patients with biopsy-proven CD 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 (491F, 44±16 years). 157/694 (23%) had pVA. Risk of complications (HR 9.53, 95% CI 4.77 to 19.04, p<0.001) and mortality (HR 2.93, 95% CI 1.43 to 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 to 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 (OR 2.01, 95% CI 1.21 to 3.34, p<0.01), classical pattern of CD (OR 2.14, 95% CI 1.28 to 3.58, p<0.01), lack of clinical response to GFD (OR 2.40, 95% CI 1.43 to 4.01, p<0.001) and poor GFD adherence (OR 48.9, 95% CI 26.1 to 91.8, p<0.001).

Conclusions: Risk of complications and mortality were increased in patients with pVA. We developed a score to identify patients at risk of pVA and in need of histological reassessment and closer follow-up.

Keywords: celiac disease; epidemiology; gluten free diet; malabsorption.

Figure 1

Kaplan-Meier curves comparing complication-free survival in patients with persistent villous atrophy (VA) (continuous line) and with histological recovery (dotted line) on follow-up duodenal biopsy. Five-year complication-free survival was 84.3% in patients with persistent VA on follow-up duodenal biopsy and 99.4% in those with mucosal healing. Ten-year complication-free survival was 77.7% in patients with persistent VA on follow-up duodenal biopsy and 98.4% in those with mucosal healing.

Figure 2

Kaplan-Meier curves comparing overall survival in patients with persistent villous atrophy (VA) (continuous line) and with histological recovery (dotted line) on follow-up duodenal biopsy. Five-year overall survival was 97.3% in patients with persistent VA on follow-up duodenal biopsy and 99.4% in those with mucosal healing. Ten-year complication-free survival was 93.1% in patients with persistent VA on follow-up duodenal biopsy and 97.5% in those with mucosal healing.

Figure 3

A 5-point clinical score to stratify patients according to their risk of having persistent VA at follow-up duodenal biopsy. A score of ≥3 identifies patients at high risk of persistent VA. The score is calculated by summing the points obtained for each item. Dark grey: patients with persistent VA; light grey: patients with mucosal healing. GFD, gluten-free diet; ROC, receiver operating characteristic; VA, villous atrophy.