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.

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.

Fecal calprotectin measurement as a biomarker of severe disease phenotype in celiac disease and non-celiac enteropathies.

BACKGROUND: Fecal calprotectin (FC) is a non-invasive biomarker of gut inflammation, but its role in celiac disease (CD) and non-celiac enteropathies (NCEs) is undefined. AIMS: To retrospectively evaluate FC in patients with CD and NCEs as a tool for assessing disease activity and predicting long-term outcomes. METHODS: Patients with uncomplicated and complicated CD, and NCEs with data on FC, evaluated at our center between June-2008 and December-2023, were enrolled. The relationship between elevated FC (>50 mg/kg) and disease activity was statistically analysed and Cox regression adjusted for age and sex was used to compare development of complications and mortality in patients with elevated and normal FC. RESULTS: 177 patients (109F, mean age at diagnosis 39±20 years, 132 CD, 17 complicated CD, 28 NCEs) were enrolled. 55 patients had elevated FC, which was associated with lack of clinical and histological response to therapy (both p < 0.001). During a median follow-up of 103 months (IQR 54-176), 22 patients developed complications (15.4 %) and 21 died (11.9 %). Elevated FC was significantly more common in complicated CD (70.6 %) and NCEs (67.9 %) than in uncomplicated CD (18.2 %), p < 0.001. Elevated FC was independently predictive of developing complications (HR 4.8,95 %CI 1.4-17.7, p = 0.01) and mortality (HR 4.8,95 %CI 1.6-14.3, p < 0.01). CONCLUSION: FC is a promising non-invasive biomarker for assessing disease severity and long-term outcomes in CD and NCEs.