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

ObjectivePersistent 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.DesignThis 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.ResultsOf 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).ConclusionsRisk 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.

Systematic review with meta‐analysis: Cause‐specific and all‐cause mortality trends across different coeliac disease phenotypes

“…Among the included studies only one evaluated the relationship between mucosal healing and mortality, finding an inverse relationship, but this was not confirmed at multivariate analysis. 16 This is partly in contrast with the results of a recent multicentre study showing significantly increased mortality in patients with persistent atrophy 52 as well as prior evidence suggesting increased mortality in patients with persistent atrophy. 53 Several studies reported higher mortality in the first years after diagnosis, with a subsequent reduction in risk.…”

Cutaneous Disorders Masking Celiac Disease: Case Report and Mini Review with Proposal for a Practical Clinical Approach

“…Although Marsh–Oberhuber II lesions cannot be classified as CD lesions [ 68 ], the patient’ symptoms and their extraordinary clinical response to the GFD support the assumption that this patient is affected by a gluten disorder and that the treatment with a GFD seems to be justified. Therefore, we offered the patient a follow up for the surveillance of high risk of complications in the SNCD [ 7 , 69 , 70 ].…”

The Gluten-Free Diet for Celiac Disease: Critical Insights to Better Understand Clinical Outcomes

“…At this point, inadequate adherence to the GFD is a severe handicap for testing and verifying the diagnosis of SNCD [ 1 , 2 , 3 , 4 , 5 ]. Finally, a strict GFD is crucial to avoid developing long-term complications, such as anemia, osteoporosis, and malignancy [ 20 ]. A significant consideration is also the cost of investigating other clinical conditions often associated with CeD, which may also be responsible for persistent symptoms in individuals who claim to be strictly adhering to the GFD.…”