#GUTBlog: Clinical outcomes of potential coeliac disease: a systematic review and meta-analysis

Professor El-Omar has selected Dr Mohamed Shiha from the Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK to do the next #GUTBlog. Dr Shiha is the first author on this paper.

The #GUTBlog focusses on the paper “Clinical outcomes of potential coeliac disease: a systematic review and meta-analysis” which was published in paper copy in GUT in December 2024.

Dr Shiha writes:

“The best research questions often arise from knowledge gaps we encounter in everyday clinical practice. Although the diagnosis of coeliac disease is relatively straightforward, not all patients fit into our established diagnostic criteria. Patients who present with positive serological markers for coeliac disease but have normal duodenal biopsies fall into a diagnostic grey zone known as potential coeliac disease (PCD). This leaves patients and clinicians with more questions than answers: What does this diagnosis mean for patients? What is the risk of progression to overt coeliac disease? Should patients be started on a gluten-free diet, or is regular follow-up sufficient?

We aimed to answer these clinical questions in our recent systematic review and meta-analysis published in Gut[1]. We included over 1000 patients with PCD from 17 studies published between 2002 and 2023. All patients had positive tissue transglutaminase antibodies and/or endomysial antibodies with preserved duodenal mucosa at the time of diagnosis. Approximately a third of patients with PCD who continued to consume gluten progressed to overt coeliac disease, defined by the development of villous atrophy, during follow-up. Interestingly, a similar proportion of patients experienced normalisation of their coeliac serology despite a gluten-containing diet. Among those who adhered to a gluten-free diet (GFD), almost 90% reported symptomatic improvement.

While our study addressed some key questions, it also raised several important new ones. We demonstrated that there is a significant risk of progression to overt coeliac disease in patients with PCD, which supports the role of regular follow-up and repeat biopsies in those who remain on a gluten-containing diet. However, the possibility of serological normalisation without dietary intervention also suggests that not all patients with PCD require immediate treatment with a GFD. Future research should aim to identify which patients with PCD are at a higher risk of developing villous atrophy based on their baseline serological levels, genetic markers and clinical presentations.

Despite having normal duodenal architecture, patients with PCD have a similar clinical presentation to those with coeliac disease and villous atrophy [2]. Most symptomatic patients with both conditions benefit from a GFD, which invites further investigation into the relationship between symptoms and the presence or absence of villous atrophy.  Understanding the true triggers of symptoms, whether related to specific immune responses, alternation of gut microbiota, or disturbance of gastrointestinal motility, could provide valuable insights into managing both PCD and coeliac disease.

Our study provides evidence that could help clinicians and patients make informed decisions about managing PCD. The decision to initiate a GFD should be individualised, taking into account the patient’s symptoms and preferences. This shared decision-making approach may improve outcomes and adherence to treatment while avoiding unnecessary dietary restrictions.”

References

1 Shiha MG, Schiepatti A, Maimaris S, et al. Clinical outcomes of potential coeliac disease: a systematic review and meta-analysis. Gut 2024; gutjnl-2024-333110. doi:10.1136/gutjnl-2024-333110

2 Newton M, Greenaway EA, Holland WJ, et al. What are the clinical consequences of ‘potential’ coeliac disease? Dig Liver Dis 2023;55:478–84. doi:10.1016/j.dld.2022.10.019

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