Persistent villous atrophy in coeliac disease
Persistent villous atrophy can affect people with coeliac disease despite following a gluten-free diet. We analyse its causes, risks and clinical management.
Persistent villous atrophy in coeliac disease
For most people with coeliac disease, a gluten-free diet helps to control symptoms, promote intestinal recovery and reduce the risk of long-term complications. However, not all patients experience a complete recovery of the intestinal mucosa at the same rate.
In some cases, intestinal villous atrophy may persist despite following a gluten-free diet. This condition, known as persistent villous atrophy (PVA), has attracted growing clinical interest due to its possible link with the progression of the disease and with certain long-term complications.
What is persistent villous atrophy (PVA)?
Persistent villous atrophy is usually defined as the continued presence of lesions consistent with partial or greater atrophy (Marsh ≥3a) several years after starting a gluten-free diet.
Although the exact definition may vary slightly between studies and clinical guidelines, PVA is generally considered to be present when the intestinal mucosa has not regained its normal structure after two or three years of dietary treatment.
The significance of this situation lies in the fact that histological recovery does not always coincide with clinical improvement. In fact, some patients may appear to be well whilst still presenting with significant intestinal abnormalities.
Why does atrophy persist despite a gluten-free diet?
The persistence of villous atrophy may have various causes and does not always imply a complete lack of response to treatment:
How PVA is assessed: the role of duodenal biopsy
The duodenal biopsy remains the gold standard for assessing the recovery of the intestinal mucosa. Although it is an invasive test, it remains the most reliable method for confirming whether the intestinal villi have healed correctly following the start of a gluten-free diet. One of the current challenges is that not all patients undergo a follow-up biopsy and, furthermore, there are still few non-invasive tools capable of assessing histological recovery with the same precision. Therefore, when the clinical response is insufficient or there are doubts about the patient’s progress, it may be necessary to consider a re-evaluation via biopsy.
Prevalence and risks of persistent villous atrophy
The information available on persistent villous atrophy has increased in recent years, enabling us to better understand its frequency and potential clinical consequences.
A prevalence that could reach 23% of patients
Some studies suggest that PVA may affect up to 23% of people with coeliac disease. However, the figures do vary between studies due to differences in diagnostic criteria, follow-up periods and the characteristics of the populations studied. In any case, these data indicate that the persistence of intestinal lesions is not an exceptional occurrence.
Associated complications and mortality
Furthermore, the available evidence suggests that PVA may be associated with an increased risk of certain complications related to coeliac disease. These include:
- Autoimmune disorders.
- Bone problems.
- Certain serious lymphoproliferative complications.
The most widely accepted hypothesis is that persistent intestinal inflammation may contribute to the development of tissue damage and long-term complications. For this reason, complete healing of the intestinal mucosa is increasingly regarded as a key objective in the management of coeliac disease.
Risk factors and tools for identifying patients at higher risk
Early identification of patients at higher risk of PVA can help to tailor clinical follow-up.
Factors that have been associated with an increased likelihood of developing persistent villous atrophy include:
- Diagnosis of coeliac disease after the age of 45.
- Classical presentation of the disease.
- Persistence of symptoms after starting a gluten-free diet.
- Poor adherence to the dietary treatment.
Based on these factors, predictive tools have been developed to identify which patients might benefit from closer monitoring or further investigations.
Clinical implications for the management of coeliac disease
The available data reinforce the importance of individualised monitoring of all people with coeliac disease.
This is because, despite appearing clinically well, some patients may have persistent villous atrophy. For this reason, the assessment of intestinal recovery should not be based solely on the disappearance of symptoms.
Furthermore, recent research suggests that complete mucosal recovery may take longer than was traditionally thought. In some cases, an assessment carried out two to three years after diagnosis could provide a more accurate picture of intestinal healing.
All of this highlights the need to combine clinical follow-up, dietary assessment and, where indicated, histological evaluation in patients with coeliac disease.
Frequently asked questions
What do these findings contribute to clinical practice?
Persistent villous atrophy represents one of the main challenges in the management of coeliac disease.
Although a gluten-free diet remains the cornerstone of treatment, complete recovery of the intestinal mucosa is not always immediate or uniform. Therefore, identifying patients at higher risk and tailoring follow-up to their needs can help prevent complications and improve long-term management of this condition.
You may also be interested in...
Buckwheat in a gluten-free diet: safety and nutritional value
Read more: Buckwheat in a gluten-free diet: safety and nutritional value
Coeliac disease and irritable bowel syndrome: new clinical evidence
Read more: Coeliac disease and irritable bowel syndrome
Coeliac disease and metabolic syndrome: why it is important to discuss nutritional balance
Read more: Coeliac disease and metabolic syndromeSources
References
- Fernández-Bañares F, Beltrán B, Salas A, et al. Persistent Villous Atrophy in De Novo Adult Patients With Celiac Disease and Strict Control of Gluten-Free Diet Adherence: A Multicenter Prospective Study (CADER Study). Am J Gastroenterol. 2021;116(5):1036-1043. doi:10.14309/ajg.0000000000001139
- Schiepatti A, Maimaris S, Raju SA, et al. 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. Gut. 2023;72(11):2095-2102. doi:10.1136/gutjnl-2023-329751
- Lebwohl B, Murray JA, Rubio-Tapia A, Green PHR, Ludvigsson JF. Predictors of persistent villous atrophy in coeliac disease: a population-based study. Aliment Pharmacol Ther. 2014;39(5):488-495. doi:10.1111/apt.12621
- Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease. Am J Gastroenterol. 2013;108(5):656-676. doi:10.1038/ajg.2013.79
- Kaukinen K, Peräaho M, Lindfors K, et al. Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease. Aliment Pharmacol Ther. 2007;25(10):1237-1245. doi:10.1111/j.1365-2036.2007.03311.x