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Factors Associated With Villous Atrophy In Symptomatic Celiac Disease Patients On A Gluten-Free Diet

A person on a gluten diet is likely to be influenced by the auto-immune injury to the lining of the small bowel that results in Celiac Disease. This disease is mainly an immune-related disease, which is chronic and intestinal. This can be caused by the consumption of wheat, barley, rye and derivatives. This is characterized by small inflammation consequences that seem to be widespread and are linked to diverse manifestations. This is not only a gastrointestinal disease because this also affects several other organs and can also show non-gastrointestinal symptoms and can also be completely asymptomatic. A strict gluten-free diet is the only treatment for patients suffering from Celiac Disease. Avoidance of gluten can reverse the clinical features of this Celiac Disease. Lifelong adherence of a gluten-free diet is the only known treatment for Celiac Disease. People following gluten-free diet find it to be extremely burdensome, socially restrictive and also extremely expensive. While some people have adjusted to this situation, others seem to be constantly struggling.

Maximum percentage of the population with celiac disease do not fix their small bowel mucosa even after going gluten-free. Persistent Villus Atrophy is found prevalent in patients who undergo follow-up biopsy. This has been found to be asymptomatic in patients with celiac serology and this is different from refractory celiac disease. The method to identify this disease in patients is by doing a duodenal mucosal biopsy which demonstrates crypt hyperplasia, intraepithelial lymphocytosis and villous atrophy. The identification of this disease is important because most of the follow-up with the symptomatic celiac disease did not have any previous medical history and despite a gluten-free diet, duodenal injury can be found in these patients. In this article, we will try to figure out the clinical risk factors for persistent villous atrophy in symptomatic celiac disease patients.

Villous Atrophy and Symptomatic Celiac Disease

Villous Atrophy and Symptomatic Celiac Disease

Celiac Disease is a genetic and autoimmune disorder that affects 1-2% North American people1, 2 and it is important for the patients to have a gluten-free diet, as gluten is known to act as a trigger that attacks the immune system of the intestine villi.

In the small intestine, there is a line of the wall that looks like fingers and is microscopic, called the intestine villi. It is responsible for absorbing the nutrients present in the food. When this wall erodes away and leaves behind a virtually flat surface, it can cause a serious nutrient deficiency. The main cause of Villous Atrophy is Celiac Disease.

When the worst-case scenario is taken into consideration, the villi can be destroyed completely and people become prone to malnutrition and the chances of suffering from lymphoma increases. The only way of knowing if a person is suffering from Villus Atrophy is by looking directly inside the small intestine to see if the walls are intact or not.

Doctors use endoscopy (it is a process in which doctors thread a device along with a small camera as well as other essential instruments down the throat, through the stomach and in the small intestine) to look what is there. Another way of looking into the intestine for villous atrophy is through Capsule Endoscopy in which a pill is swallowed that contains a camera. The intestinal biopsy confirms 3 things, whether the person has celiac disease; if the symptoms are likely to improve on a gluten-free diet because of the placebo effect; and if the patient has a different gastrointestinal disorder or sensitivity that changes itself in correspondence to the diet.

If the result from the test of screening or antibody is positive, it is possible that the doctor may suggest endoscopic biopsy for the small intestine. It allows the doctor to see what is going on inside the GI tract.

Identification of Celiac Disease

Persistent Villous atrophy has been associated with lymphoproliferative malignancy as well as osteoporotic fractures. Patients having Celiac disease are found to be at a greater risk of high mortality compared to the rest. Evidence linking of persistent villous atrophy with increased mortality is also lacking. Celiac disease management focuses on increasing mucosal healing with duodenal biopsy follow-up in order to confirm histologic emission, which is becoming more and more evident in patients who have ongoing symptoms. Materials and methods used for the identification of this disease are the study of population and duodenal biopsy. A clinical trial was conducted in order to ascertain the association between the clinical factors including the symptoms, medication use, laboratory findings, and the risk of persistent villous atrophy in the celiac disease patients who are following a gluten-free diet and are undergoing a protocol mandated duodenal biopsy prior to entering the clinical trial. In the trials, adults were shortlisted with celiac disease from the United Kingdom, North America, Finland and Ireland. These people were asked to be on a gluten-free diet for a year in order to develop persistent symptoms and were required to be diagnosed by a physician in order to get screened.

Symptoms were reported to be just one; and it was gastrointestinal problems of moderate to severe intensity within 28 days of screening. The diary session of about 28 days was taken. These records reported the severe condition of diarrhea, bloating, abdominal pain, nausea and tiredness. The outcome of this result stated that the villous height and crypt depth ratio was less than 2.0 in the patients.

Factors and Symptoms Associated with Villous Atrophy

The symptoms and factors linked to persistent villous atrophy are prominent in people of older age, males and people of lower educational strata. Children are more likely to normalize their duodenal history than an adult; the association of gastrointestinal symptoms and persistent villous while on a gluten-free diet has been very prominent. The use of non‐steroidal anti‐inflammatory drugs (NSAIDs), angiotensin‐receptor blockers including the proton-pump inhibitor scan is connected to the enteropathy that is induced by the drug. This is considered as an authentic method. On the other hand, the impact of these medications on the villous atrophy is not confirmed by the researcher.

A separate analysis was done with patients who suffer celiac disease. A total of 1345 patients volunteered for the screening process out of which 38% of the patients showed persistent villous atrophy that came due to gluten free diet3. The medications were classified further. The patients had reported that they had nausea, bloating and pain in the abdominal region. The study proves that the people who suffer with celiac disease are definitely associated with villous atrophy on a persistent note. This is one of the largest studies that have been done in this concept. This study makes use of protocol specified, the symptoms and laboratory values to come up with a quantitative interpretation. In addition, this can also be considered as the first study to evaluate the relationship between mucosal healing and the use of medications in this disease. The Diagnostic value as determined with the symptoms of patients who suffer persistent villous atrophy has not been confirmed and can be termed as asymptomatic.

Typical symptoms of celiac disease were reported as anemia, weight loss, diarrhea, constipation, diffuse abdominal pain, and heartburn. Endoscopic biopsy is frequently performed on patients with celiac disease due to its prognostic significance. It might also be performed in order to determine the cause of persistent symptoms despite a gluten-free diet. About 60% of the patients in the study lacked the symptoms of villous atrophy; therefore, a majority of the patients who enrolled in the study were likely to have symptoms other than active celiac disease.

Villous Atrophy in Symptomatic Celiac Disease Patients on Gluten-free Diet

Despite the continuation of a gluten-free diet, in some of the celiac disease patients, the duodenal injury continues to persist.

The above study involved a cross-sectional analysis performed on patients on a gluten-free diet suffering from celiac diseases having symptoms that are severe or moderate. These patients went through protocol-mandate duodenal biopsy. Factors like demography, type of symptoms, usage of medication, and serology were examined to find out the predictors of persisting villous atrophy.

In the study of 1345 patients, 35%-41% were diagnosed with active celiac disease along with persistent villous atrophy1. Older age patients ranging from 18-29 were found to be on a greater risk of losing their lives if they continued the gluten-free diet for a long time3. Males were more likely to develop persistent villous atrophy than females. About 62% of people over 70 years of age were reported to have symptoms of persistent atrophy villous. Around 52% of the people who were on a gluten-free diet for less than 2 years were at a higher risk of the primary outcome. Around 87% of the patients reported bloating, 84% reported abdominal pain and tiredness and 76% of the patients were reported to have diarrhea. The patients who showed symptoms of anemia, heartburn, and hypertension were more likely to develop persistent villous atrophy.

Out of a total of 1345 patients suffering from symptomatic celiac disease, 511 were found to have active celiac disease with continuous villous atrophy. After a series of analysis and evaluation of the research, it was found out that the risk factor for this was more in older age while a gluten-free diet was protective. Villous Atrophy was linked with things like usage of proton-pump inhibitors, non-steroidal anti-inflammatory drugs as well as few of the selective serotonin reuptake inhibitors.


Symptoms were no likely predictive of persistent mucosal injury. The study reported that mucosal healing is not at all possible in patients with celiac disease despite their gluten-free diet. The impact of the use of NSAIDs, PPIs, and SSRIs appeared to be linked only to impair mucosal healing. The study further showed that the symptoms associated with celiac disease were a poor predictor of any histologic damage related to the follow-up in the celiac disease.

The study further proved that there was a presence of duodenal injury in patients with celiac disease despite their gluten-free diet. This is also related to adverse effects. Symptom type, demographic factors, medication use, and serology were used to determine the risk factors of persistent villous atrophy. A gluten-free diet was reported as the treatment of patients with celiac disease, but the study proves that despite gluten-free diet, they still have it. There have also been some trials regarding alternative measures for the treatment of celiac disease.


  1. NIH Consensus Development Conference on Celiac Disease. NIH Consens State Sci Statements. 2004;21(1):1–23.
  2. AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease.Gastroenterology. 2006;131(6):1977–1980.
  3. https://www.ncbi.nlm.nih.gov/pubmed/28220520

Also Read:

Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:July 19, 2021

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