Selected symptomatic adults may now be diagnosed with celiac disease without undergoing duodenal biopsy, according to updated British Society of Gastroenterology guidelines that also revise recommendations for testing, biopsy collection, gluten challenge, and follow-up.
The optional no-biopsy pathway applies to symptomatic adults assessed in secondary care whose immunoglobulin A tissue transglutaminase (IgA-tTG) level is at least 10 times the assay’s upper limit of normal. The decision should follow a discussion with the patient, and endoscopy remains appropriate for patients with red-flag symptoms, suspected alternative disease or another reason for upper GI evaluation.
The guideline, which includes 15 recommendations and 19 good practice statements, was published in Gut. It cautions that the no-biopsy approach should not be extended routinely to primary care, screening populations or asymptomatic patients because its predictive accuracy may decline where celiac disease prevalence is low. Laboratories should use assay-specific thresholds and participate in quality assurance.
Some patients may still prefer histologic confirmation before committing to a lifelong gluten-free diet, first author Hugo A. Penny, MBBS, MRCP, PhD, of Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom, and colleagues noted. Biopsy also identifies potential celiac disease and seronegative disease, which a serology-only pathway may miss.
Other key points from the guideline include:
For initial testing, the guideline recommends IgA-tTG as the first-line assay with simultaneous screening for selective IgA deficiency. Patients with IgA deficiency and persistent clinical suspicion should undergo IgG-based serology and upper GI endoscopy with duodenal biopsies.
Patients must continue eating gluten before testing because both serology and histology depend on an immune response to gluten. Those who have already eliminated gluten should undergo a gluten challenge of 3 to 6 grams daily for at least six weeks, with a lower dose and longer duration if needed.
When biopsy is required, endoscopists should obtain at least four specimens from the second portion of the duodenum and two from the bulb, preferably in separate containers, because adequate sampling improves diagnostic yield.
Diagnosis may be established when positive serology is accompanied by increased intraepithelial lymphocytes and crypt hyperplasia, with or without villous atrophy. HLA typing should generally be reserved for selected cases, primarily to exclude celiac disease because the absence of HLA-DQ2 or HLA-DQ8 makes the diagnosis highly unlikely.
The guideline also broadens case finding. Physicians should test patients with persistent unexplained GI symptoms, weight loss, prolonged fatigue, severe mouth ulcers or unexplained iron, folate or vitamin B12 deficiency, and consider testing in those with unexplained neurologic symptoms, elevated liver enzymes, low bone density, subfertility or recurrent miscarriage. High-risk groups include first-degree relatives and patients with type 1 diabetes, autoimmune thyroid disease, inflammatory bowel disease and microscopic colitis.
A lifelong gluten-free diet remains the only accepted treatment, but the guideline places greater emphasis on specialist dietitian involvement and nutritional quality. Newly diagnosed patients should be referred to a dietitian with celiac expertise and connected with a reliable patient organization. Gluten-free oats may be introduced at the start of treatment if certified gluten-free and accompanied by clinical follow-up.
The authors emphasize that no single measure reliably assesses dietary adherence. They recommend combining dietitian assessment, symptom review, dietary tools and serology because normal tTG levels do not confirm strict gluten avoidance or mucosal healing.
All patients should receive regular follow-up for up to two years after diagnosis to assess symptoms, dietary adherence and nutritional status. Clinically stable patients may then transition to patient-initiated follow-up, while those with persistent symptoms, poor adherence or complications should continue structured care. Repeat biopsy is not mandatory for every asymptomatic patient but should be considered when planning long-term management because histology remains the only reliable way to assess mucosal healing.
Persistent symptoms warrant systematic reassessment because ongoing gluten exposure is the most common cause, although disorders of gut-brain interaction, microscopic colitis, inflammatory bowel disease and slow mucosal healing should also be considered. Patients with suspected refractory celiac disease should be referred to specialist centers. Open-capsule budesonide is recommended as first-line treatment for type 1 refractory disease.
For practicing physicians, the guidance supports fewer biopsies in a carefully selected minority while emphasizing rigorous diagnostic standards, adequate biopsy sampling, and structured follow-up for all other patients.
Dr. Penny and several coauthors reported honoraria, consulting or advisory roles, research funding, grants, patents, or other support from pharmaceutical, biotechnology and diagnostic companies. Some also reported roles with Coeliac UK.
Expert Insight
GI & Hepatology News asked Christopher Cao, MD, director of the Celiac Disease Program at Mount Sinai Hospital, New York, to weigh in on the guidelines.
Which updated recommendations are most likely to change how gastroenterologists diagnose and manage celiac disease in routine practice?
Dr. Cao: Beyond the optional non-biopsy pathway, one of the most important updates is the emphasis that celiac disease requires structured longitudinal care rather than simply establishing a diagnosis. The recommendations regarding health care maintenance — bone density scans, pneumococcal vaccines, assessing nutritional deficiencies, supporting psychological well-being — and consideration of a repeat endoscopy to assess villous healing provide a comprehensive framework for ongoing management.
Which patients are appropriate for the new no-biopsy diagnostic pathway, and when should duodenal biopsy remain essential?
Dr. Cao: These guidelines state that a non-biopsy pathway would be intended for selected symptomatic adults being evaluated in secondary care, and not as a blanket diagnostic strategy for primary care. This distinction is important because the performance of diagnostic testing depends on disease prevalence and the pre-test probability of the disease. Prior research showing high positive predictive value and specificity of a IgA-tTG > 10x ULN in diagnosing celiac disease were performed in celiac centers, where pre-test probability of celiac disease was substantially higher than in unselected primary care populations. In settings with low celiac disease suspicion or prevalence, such testing may not be as accurate.
Additionally, these guidelines note the non-biopsy approach should be adopted only after shared decision-making with the patient.
My take home from these guidelines is that a non-biopsy approach is an option for select patients but should only be utilized in secondary care after shared decision-making with the patient. Importantly, the guideline does not extend the non-biopsy approach to primary care, where disease prevalence and pre-test probability differ substantially from secondary care. Confirmation of diagnosis within secondary care also helps reduce the risk of decentralizing celiac disease management, ensuring that patients receive expert dietary counseling, appropriate health care maintenance, and longitudinal follow up.
How should physicians apply the new follow-up recommendations, particularly regarding repeat biopsy, bone-density testing and long-term monitoring?
Dr. Cao: These guidelines provide a framework to help guide celiac follow-up care. They advocate for regular follow-up for 2 years after diagnosis and transitioning to a gluten-free diet. During this time, follow-ups should be provided by a provider and dietitian who have experience with celiac disease.
Additional recommendations made during follow-up include a bone density scan at one year after initiation of a gluten-free diet, a pneumococcal vaccine at the time of diagnosis, assessing for nutritional deficiencies, and consideration of a repeat endoscopy 1-2 years after starting a gluten-free diet to re-evaluate villous histology. Importantly, duodenal histology remains the standard for assessing mucosal healing.
Dr. Cao serves as the site principal investigator for a few celiac disease clinical trials but has no financial interests in, or consulting fees associated with, any of these trials.