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Pre-endoscopic serological test with duodenal biopsy in high risk patients had high sensitivity and low specificity for coeliac disease
  1. Nina Ruth Lewis, MD,
  2. Richard F A Logan, MD
  1. Queen’s Medical Centre,
 Nottingham, UK

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 Q Does a clinical decision tool (CDT) based on pre-endoscopic serological testing with duodenal biopsy for high risk patients accurately diagnose coeliac disease?

    Clinical impact ratings Gastroenterology ★★★★★☆☆ IM/Ambulatory care ★★★★★☆☆


    Embedded ImageDesign:

    2 cohort studies, 1 for derivation and 1 for validation.

    Embedded ImageSetting:

    endoscopy department at the Royal Hallamshire Hospital, Sheffield, UK.

    Embedded ImagePatients:

    1464 patients in the retrospective derivation cohort and 2000 patients 16–94 years of age (mean age 56 y, 58% women) in the prospective validation cohort who were referred for gastroscopy. Exclusion criteria were previously known coeliac disease, coagulopathy (international normalised ratio >1.3 or platelets <80 x 109/l), active gastrointestinal bleeding, or suspected cancer.

    Embedded ImageDescription of prediction guide:

    the CDT combined pre-endoscopic serological testing (tissue transglutaminase [TTG] antibody) and assessment of symptoms to identify patients at high or low risk of coeliac disease. The CDT was modified in the validation cohort to include duodenal biopsy for all high risk patients. Patients were at high risk if they had indications for weight loss, anaemia (haemoglobin level <120 g/l in women or <130 g/l in men), or diarrhoea (bowel movement frequency >3 times/d). Patients were at low risk if they had atypical symptoms for coeliac disease, including abdominal pain, reflux, dyspepsia, vomiting or nausea, or chest pain.

    Embedded ImageOutcomes:

    diagnosis of coeliac disease.


    61 (4.2%) patients in the derivation cohort and 77 (3.9%) patients in the validation cohort were newly diagnosed with coeliac disease. In the validation cohort, 739 (37%) patients were categorised as high risk and 1261 (63%) were categorised as low risk; the prevalence of coeliac disease was 9.6% in the high risk group and 0.5% in the low risk group. The CDT with pre-endoscopic serological testing and duodenal biopsy in high risk patients had higher sensitivity but lower specificity than did the CDT with pre-endoscopic serological testing only (table). The likelihood ratios are in the table.

    Derivation and validation of a clinical decision tool to diagnose coeliac disease in patients referred for gastroscopy*


    A clinical decision tool based on pre-endoscopic serological testing combined with duodenal biopsy for high risk patients diagnosed all cases of coeliac disease.

    Abstract and commentary also appear in ACP Journal Club.


    Serological testing has shown a high prevalence of coeliac disease (approximately 1%) in many areas including North America where it was previously thought to be uncommon. It has also facilitated diagnosis. However, the protean clinical manifestations of coeliac disease mean that the disease has to be included in the differential diagnosis for many patients. Unfortunately, current serological tests are neither sufficiently sensitive nor specific to be used alone as screening tests in all clinical settings.1

    The categorisation of patients into high and low risk groups according to the CDT by Hopper et al is pragmatic: Important groups, such as patients with a family history or those with conditions associated with coeliac disease, were not considered. In addition, the quantitative element of the TTG assay has been ignored. The pragmatic categorisation resulted in more than one third of patients being considered as high risk of coeliac disease and therefore requiring duodenal biopsy irrespective of the results of the TTG assay. Consequently, in the validation cohort, 739 patients in the high risk group proceeded to upper gastrointestinal endoscopy to diagnose 71 cases of coeliac disease, including 7 cases in 585 high risk patients with a normal TTG test.

    Although Hopper et al maintain that their CDT would be cost effective in reducing the numbers of patients needing duodenal biopsies by 40%, this presupposes that coeliac disease was being considered in the differential diagnosis for these low risk patients. What is clear is that the specificity of the TTG assay alone is poor (90.9%), with the positive predictive value in the high risk group being only 28.6%; relying on the TTG assay alone will result in a considerable number of patients needing duodenal biopsies.

    Nevertheless, the study is an important contribution to improving the diagnosis of coeliac disease: It confirms that in patients at low risk of the condition, a negative result on the TTG assay is sufficient to rule out the diagnosis of coeliac disease.


    View Abstract


    • For correspondence: Dr A D Hopper, Royal Hallamshire Hospital, United Kingdom. andydhopper{at}

    • Source of funding: no external funding.