CD: Villous Atrophy (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To investigate whether the tissue transglutaminase antibody test could substitute biopsy in dietary assessment and whether the test is better than the endomysial antibody test in follow-up.
Inclusion Criteria:
Diagnosis initially based on small bowel mucosal villous atrophy and crypt hyperplasia.
Exclusion Criteria:
Patients with selective IgA deficiency not included.
Description of Study Protocol:

Recruitment

Consecutive adult celiac patients enrolled.

Design

Controlled cross-sectional and follow-up study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Gluten-free diet.

Statistical Analysis

Fisher's exacttest was used in cross-tabulations.  P values lower than 0.05 were considered statistically significant.

Data Collection Summary:

Timing of Measurements

Antibodies determined in patients and all underwent small bowel biopsy.

Dependent Variables

  • Serum IgA-class tissue transglutaminase antibodies determined by ELISA 
  • Serum IgA-class endomysial antibodies determined through indirect immunofluorescence method 
  • Small bowel biopsy specimens taken from the distal part of the duodenum upon endoscopy.  Mucosal morphology interpreted with Marsh's classification.  Marsh 3 was considered inadequate mucosal recovery during the diet. 

Independent Variables

  • Gluten-free diet.  Dietary compliance evaluated by dietitian through interview and 3 day food record.  The diet was regarded as strict when no additional gluten intake was shown.  Patients were considered to have dietary transgressions when admitting every week or at least once a month occasional consumption of gluten-containing foods, such as bread or cake.

Control Variables

 

Description of Actual Data Sample:

Initial N: 87 celiac adults, 63 women, 24 men

Attrition (final N):  87 adults.

Age:  Mean age 49 years (range 22-73 years) 

Ethnicity: Not mentioned.

Other relevant demographics:  Median duration of gluten-free diet of 1 year (range 1 - 18 years)   

Anthropometrics 

Location:  Finland

 

Summary of Results:

Other Findings

In the dietary assessment, 76 out of 87 (87%) celiac disease patients adhered to a strict gluten-free diet.

Of 87 celiac patients, 27 showed Marsh 3 villous atrophy on gluten-free diet.  Of these 27, tissue transglutaminase antibody was within normal limits in 16 (59%) and endomysial antibody in 20 (74%), (P = 0.12).  Thus, the sensitivity of tissue transglutaminase antibody in revealing a severe mucosal lesion was only 41%.

2 out of 29 (7%) with normal mucosa (Marsh 0) had positive tissue transglutaminase antibodies.

6 out of 11 (55%) admitting regular dietary lapses remained tissue transglutaminase antibody negative.

In the follow-up, serum IgA-class tissue transglutaminase antibody was initially positive in 28 out of 30 (93%) untreated patients.  Even a significant decrease in tissue transglutaminase antibody did not guarantee mucosal recovery.

Author Conclusion:
A substantial number of celiac patients with negative tissue transglutaminase or endomysial antibodies may still have manifest mucosal villous atrophy.  Small bowel biopsy is therefore still necessary to ensure that the gluten-free diet is adequate.  To conclude, we consider that tissue transglutaminase or endomysial antibodies have some use in evaluating the adequacy of a gluten-free diet.  However, the test is not sensitive enough to reveal dietary regressions or poor small bowel mucosal recovery in celiac disease, and hence cannot substitute the control biopsy.
Funding Source:
Industry:
Research fund of Astra Zeneca
Pharmaceutical/Dietary Supplement Company:
University/Hospital: Tampere University Hospital, Academy of Finland
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:
Dietary compliance was monitored by dietitian.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? Yes
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) Yes
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes