EAL

CD: Villous Atrophy (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the endoscopic and histopathologic appearance of the duodenum of a chort of celiac disease patients following a gluten-free diet.

Inclusion Criteria:

Presentation with diarrhea, biopsy-proven celiac disease (diagnosis reconfirmed by review of original biopsy), good clinical response to the gluten-free diet (resolution of diarrhea), follow-up endoscopy with biopsy specimens obtained at the center after at least 1 year of diet therapy, and follow-up endoscopy during the 2 years before initiating the study.

Exclusion Criteria:

Excluded if not included above.

Description of Study Protocol:

Recruitment

Patients seen at the Celiac Disease Center. Consecutive patients identified meeting inclusion criteria.

Design

Retrospective review of cohort, nonrandomized clinical trial.

Blinding used (if applicable)

Endoscopist not blinded as to condition of patient. Blinded review of initial diagnostic and post-treatment biopsy specimens.

Intervention (if applicable)

Gluten-free diet for a mean of 8.5 years (range 1 - 45 years).

Statistical Analysis

Differences between diagnostic and follow-up biopsies determined by using the Student's t test. Results are expressed as mean +/- SD.

Data Collection Summary:

Timing of Measurements

Endoscopic and histopathologic appearances of the duodenal mucosa were reviewed.

Dependent Variables

Endoscopy performed by 1 endoscopist. Endoscopic appearance of descending duodenum classified as normal (at least 3 folds per endoscopic field), reduced or absent duodenal folds, scalloping of folds, fissures, and mosaic or nodular appearance of the mucosa.
At least 6 biopsy specimens were taken from the descending duodenum with standard forceps. Histopathologic findings reviewed by a single pathologist and classified as total villous atrophy (crypt:villous ratio of 1:0 - 1:1), partial villous atrophy (crypt:villous ratio of 1:1 - 1:4) or normal (crypt:villous ratio of 1:4).)
Antiendomysial (EmA) and antigliadin (AGA) antibody determinations at the time of follow-up were also reviewed. Serologic tests obtained from commercial labs.

Independent Variables

Gluten-free diet: a physician familiar with the gluten-free diet assessed all patients for compliance.

Control Variables

Description of Actual Data Sample:

Initial N: Original database contained 180 patients. 39 adult patients included, male:female ratio = 1:1.7. Diagnostic and follow-up biopsies analyzed for 12 patients.

Attrition (final N): See above.

Age: Mean age 52 years, range 20 - 74 years.

Ethnicity: Not mentioned.

Other relevant demographics: Not mentioned.

Anthropometrics

Location: New York

Summary of Results:

Other Findings

Endoscopic appearance was normal in 9 (23%) patients, reduced duodenal folds were present in 46%, scalloping of folds in 33%, mucosal fissures in 44%, and nodularity in 33%. There was more than 1 abnormality present in 46%.

Histology was normal in only 8 (21%) patients. The remainder had villous atrophy, 27 (69%) partial, 4 (10%) total.

Paired (diagnostic and follow-up) biopsy specimens were reviewed blindly for 12 patients who had followed a gluten-free diet for a mean of 4 years, range 1 -14 years. The mean intraepithelial lymphocyte count fell from 61 +/- 22 to 38 +/- 17 (p < 0.005, normal <30 per 100 epithelial cells) and the crypt-to-villous ratio improved in all except 1 patient (p < 0.001) although it did not normalize.

Serologic results (EmA, AGA) at follow-up were available for 31 of 39 patients. In 24 patients (77%) the serologic results were negative. Antigliadin antibodies were positive in 7 patients, IgA and IgG in 3, and IgG only in 4, whereas 1 patient had a positive EmA.

Author Conclusion:

This study demonstrated that despite adherence to a gluten-free diet and a good clinical response, abnormal endoscopic and histopathologic appearances persist in the majority of patients with celiac disease.

Funding Source:

University/Hospital:

Columbia University College of Physicians and Surgeons

Reviewer Comments:

Dietary compliance assessed by physician but not describd. Small sample size for biopsy comparison. Small cohort.

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?		???
	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?	???
3.	Were study groups comparable?		N/A
	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?	N/A
	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.)	N/A
	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?		???
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	???
	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.)	???
	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?		N/A
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes