Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2020; 26(26): 3780-3791
Published online Jul 14, 2020. doi: 10.3748/wjg.v26.i26.3780
Non-invasive prediction of persistent villous atrophy in celiac disease
Barbora Packova, Petra Kovalcikova, Zdenek Pavlovsky, Daniel Bartusek, Jitka Prokesova, Jiri Dolina, Radek Kroupa
Barbora Packova, Jitka Prokesova, Jiri Dolina, Radek Kroupa, Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
Petra Kovalcikova, Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
Zdenek Pavlovsky, Department of Pathology, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
Daniel Bartusek, Department of Radiology and Nuclear Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
Author contributions: Packova B was involved in the conceptualization, data collection, investigation, project administration, writing original draft; Kovalcikova P took part in methodology and was responsible for statistical analysis; Pavlovsky Z was involved in the data collection, investigation; writing review and editing; Bartusek D was involved in the data collection, investigation; writing review and editing; Prokesova J was involved in the data collection, writing review and editing ; Dolina J took part in the supervision and editing; Kroupa R performed the conceptualization, methodology, project administration, supervision, validation, visualization, writing review and editing. All authors have read and approve the final manuscript.
Supported by Ministry of Health, Czech Republic – conceptual development of research organization, No. FNBr, 65269705.
Institutional review board statement: The study protocol was approved by Institutional review board University hospital Brno.
Informed consent statement: All the patients signed informed consent.
Conflict-of-interest statement: The authors do not have any conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Radek Kroupa, MD, PhD, Doctor, Research Assistant Professor, Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, Brno 62500, Czech Republic. kroupa.radek@fnbrno.cz
Received: January 16, 2020
Peer-review started: January 16, 2020
First decision: April 8, 2020
Revised: May 13, 2020
Accepted: July 1, 2020
Article in press: July 1, 2020
Published online: July 14, 2020
Processing time: 179 Days and 18.2 Hours
Abstract
BACKGROUND

Celiac disease (CD) is an immune-mediated enteropathy that is primarily treated with a gluten-free diet (GFD). Mucosal healing is the main target of the therapy. Currently, duodenal biopsy is the only way to evaluate mucosal healing, and non-invasive markers are challenging. Persistent elevation of anti-tissue transglutaminase antibodies (aTTG) is not an ideal predictor of persistent villous atrophy (VA). Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies (aDGP) and abdominal ultrasonography are lacking.

AIM

To evaluate the ability of aTTG, aDGP, small bowel ultrasonography, and clinical and laboratory parameters in predicting persistent VA determined using histology.

METHODS

Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy, levels of aTTG and aDGP, and underwent small bowel ultrasonography were included in this retrospective cohort study. We evaluated the sensitivity, specificity, and positive and negative predictive values of aTTG, aDGP, small bowel ultrasonography, laboratory and clinical parameters to predict persistent VA. A receiver operating characteristic (ROC) curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy prediction.

RESULTS

Complete data were available for 82 patients who were followed up over a period of four years (2014-2018). Among patients included in the analysis, women (67, 81.7%) were predominant and the mean age at diagnosis was 33.8 years. Follow-up biopsy revealed persistent VA in 19 patients (23.2%). The sensitivity and specificity of aTTG using the manufacturer’s diagnostic cutoff value to predict atrophy was 50% and 85.7%, respectively, while the sensitivity and specificity of aDGP (using the diagnostic cutoff value) was 77.8% and 75%, respectively. Calculation of an optimal cutoff value using ROC analysis (13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA) increased the accuracy and reached 72.2% [95% confidence interval (CI): 46.5-90.3] sensitivity and 90% (95%CI: 79.5-96.2) specificity for aDGP IgA and 66.7% (95%CI: 41.0-86.7) sensitivity and 93.7% (95%CI: 84.5-98.2) specificity for aTTG IgA. The sensitivity and specificity of small bowel ultrasonography was 64.7% and 73.5%, respectively. A combination of serology with ultrasound imaging to predict persistent atrophy increased the positive predictive value and specificity to 88.9% and 98% for aTTG IgA and to 90.0% and 97.8% for aDGP IgA. Laboratory and clinical parameters had poor predictive values.

CONCLUSION

The sensitivity, specificity, and negative predictive value of aTTG and aDGP for predicting persistent VA improved by calculating the best cutoff values. The combination of serology and experienced bowel ultrasound examination may achieve better accuracy for the detection of atrophy.

Keywords: Celiac disease; Villous atrophy; Anti-tissue transglutaminase antibodies; Anti-deamidated gliadin peptide antibodies; Abdominal ultrasound; Gluten-free diet

Core tip: We attempted to determine whether indicators such as anti-tissue transglutaminase antibodies (aTTG), anti-deamidated gliadin peptide antibodies (aDGP), and abdominal ultrasonography could predict villous atrophy (VA). We studied patients who were diagnosed with celiac disease and were on a gluten-free diet for at least one year; they were followed up for a maximum of four years. We determined that aTTG and aDGP were not optimal markers of persistent VA. However, we found that a combination of serology and bowel ultrasound examination enabled detection of VA with better accuracy.