Abstract

Abstract Background Non-erosive reflux disease (NERD) accounts for over half of all cases of gastroesophageal reflux disease (GERD). It is characterized by symptoms of GERD with pathologic acid exposure on ambulatory pH monitoring and no evidence of erosive esophagitis on upper endoscopy. Symptoms and negative endoscopy alone are insufficient to diagnose NERD. Ambulatory pH monitoring is limited due to availability and patient tolerance. Conventional histologic analysis of mucosal esophageal biopsies has been studied in this context but there is no clear guidance as to its utility in diagnosing NERD. Aims The purpose of this study was to conduct a systematic review and meta-analysis to determine the sensitivity and specificity of esophageal biopsy histology in diagnosing NERD. Methods Data were obtained from Embase (1947- April 2021) and Ovid MEDLINE (1946 – April 2021). We included all studies where esophageal mucosal biopsies were taken and light microscopy was used to analyze histopathology in symptomatic adult NERD patients (i.e., no evidence of erosive esophagitis and ambulatory pH testing confirmed the presence of pathologic acid exposure). Papers were sorted in duplicate. Relevant data was extracted from papers meeting inclusion criteria, including histologic abnormalities and the location of the biopsy. Sensitivities and specificities were calculated from raw data and pooled using RevMan 5.4 software, using asymptomatic patients with no significant esophageal acid exposure and/or patients with functional heartburn (i.e., symptoms but no elevated acid exposure on ambulatory pH testing) as controls. Results The search yielded 2871 studies after the removal of duplicates, of which 158 were eligible for full text review. In total, 12 papers met our stringent inclusion criteria and contained raw data that allowed for sensitivity calculations. Histological abnormalities that were commonly reported included gross morphological scores, papillary elongation, basal cell hyperplasia and dilated intraepithelial spaces. Biopsies were taken at <3cm in 5 studies, ≥3cm in 5 studies, and at multiple sites in 2 studies, and all were reviewed by a blinded pathologist. When assessing for the presence of any abnormality in the histological analysis, biopsies taken at <3cm had a pooled sensitivity of 0.70 (95% CI 0.64 – 0.75) and specificity of 0.72 (95% CI 0.63 – 0.77). Biopsies taken at ≥3cm revealed a pooled sensitivity of 0.39 (95% CI 0.32 – 0.47) and specificity of 0.63 (95% CI 0.51 – 0.74). Conclusions Esophageal mucosal biopsies have poor sensitivity and specificity at diagnosing non-erosive gastroesophageal reflux disease. Biopsies taken below 3cm appear to have a higher sensitivity and specificity than those taken more proximally. Funding Agencies None

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