CLINICAL REVIEWSThe Natural Course of Gastroesophageal Reflux Disease A Critical Appraisal of the LiteratureShah, Aun MD; Shibli, Fahmi MD; Kitayama, Yoshitaka MD, PhD; Fass, Ronnie MD, FACGAuthor Information The Esophageal and Swallowing Center, Digestive Health Center, Division of Gastroenterology and Hepatology, MetroHealth Medical System, Case Western Reserve University, Cleveland, OH The authors declare that they have nothing to disclose. Address correspondence to: Ronnie Fass, MD, FACG, The Esophageal and Swallowing Center, MetroHealth Medical Center, Division of Gastroenterology and Hepatology, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH 44109 (e-mail: [email protected]). Journal of Clinical Gastroenterology: January 2021 - Volume 55 - Issue 1 - p 12-20 doi: 10.1097/MCG.0000000000001419 Buy Metrics Abstract Interpreting natural course studies have been very difficult due to their retrospective design, lack of standardization, reliability of reported mucosal findings, liberal use of antireflux medications and accuracy of chart documentation. Studies provided a wide range of progression rates of patients from nonerosive reflux disease (NERD) to erosive esophagitis (EE). However, direct progression from NERD to Barrett’s esophagus appears to be an uncommon phenomenon. Importantly, progression of NERD patients was commonly reported to low grades of EE, which are currently considered inconclusive of gastroesophageal reflux disease. Reports of progression rates from low grades to high grades EE also vary considerably. Progression of patients with EE, without metaplastic epithelium underneath the inflammation, to Barrett’s esophagus is relatively uncommon. Recently, it was also recognized that regression from high grades to low grades EE and from EE to NERD is a common phenomenon affecting up to 25% of the patients from each group. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.