The Long-Term Natural History of Gastroesophageal Reflux Disease

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Long-term gastric acid suppression has been suggested as a means to prevent complications of reflux esophagitis. We report on the 20-year follow-up of 2,306 patients with at least two endoscopic examinations who were taking no antisecretory medication before baseline endoscopy and whose long-term treatment was determined by reflux symptoms.


From 1979 through 1998, endoscopy and biopsy were performed in the Hines Veterans Affairs Hospital endoscopy clinic by three endoscopists. Antireflux treatment was symptom-driven, and endoscopies were repeated mostly for symptomatic recurrence due to cessation of therapy.


Of 4,633 patients undergoing endoscopy for reflux symptoms, 2,306 had at least one follow-up endoscopy and biopsy. Over a mean follow-up period of 7.6 years (range, 1–20 years), the esophageal mucosa of 67% of patients remained unchanged, that of 21% improved, and that of 11% worsened. Esophageal stricture requiring dilation developed from a normal baseline mucosa in one of 1,313 patients (0.08%) and from an erosive baseline mucosa in 18 of 957 patients (1.9%). The overall incidence of stricture in patients with gastroesophageal reflux (GER) disease was <1/1,000 per year. Nonsteroidal anti-inflammatory drug (NSAID) consumption was associated with less mucosal improvement (odds ration [OR]=0.67; confidence interval [CI]=0.46–0.98). Use of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) was associated with mucosal improvement (OR for PPIs=1.49; CI=1.14–2.17). Cohn's kappa was 42%, confirming the results that demonstrate stability of esophageal mucosal disease in the majority of patients.


Symptom-driven treatment of GER disease after a thorough endoscopic examination to exclude premalignant or malignant esophageal mucosal disease is practical and safe for the vast majority of patients with uncomplicated GER symptoms.

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