Changes of Gastric Mucosal Architecture During Long-Term Omeprazole Therapy: Results of a Randomized Clinical Trial

Aliment Pharmacol Ther. 2006 Mar 1;23(5):639-47. doi: 10.1111/j.1365-2036.2006.02792.x.


Background: The impact of long-term acid suppression on the gastric mucosa remains controversial.

Aim: To report further observations on an established cohort of patients with gastro-oesophageal reflux disease, after 7 years of follow-up.

Methods: Of the original cohort randomized to either antireflux surgery or omeprazole, 117 and 98 patients remained in the medical and surgical arms, respectively. Gastric biopsies were taken at baseline and throughout the study.

Results: Fifty-three antireflux surgery and 39 omeprazole-treated patients had Helicobacter pylori infection at randomization. Eighty-three omeprazole-treated and 60 antireflux surgery patients remained H. pylori negative over the 7 years, and no change was observed in mucosal morphology except for a change in endocrine cell population (linear and diffuse hyperplasia, P = 0.03). During the 7-year study many patients, who were initially H. pylori infected, had the infection eradicated leaving only 13 omeprazole and 12 antireflux surgery patients still infected. In these patients, omeprazole induced a deterioration of the mucosal inflammation scores (P = 0.01) with a numerical increase of glandular atrophy.

Conclusions: Long-term omeprazole therapy does not alter the exocrine oxyntic mucosal morphology in H. pylori-negative patients, but mucosal endocrine cells appear to be under proliferative stimulation; in H. pylori-positive patients there are changes in mucosal inflammation and atrophy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anti-Ulcer Agents / therapeutic use*
  • Atrophy
  • Enteroendocrine Cells / pathology
  • Female
  • Gastric Acid / metabolism
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / pathology
  • Gastroesophageal Reflux / complications
  • Gastroesophageal Reflux / drug therapy*
  • Gastroesophageal Reflux / surgery
  • Helicobacter Infections / complications
  • Helicobacter Infections / drug therapy
  • Helicobacter pylori
  • Humans
  • Male
  • Middle Aged
  • Omeprazole / therapeutic use*
  • Severity of Illness Index


  • Anti-Ulcer Agents
  • Omeprazole