Dose-dependent association of proton pump inhibitors use with gastric intestinal metaplasia among Helicobacter pylori-positive patients

United European Gastroenterol J. 2021 Apr;9(3):343-353. doi: 10.1177/2050640620951403. Epub 2021 Mar 18.

Abstract

Background: Gastric intestinal metaplasia is a pre-cancerous condition associated with multiple factors.

Objective: We evaluated whether cumulative proton pump inhibitor dose is associated with the diagnosis of gastric intestinal metaplasia while controlling for multiple variables.

Methods: We retrospectively identified patients who underwent upper endoscopy with gastric biopsy between 2005 and 2014. Covariate data retrieved included age, sex, ethnicity, smoking status, Helicobacter pylori status (based on clarithromycin-amoxicillin-proton pump inhibitor issued), cumulative proton pump inhibitor issued within 10 years (quartiles [PPI-Q1-4 ] of daily drug dose), anti-parietal cell antibodies, body mass index and comorbidity index.

Results: Of the 14,147 included patients (median age 63.4 years; women 54.4%; Helicobacter pylori-positive 29.0%), 1244 (8.8%) had gastric intestinal metaplasia. Increasing age, Helicobacter pylori infection, smoking, anti-parietal cell antibodies and proton pump inhibitor use were all associated with the diagnosis of gastric intestinal metaplasia. Upper quartiles of cumulative proton pump inhibitor doses (PPI-Q4 and PPI-Q3 vs. PPI-Q1 ) were associated with the diagnosis of gastric intestinal metaplasia: adjusted odds ratios 1.32 (95% confidence interval [CI] 1.111.57) and 1.27 (95% CI 1.07-1.52), respectively, for the whole cohort (Ptotal 0.007, Ptrend 0.013), 1.69 (95% CI 1.23-2.33) and 1.40 (95% CI 1.04-1.89), respectively, for Helicobacter pylori-positive patients (Ptotal 0.004, Ptrend 0.005) and 1.21 (95% CI 0.98-1.49) and 1.20 (95% CI 0.96-1.49), respectively, for Helicobacter pylori-negative patients (Ptotal 0.288, Ptrend 0.018). Upper quartiles of proton pump inhibitor dose were associated with a 5-10-fold increased risk of low-grade dysplasia.

Conclusions: Among Helicobacter pylori-positive patients, proton pump inhibitor use appears to be associated with a dose-dependent increased likelihood of gastric intestinal metaplasia.

Keywords: Helicobacter pylori; gastric intestinal metaplasia; proton pump inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Antibodies / analysis
  • Body Mass Index
  • Clarithromycin / therapeutic use
  • Confidence Intervals
  • Female
  • Gastroscopy
  • Helicobacter Infections / complications
  • Helicobacter Infections / drug therapy
  • Helicobacter pylori
  • Humans
  • Male
  • Metaplasia / chemically induced
  • Metaplasia / epidemiology
  • Middle Aged
  • Odds Ratio
  • Parietal Cells, Gastric / immunology
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / epidemiology
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects*
  • Retrospective Studies
  • Smoking / adverse effects
  • Stomach / pathology*

Substances

  • Anti-Bacterial Agents
  • Antibodies
  • Proton Pump Inhibitors
  • Amoxicillin
  • Clarithromycin