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

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-Q_1–4] 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 (P_total 0.007, P_trend 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 (P_total 0.004, P_trend 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 (P_total 0.288, P_trend 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.