Abstract
BACKGROUND AND AIM: Although gastric acid suppressants such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are considered safe, the consequences of hypochlorhydria and hypergastrinemia caused by chronic use are unclear. This study aimed to investigate the association between the chronic use of gastric acid suppressants and high-risk colorectal polyps, focusing on polyp size. METHODS: A population-based, nested case-control study was conducted using data from the Japanese Diagnosis Procedure Combination database between 2014 and 2019. Cumulative PPI or H2RA use prior to polypectomy was evaluated during the study period. Endoscopic polypectomy was categorized as polypectomy <2 cm, polypectomy ≥2 cm, and endoscopic submucosal dissection. Baseline characteristics were compared between the high-risk (≥2 cm polyps or polyps treated by endoscopic submucosal dissection) and low-risk (<2 cm polyps) endoscopic polypectomy groups. We calculated adjusted odds ratios (ORs) using multivariable logistic regression analysis. RESULTS: Of 27 694 patients who underwent endoscopic polypectomy, 2518 were treated with PPIs or H2RAs for >1 year prior to polypectomy. After adjusting for age, gender, and other confounders, a higher prevalence of high-risk colorectal polyps was noted with PPI (OR: 2.67; 95% confidence interval: 2.37-3.01) and H2RA (OR: 1.86; 95% confidence interval: 1.52-2.26) use. Longer PPI or H2RA use was associated with increased risks of high-risk colorectal polyps (P for trend <0.001). The highest OR (3.17) was observed among patients who received PPIs for ≥3 years. CONCLUSION: Chronic use of PPIs and H2RAs may be associated with high-risk colorectal polyps. Requirements for long-term gastric acid suppressant use should be reevaluated.