Gastric acid secretion therapy: long-term effects on gastric mucosa and polyp formation

Proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are widely used for the management of acid-related disorders. Characteristic gastric mucosal changes have gained clinical attention owing to their widespread and prolonged use.

We outline the pharmacological differences between PPIs and P-CABs and we summarize their endoscopic and histological features. Hypergastrinemia is highlighted as a central mediator, interacting with factors including Helicobacter pylori infection, atrophic gastritis, age, and sex. Evidence from randomized and observational studies, case series, and mechanistic investigations has been integrated to provide an overview of the long-term effects of these therapies.

Most reported mucosal alterations, including fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cracked or cobblestone-like mucosa, black spots, gastric mucosal redness, white spots, and web-like mucus, are considered benign. Although endoscopic surveillance is not currently supported by evidence, awareness of these findings may be useful in patients receiving therapy for several decades. Endoscopic features,-associated with hypergastrinemia and parietal- or enterochromaffin-like cell proliferation, may serve as tools to guide individualized prescribing and deprescribing strategies. Further research should include decade-long cohort studies, studies comparing PPIs and P-CABs, and trials evaluating on-demand and continuous regimens to optimize long-term safety.