# Long-Term Proton Pump Inhibitor Therapy and Risk of Gastric Atrophy and Precancerous Mucosal Changes: A Systematic Review

## TL;DR

This study reviews whether long-term use of acid-suppressing drugs increases the risk of stomach changes linked to cancer, finding mixed results influenced by infection status.

## Contribution

A systematic review of clinical trials clarifying the inconsistent effects of long-term proton pump inhibitors on gastric atrophy and precancerous changes.

## Key findings

- Long-term proton pump inhibitor therapy alone did not consistently accelerate gastric atrophy or intestinal metaplasia.
- H. pylori eradication was associated with stability or regression of mucosal changes in some studies.
- Evidence highlights the importance of managing H. pylori infection in patients on prolonged acid suppression.

## Abstract

This systematic review evaluated the association between long-term use of proton pump inhibitors (acid-suppressing medications) and the development of gastric atrophy and related precancerous mucosal changes. Six clinical trials involving a total of more than 1,100 patients with acid-peptic disorders were analyzed, encompassing diverse study designs, follow-up durations ranging from two to five years, and variable Helicobacter pylori infection status. Across these studies, long-term proton pump inhibitor therapy alone did not consistently accelerate the progression of gastric atrophy or intestinal metaplasia. Three trials demonstrated stability or regression of mucosal changes following eradication of H. pylori, while two reported progression of corpus atrophy or metaplasia in patients with persistent infection; one study found minimal overall histological change regardless of therapy. Some studies noted hypergastrinemia and corpus atrophy during prolonged treatment, but these findings were inconsistent and often influenced by baseline histology and geographic variation. Collectively, the evidence underscores the importance of assessing and managing H. pylori infection in patients requiring prolonged acid suppression. The available evidence is limited by the small number of trials, modest sample sizes in some studies, and reliance on older data, highlighting the need for updated large-scale investigations.