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. 2023 Aug 25:14:1244400.
doi: 10.3389/fphar.2023.1244400. eCollection 2023.

Long-term proton pump inhibitors use and its association with premalignant gastric lesions: a systematic review and meta-analysis

Zeyi Zheng  1 , Ziyu Lu  2 , Yani Song  3
Affiliations

Long-term proton pump inhibitors use and its association with premalignant gastric lesions: a systematic review and meta-analysis

Zeyi Zheng et al. Front Pharmacol. .

Abstract

Background: Long-term maintenance therapy with proton pump inhibitors (PPIs) is a common treatment strategy for acid-related gastrointestinal diseases. However, concerns have been raised about the potential increased risk of gastric cancer and related precancerous lesions with long-term PPI use. This systematic review and meta-analysis aimed to evaluate this potential risk. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before 1 March 2023, with no language restrictions. The primary endpoint was the occurrence and progression of gastric mucosal atrophy, intestinal metaplasia, Enterochromaffin-like (ECL) cell hyperplasia, gastric polyps, and gastric cancer during the trial and follow-up. Data were analysed using a random effects model. Results: Of the 4,868 identified studies, 10 met the inclusion criteria and were included in our analysis, comprising 27,283 participants. Compared with other treatments, PPI maintenance therapy for more than 6 months was associated with an increased risk of ECL cell hyperplasia (OR 3.01; 95% CI 1.29 to 7.04; p = 0.01). However, no significant increase was found in the risk of gastric mucosal atrophy (OR 1.01; 95% CI 0.55 to 1.85; p = 0.97), intestinal metaplasia (OR 1.14; 95% CI 0.49 to 2.68; p = 0.76), gastric polyps (OR 1.13; 95% CI 0.68 to 1.89; p = 0.64), or gastric cancer (OR 1.06; 95% CI 0.79 to 1.43; p = 0.71). Conclusion: This systematic review and meta-analysis does not support an increased risk of gastric cancer or related precancerous lesions with long-term PPI maintenance therapy. However, long-term PPI use should be monitored for potential complications such as ECL cell hyperplasia. Further studies are needed to confirm these findings and evaluate the safety of PPI maintenance therapy for acid-related gastrointestinal diseases. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, Identifier: PROSPERO (CRD42022379692).

Keywords: enterochromaffin-like cell; gastric cancer; gastric mucosal atrophy; gastric polyps; intestinal metaplasia; meta-analysis; proton pump inhibitors.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
PRISMA flowchart illustrating the process of screening and selection of studies.
FIGURE 2
FIGURE 2
Risk of bias graph.
FIGURE 3
FIGURE 3
Risk of bias summary.
FIGURE 4
FIGURE 4
Forest plots of odds ratios for atrophy in participants receiving proton pump inhibitors compared with subjects not receiving proton pump inhibitors.
FIGURE 5
FIGURE 5
Forest plots of odds ratios for intestinal metaplasia in participants receiving proton pump inhibitors compared with subjects not receiving proton pump inhibitors.
FIGURE 6
FIGURE 6
Forest plots of odds ratios for ECL cell hyperplastic in participants receiving proton pump inhibitors compared with subjects not receiving proton pump inhibitors.
FIGURE 7
FIGURE 7
Forest plots of the odds of ECL cell proliferation in participants who received proton pump inhibitors compared to those who did not receive proton pump inhibitors by different observation duration.
FIGURE 8
FIGURE 8
Forest plots of the odds of ECL cell proliferation in participants who received proton pump inhibitors compared to those who did not receive proton pump inhibitors by using different types of PPIs.
FIGURE 9
FIGURE 9
Forest plots of odds ratios for gastric polyps in participants receiving proton pump inhibitors compared with subjects not receiving proton pump inhibitors.
FIGURE 10
FIGURE 10
Forest plots of odds ratios for gastric cancer in participants receiving proton pump inhibitors compared with subjects not receiving proton pump inhibitors.
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