Using Proton Pump Inhibitors Increases the Risk of Hepato-Biliary-Pancreatic Cancer. A Systematic Review and Meta-Analysis

Background: More and more studies are focusing on the adverse effects and damage caused by PPI abuse, we carried out a systematic review and meta-analysis for assessing whether the proton pump inhibitor (PPI) leads to liver-biliary-pancreatic cancer. Methods: : PubMed, EMBASE and Web of Science were searched until July 1, 2022, 24 studies (16 case-control and 8 cohort studies; 274, 0958 individuals) included in this study. Pooled Odd Ratios (ORs) were used for random effect models. Sensitivity analysis and dose-response analysis, subgroup analysis were all conducted. Results: : The aggregate OR of the meta-analysis was 1.69 (95% confidence interval (CI): 1.23-2.22, P = 0.01) and heterogeneity ( I 2 = 98.9%, P < 0.001) was substantial. According to stratified subgroup analyses, the incidence of hepato-biliary-pancreatic cancer was associated, expect for study design, study quality and region. Risk of hepato-biliary-pancreatic cancer is highest when people is treated with normal doses of PPI. The risks decrease and become insignificant when the cumulative defined daily dose (cDDD) increases. Conclusion: The use of PPI may be associated with an increased risk of hepato-biliary-pancreatic cancer. Hence, caution is needed when using PPIs among patients with a high risk of hepato-biliary-pancreatic cancer.