Researchers have hypothesized that the long-term use of proton pump inhibitors (PPIs) can increase the risk of developing cancer. However, the association between PPI use and hepatocellular carcinoma (HCC) risk is unclear. Using data from the Taiwan National Health Insurance Research Database for the period between 2003 and 2013, we identified 35,356 patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. One-to-one propensity score matching by gender, age, cohort entry year, comorbidity, and medication resulted in the inclusion of 7,492 pairs of patients (PPI users and non-PPI users) for analyses. We performed multivariate and stratified analysis using the Kaplan-Meier method and Cox proportional hazards models in order to estimate the association between PPI use and the risk of developing HCC. In the HBV cohort, 237 patients developed HCC during a median follow-up of 53 months. However, PPI use was not associated with an increased risk of developing HCC (adjusted hazard ratio [aHR], 1.25; 95% confidence interval [CI], 0.90-1.73; P = 0.18). In the HCV cohort, 211 patients developed HCC; but again, PPI use was not associated with an increase in the risk of developing HCC (aHR, 1.19; 95% CI, 0.88-1.61; P = 0.25). We observed no relationship between a dose-dependent effect of PPI use and HCC risk. Subgroup analysis also confirmed that PPI use was not correlated to an increased HCC risk. Conclusion: Based on a retrospective population-based cohort study throughout Taiwan, where the prescription of PPI is tightly regulated, PPI use is not associated with the risk of developing HCC among patients with chronic HBV or HCV infections.
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