Background: Acid-suppressive agents (ASAs), which are mostly used in patients with upper gastrointestinal diseases (UGIDs), may influence the risk of hepatocellular carcinoma (HCC). Methods: A population-based retrospective cohort study was conducted. Patients with UGID who used ASAs and those who did not receive ASAs were identified. Patients without UGIDs were randomly selected and matched (comparison group). All groups were followed up for 6 years. A Cox proportional hazard model was used to estimate the risk of HCC among the different groups. Results: Patients with UGID who used ASAs had a significantly elevated HCC risk (adjusted hazard ratio [HR] 1.53; 95% confidence interval [CI], 1.32-1.76] compared to those who did not use ASAs. Patients with UGID who used more than 540 defined daily doses of ASAs had a significantly higher risk of HCC (adjusted HR 2.04; 95% CI, 1.62-2.58). Moreover, the dose effect on HCC risk exhibited a significant increasing trend (P <.01). Furthermore, patients with UGID who did not use ASAs had a significantly elevated HCC risk (adjusted HR 1.94; 95% CI, 1.59-2.36) compared to the comparison group. Conclusion: The use of ASAs increased the risk of HCC in patients with UGIDs, and the effect of ASAs was dose dependent. In addition, UGIDs alone increased the risk of HCC.
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