Proton Pump Inhibitors and Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B or C

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 pair 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 PPIs 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 HCC in the 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 dose-dependent effect of PPI use and HCC risk. Subgroup analysis also confirmed PPI use was not correlated to an increased HCC risk. Conclusions Based on a retrospective, nationwide population-based cohort study in 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. This article is protected by copyright. All rights reserved.