Association between proton pump inhibitors and the risk of hepatocellular carcinoma

Summary Background Proton pump inhibitor ( PPI ) use has been reported to be associated with liver damage and might possibly be carcinogenic. Aims We examined whether long‐term PPI use increases the risk of hepatocellular carcinoma ( HCC ) in patients without viral hepatitis B or C. Methods We conducted a nested case‐control study in a cohort of patients without viral hepatitis in Taiwan from 2000 to 2013. In total, 29 473 HCC cases and 294 508 matched controls were included. Moreover, we identified prescriptions for PPI and durations between the PPI index date and cancer diagnosis date (or the corresponding date in controls). Results The adjusted odds ratio ( AOR ) for HCC associated with PPI use was 2.86 (95% confidence interval [ CI ], 2.69‐3.04). Considering the use of PPI s determined according to cumulative defined daily dose ( cDDD ) subgroups, a dose‐response effect was observed in patients exposed to 29‐180, 181‐240, 241‐300, and 300+ cDDD s of PPI s. The AOR s were 2.74 (95% CI , 2.57‐2.93), 2.98 (95% CI , 2.50‐3.56), 3.23 (95% CI , 2.59‐4.02), and 3.43 (95% CI , 2.94‐4.00) in the 29‐180, 181‐240, 241‐300, and 300+ cDDD groups, respectively, compared with the 0‐28 cDDD group. A sensitivity analysis revealed a consistent association between PPI use and the risk of HCC in subpopulations stratified by risk factors associated with HCC. Conclusions This observational study demonstrated that PPI s might increase the risk of HCC .