Background and Objectives: Mounting evidence demonstrates that proton pump inhibitors (PPIs) are associated with a number of adverse effects. However, the literatures about hepatotoxicity-related adverse effects (HRAEs) of PPIs are mostly case reports and a few clinical studies.Methods: We evaluated the association between PPIs and HAREs using the reporting odd ratio (ROR) for mining the adverse event report signals in the FDA Adverse Event Reporting System (FAERS) database.Results: There were 23,825 reports of PPIs as primary suspect drug or second suspect drug, of which 3,253 reports were HRAEs. The top five HRAE signals caused by PPIs were hepatitis cholestatic, cholestasis, fulminant hepatitis, subacute hepatic failure, and acute hepatitis. We also summarized the signals of the HRAEs caused by each PPI. The simultaneous signals were cholestasis and hepatitis cholestatic. For the cholestasis signal, esomeprazole showed an ROR of 21.556 (95% CI 17.592–26.413); pantoprazole showed the highest ROR of 22.611 (95% CI 17.794–28.733) in the hepatic cholestatic signal; lansoprazole was the only PPI with expression in the coma hepatic signal, with an ROR of 10.424 (95% CI 3.340–32.532). By analyzing the reports of pantoprazole-induced hepatic encephalopathy, we found that patients aged over 65 years and males reported the highest rate. And from the combination of drugs and indications of drugs, no significant results were obtained.Conclusions: The RORs of signals of “cholestasis” were generally higher than those of “hepatocellular injury.” And the signals about “cholestasis” in HRAE caused by PPIs are more reported.

What is known and Objective. Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors (ALK TKIs) are standard first‐line therapy for non‐small cell lung cancer patients with ALK rearrangement. Although some cases of hepatotoxicity related to these drugs have been reported, there is still a lack of investigation on severe hepatotoxicity, such as hepatic failure, with ALK TKIs. Methods We evaluated ALK TKI (crizotinib, alectinib, brigatinib, ceritinib and lorlatinib)‐induced hepatic failure events (AIHFEs), by using the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network method for mining the adverse event report signals in the FDA Adverse Event Reporting System (FAERS) database from Jan 2013 to Dec 2019. Results and Discussion The AIHFEs of “Hepatic failure,” “hepatitis fulminant” and “hepatic necrosis” were defined as exposure event signals caused by ALK TKIs. The RORs of “Hepatic failure” were 4.95 (2.36–10.42) in alectinib, 3.77 (1.69–8.40) in ceritinib and 2.45 (1.60–3.76) in crizotinib, respectively. The ROR of “hepatitis fulminant” was 7.86 (3.52–17.54) in crizotinib. The Information Component value of “hepatic necrosis” was 1.97 (0.15) in alectinib. In reports of exposure‐event signals, the clinical outcome of eventual death was common and could occur within 3 months. In the reports of “hepatic failure,” there was no significant difference in the number of reports between men and women [OR=1.86 (0.94–3.67), p = 0.09]. What is new and Conclusions. By mining the adverse event report signals in the FAERS database, we found the exposure event signals of AIHFEs in ALK TKIs were “hepatic failure,” “hepatitis fulminant” and “hepatic necrosis”. AIHFEs were more likely to appear in the reports of ceritinib, crizotinib and alectinib.