Zeng Yifan, Dai Ying, Zhou Ziye, Yu Xuben, Shi Dawei
Computer Technology and Information Centre, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Pharmacy, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Med (Lausanne). 2021 Nov 15;8:648164. doi: 10.3389/fmed.2021.648164. eCollection 2021.
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. 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. 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. 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.
越来越多的证据表明，质子泵抑制剂（PPIs）与多种不良反应相关。然而，关于PPIs肝毒性相关不良反应（HRAEs）的文献大多为病例报告，仅有少数临床研究。我们使用报告比值比（ROR）评估PPIs与HRAEs之间的关联，以挖掘美国食品药品监督管理局不良事件报告系统（FAERS）数据库中的不良事件报告信号。有23,825份报告将PPIs列为主要可疑药物或次要可疑药物，其中3,253份报告为HRAEs。由PPIs引起的前五大HRAE信号为胆汁淤积性肝炎、胆汁淤积、暴发性肝炎、亚急性肝衰竭和急性肝炎。我们还总结了每种PPI引起的HRAEs信号。同时出现的信号为胆汁淤积和胆汁淤积性肝炎。对于胆汁淤积信号，埃索美拉唑的ROR为21.556（95%可信区间17.592 - 26.413）；泮托拉唑在肝内胆汁淤积信号中显示出最高的ROR，为22.611（95%可信区间17.794 - 28.733）；兰索拉唑是唯一在肝昏迷信号中有表现的PPI，ROR为10.424（95%可信区间3.340 - 32.532）。通过分析泮托拉唑所致肝性脑病的报告，我们发现65岁以上患者和男性的报告率最高。并且从药物组合和药物适应证方面未得出显著结果。“胆汁淤积”信号的ROR通常高于“肝细胞损伤”信号。而且PPIs引起的HRAEs中关于“胆汁淤积”的信号报告更多。
