Liver injury related to vascular endothelial growth factor tyrosine kinase inhibitors: a pharmacovigilance analysis of the USA FDA adverse event reporting system (FAERS) database

While vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR-TKIs) are known to cause adverse events like cardiotoxicity and haematotoxicity, their impact on liver injury remains understudied. This study evaluates the association between VEGFR-TKIs and liver injury using data from the FDA Adverse Event Reporting System (FAERS) database from 2006 to 2024. Nine VEGFR-TKIs (Axitinib, Vandetanib, Cabozantinib, Lenvatinib, Pazopanib, Ponatinib, Regorafenib, Sunitinib, Sorafenib) were analyzed. Disproportionality and Bayesian analyses identified cases of VEGFR-TKI-induced liver injury, assessing onset time, mortality, and hospitalization rates. 8,619 cases of liver injury were identified. Pazopanib had the highest association with liver injury (reporting odds ratio 3.9). The median onset of liver injury was 21 days. Mortality was 28.5%, with Sorafenib linked to the highest mortality (48.6%). Lenvatinib had the highest hospitalization rate (56%). VEGFR-TKIs are associated with liver injury. Close monitoring is required to mitigate the risks of hospitalization and early mortality during treatment.

尽管血管内皮生长因子酪氨酸激酶抑制剂（vascular endothelial growth factor tyrosine kinase inhibitors，VEGFR-TKIs）已知可引发心脏毒性、血液毒性等不良反应，但其对肝损伤的影响仍未被充分研究。本研究采用2006年至2024年美国食品药品监督管理局不良事件报告系统（FDA Adverse Event Reporting System，FAERS）数据库的数据，评估VEGFR-TKIs与肝损伤之间的关联。本研究共纳入9种VEGFR-TKIs进行分析，分别为阿昔替尼、凡德他尼、卡博替尼、仑伐替尼、帕唑帕尼、普纳替尼、瑞戈非尼、舒尼替尼与索拉非尼。通过比例失衡分析与贝叶斯分析，本研究识别出VEGFR-TKIs诱导的肝损伤病例，并对其发病时间、死亡率及住院率进行了评估。最终共识别出8619例肝损伤相关病例。其中帕唑帕尼与肝损伤的关联强度最高，报告比值比（reporting odds ratio，ROR）为3.9。肝损伤的中位发病时间为21天。整体肝损伤相关死亡率为28.5%，其中索拉非尼相关的死亡率最高，达48.6%。仑伐替尼的住院率最高，为56%。本研究证实VEGFR-TKIs与肝损伤存在显著关联，临床治疗过程中需加强监测，以降低住院及早期死亡风险。