Objective To systematically review the risk of hepatotoxicity caused by vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) in clinical practice.
Methods PubMed, Embase, CENTRAL, CNKI, WanFang Data and SinoMed databases were electronically searched to collect randomized controlled trials (RCTs) of hepatotoxicity caused by VEGFR-TKI from inception to February 28, 2024. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of the included studies. Network Meta-analysis was then performed by Stata 15.0 software.
Results A total of 32 RCTs were included, involving 9 kinds of VEGFR-TKI and 12 949 patients. The results of network Meta-analysis showed that compared with placebo, except for a non-significant increase in the risk of alanine aminotransferase (ALT) elevation due to anlotinib, a non-significant increase in the risk of aspartate aminotransferase (AST) elevation due to anlotinib and vandetanib, and a non-significant increase in the risk of total bilirubin (TBIL) elevation due to anlotinib, vandetanib, sorafenib, and lenvatinib, the risks of ALT, AST, and TBIL elevation due to the rest of the VEGFR-TKI were all significantly increased; Pazopanib and apatinib had remarkable increase in the risk of high-grade ALT elevation. Pazopanib, apatinib, sunitinib, sorafenib, and cabozantinib had a remarkable increase in the risk of high-grade AST elevation. Regorafenib had a remarkable increase in the risk of high-grade TBIL elevation.
Conclusion VEGFR-TKI can increase the risk of hepatotoxicity in patients, the risks of elevated indicators caused by different VEGFR-TKI are not the same.
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