血管内皮生长因子受体酪氨酸激酶抑制剂肝毒性风险的网状Meta分析  

Risk of vascular endothelial growth factor receptor tyrosine kinase inhibitor induced hepatotoxicity:a network Meta-analysis

作　　者：金蜜 王陈翔[1] 叶中将 周子晔[3] JIN Mi;WANG Chenxiang;YE Zhongjiang;ZHOU Ziye(Department of Pharmacy,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang Province,China;Department of Pharmacy,the Fifth Affiliated Hospital of Wenzhou Medical University,Lishui 323000,Zhejiang Province,China;Clinical Research Center,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang Province,China)

机构地区：[1]温州医科大学附属第一医院药学部,浙江温州325000 [2]温州医科大学附属第五医院药学部,浙江丽水323000 [3]温州医科大学附属第一医院临床研究中心,浙江温州325000

出　　处：《药物流行病学杂志》2024年第12期1400-1413,共14页Chinese Journal of Pharmacoepidemiology

基　　金：温州市基础科研项目(Y2020184)。

摘　　要：目的系统评价血管内皮生长因子受体酪氨酸激酶抑制剂(VEGFR-TKI)肝毒性的风险。方法计算机检索PubMed、Embase、CENTRAL、CNKI、WanFang Data和SinoMed数据库,搜集VEGFR-TKI相关肝毒性的随机对照试验(RCT),检索时限均从建库至2024年2月28日。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险。采用Stata 15.0软件进行网状Meta分析。结果共纳入32个RCT,涉及9种VEGFR-TKI,包括12949例患者。网状Meta分析结果显示,与安慰剂相比,除安罗替尼致丙氨酸转氨酶(ALT)升高的风险未显著增加,安罗替尼、凡德他尼致天冬氨酸转氨酶(AST)升高的风险未显著增加,安罗替尼、凡德他尼、索拉非尼、仑伐替尼致总胆红素(TBIL)升高的风险未显著增加外,其余VEGFR-TKI致ALT、AST、TBIL升高的风险均有显著增加;与安慰剂相比,培唑帕尼、阿帕替尼致严重级别ALT升高的风险显著增加,培唑帕尼、阿帕替尼、舒尼替尼、索拉非尼、卡博替尼致严重级别AST升高的风险显著增加,瑞戈非尼致严重级别TBIL升高的风险显著增加。结论VEGFR-TKI可增加患者肝毒性的发生风险,不同VEGFR-TKI引发各指标升高的风险不同。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 12949 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 nonsignificant 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.

关 键 词：血管内皮生长因子受体酪氨酸激酶抑制剂 肝毒性 网状Meta分析 随机对照试验 

分 类 号：R969[医药卫生—药理学]