表皮生长因子受体酪氨酸激酶抑制剂致肝损伤的文献分析

Literature analysis of liver injury induced by EGFR-TKIs

目的分析探讨表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)致肝损伤的规律与特点,为临床合理用药提供参考。方法检索中国知网、万方数据库、维普网及Pub Med自建库至2022年1月的数据,对EGFR-TKIs致肝损伤的案例报道进行回顾性分析。结果共纳入40篇文献54例患者,其中男性23例,女性31例,年龄中位数64岁,以中国和日本居多(44例,占81.5%)。药物主要集中在吉非替尼(30例,占55.6%)、厄洛替尼(20例,占37.0%)。绝大多数发生在用药后3个月内(46例,占85.2%)。临床分型以肝细胞损伤型为主(39例,72.2%),轻中度居多(43例,79.6%)。肝损伤后EGFR-TKIs的再启用方面,降低给药剂量8例,更换药物20例。所有患者经临床处理后,好转或痊愈46例(占85.2%),死亡8例(占14.8%)。结论临床应警惕EGFR-TKIs肝损伤的发生,特别是对于有多种危险因素(如大剂量、联合使用质子泵抑制剂、病毒性肝炎或肺癌肝转移等)的患者,加强肝功能监测,一旦肝损伤发生,在护肝的同时应积极尝试可行的EGFR-TKIs再启用策略(如脱敏给药法,更换药物),以实现EGFR-TKIs临床应用最大化。

AIM To analyze and explore the law and characteristics of liver injury caused by epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),so as to provide reference for clinical rational drug use.METHODS The data from the establishment of CNKI,Wanfang database,VIP and Pub Med to January 2022 were retrieved,and the case reports of liver injury caused by EGFR-TKIs were analyzed retrospectively.RESULTS A total of 54 patients in 40 literatures were included,including 23 males and 31 females,with a median age of 64 years.Most of them were in China and Japan(44 cases,81.5%).The drugs were mainly gefitinib(30 cases,55.6%) and erlotinib(20 cases,37.0%).Most of them occurred within 3 months after treatment(46 cases,85.2%).The clinical classification was mainly hepatocyte injury(39 cases,72.2%),with majority being mild to moderate(43 cases,79.6%).In terms of reactivation of EGFR-TKIs after liver injury,the dosage was reduced in 8 cases and drugs were changed in 20 cases.After clinical treatment,46 cases(85.2%) improved or recovered and 8 cases(14.8%) died.CONCLUSION The occurrence of EGFR-TKIs liver injury should be alert,especially for patients with multiple risk factors(such as high dose,combined proton pump inhibitors,viral hepatitis or liver metastasis of lung cancer,etc.).The monitoring of liver function should be strengthened.Once liver damage occurs,while protecting liver function,feasible strategies for reactivation of EGFR-TKIs(such as desensitization administration and drug replacement) should be activity attempted to maximize the clinical application of EGFR-TKIs.