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首页> 外文期刊>Journal of immunotherapy >Analysis of Risk Factors for Hepatotoxicity Induced by Immune Checkpoint Inhibitors
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Analysis of Risk Factors for Hepatotoxicity Induced by Immune Checkpoint Inhibitors

机译：免疫检查点抑制剂诱导肝毒性危险因素分析

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Although hepatotoxicity induced by immune checkpoint inhibitors (ICPIs) can cause severe clinical complications, the risk factors associated with hepatotoxicity have rarely been investigated. The purpose of this study was to determine the potential risk factors for the incidence of hepatotoxicity and for time to ICPI-induced hepatotoxicity. Patients who received ICPIs (atezolizumab, nivolumab, pembrolizumab, and ipilimumab) were included in this retrospective 2-center study. Collected data included sex, age, body weight, body surface area, Eastern Cooperative Oncology Group performance status, underlying disease, liver metastasis, programmed cell death ligand-1 expression, interval from previous chemotherapy, and concomitant drug use. Among the 194 patients, patients who experienced hepatotoxicity after ICPI administration was 64.4% (n=125) in all grade and 10.8% (n=21) in grade III or higher. Multivariate analysis showed that patients aged 30-50 and 50-70 years had increased risks of hepatotoxicity by 4.9-fold (95% confidence interval, 1.3-18.0) and 2.7-fold (95% confidence interval, 1.3-5.5), respectively, compared with those older than 70 years. The use of acetaminophen increased the occurrence of hepatotoxicity by 2.1 times; the attributable risk was 53.2%. Male patients and patients younger than 65 years had around 1.5-fold increased hazard of time to reach hepatotoxicity. Patients treated with 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors had a 4.7-fold higher risk of grade III-IV hepatotoxicity compared with those without HMG-CoA reductase inhibitors; the attributable risk was 78.8%. In conclusion, close monitoring of liver function is recommended, especially in male patients, patients younger than 65 years old, and when there is concomitant use of hepatotoxic drugs including acetaminophen and HMG-CoA reductase inhibitors.
机译：虽然免疫检查点抑制剂（ICPI）引起的肝毒性可导致严重的临床并发症，但与肝毒性相关的风险因素很少被研究。本研究的目的是确定肝毒性发生率和ICPI诱导肝毒性时间的潜在风险因素。接受ICPIs（阿替唑单抗、nivolumab、彭布罗利单抗和伊普利单抗）的患者被纳入这项回顾性双中心研究。收集的数据包括性别、年龄、体重、体表面积、东部肿瘤合作组的表现状态、基础疾病、肝转移、程序性细胞死亡配体-1表达、与先前化疗的间隔时间以及伴随用药。在194名患者中，ICPI给药后出现肝毒性的患者在所有级别中为64.4%（n=125），在III级或更高级别中为10.8%（n=21）。多变量分析显示，与70岁以上的患者相比，30-50岁和50-70岁的患者肝毒性风险分别增加了4.9倍（95%可信区间1.3-18.0）和2.7倍（95%可信区间1.3-5.5）。对乙酰氨基酚的使用使肝毒性的发生率增加了2.1倍；归因风险为53.2%。男性患者和65岁以下患者发生肝毒性的时间风险增加约1.5倍。与未使用HMG-CoA还原酶抑制剂的患者相比，使用3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂的患者发生III-IV级肝毒性的风险高4.7倍；归因风险为78.8%。总之，建议密切监测肝功能，尤其是男性患者、65岁以下的患者，以及同时使用对乙酰氨基酚和HMG-CoA还原酶抑制剂等肝毒性药物时。

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