Occurrence and influencing factors of PD-1/PD-L1 inhibitor-related liver injury in patients with extrahepatic primary carcinoma
10.3760/cma.j.cn114015-20220608-00496
- VernacularTitle:原发肝外肿瘤患者PD-1/PD-L1抑制剂相关肝损伤的发生情况及影响因素分析
- Author:
Ying JIANG
1
;
Ningping ZHANG
;
Qing XU
;
Qianzhou LYU
;
Hong GAO
;
Tianshu LIU
;
Xiaoyu LI
Author Information
1. 复旦大学附属中山医院药剂科，上海 200032
- Publication Type:Journal Article
- Keywords:
Immune checkpoint inhibitors;
Chemical and drug induced liver injury;
Carcinoma
- From:
Adverse Drug Reactions Journal
2023;25(2):76-82
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the occurrence of programmed cell death 1 receptor (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor-related liver injury and the influencing factors in patients with extrahepatic primary tumors.Methods:The electronic medical records of patients with extrahepatic primary tumors who were treated with PD-1/PD-L1 inhibitors in Zhongshan Hospital, Fudan University from January to July 2021 were collected and retrospectively analyzed. Patients with PD-1/PD-L1 inhibitor-related liver injury were screened out, and the occurrence time, clinical type, and severity of liver injury were statistically recorded and analyzed. Patients were divided into liver injury group and non-liver injury group according to whether liver injury occurred. Clinical characteristics including age, gender, type of primary tumor, underlying disease, liver metastasis, regimen of PD-1/PD-L1 inhibitor therapy, combined medication, and baseline liver and renal function were compared between the 2 groups. The influencing factors of liver injury were analyzed by multivariate logistic regression method, and the odds ratio ( OR) and 95% confidence interval ( CI) were calculated. Results:A total of 386 patients were included in the analysis and 29 patients had PD-1/PD-L1 inhibitor-related liver injury, with an incidence of 7.5%. Of the 29 patients, 25 were male and 4 were female, aged from 19 to 90 years. PD-1/PD-L1 inhibitors used were sintilimab, nivolumab, teriprizumab, pembrolizumab, tislelizumab, atezolizumab, camrelizumab, and durvalumab in 7, 5, 5, 4, 3, 3, 1, and 1 patient, respectively. The median time from drug use to the occurrence of liver injury was 44 (24, 112) days. The liver injury were typed as hepatocellular injury in 8 patients, cholestatic liver injury in 17 patients, and mixed type in 4 patients, and the severity was grade 1 in 19 patients, grade 2 in 7 patients, and grade 3 in 3 patients. After diagnosis of liver injury, all 29 patients were given symptomatic treatments, of which 24 patients discontinued PD-1/PD-L1 inhibitors; 21 patients had recovered liver function after 6-71 days, and 8 developed chronic hepatitis. Multivariate logistic regression analysis showed that hepatitis virus infection ( OR=5.749, 95 %CI: 1.337-24.719, P=0.019), hypertension ( OR=5.345, 95 %CI: 2.034-14.047, P=0.001), and baseline alkaline phosphatase (ALP) ≥125 U/L ( OR=4.651, 95 %CI: 1.728-12.521, P=0.002) were independent risk factors for PD-1/PD-L1 inhibitor-related liver injury. Conclusions:Liver injury is a common adverse reaction of PD-1/PD-L1 inhibitors, and cholestatic liver injury is the most common clinical type. Patients with hepatitis virus infection, hypertension, and elevated baseline ALP are at high risk for developing PD-1/PD-L1 inhibitor-associated liver injury.
