中国癌症杂志2025，Vol.35Issue(12)：1099-1107,9.DOI:10.19401/j.cnki.1007-3639.2025.12.002
消化道恶性肿瘤免疫检查点抑制剂相关严重肝损伤的临床特征及预后分析
Clinical characteristics and prognosis of severe immune checkpoint inhibitors-related liver injury in gastrointestinal malignancies
摘要
Abstract
Background and purpose:Immune checkpoint inhibitor(ICI)has demonstrated significant efficacy in the treatment of malignant tumors.However,the immune-related adverse event(irAE)may limit clinical benefits in some patients.Immune checkpoint inhibitor-related liver injury(ICILI)is a common irAE and can lead to treatment discontinuation and poor prognosis in severe cases.In China,research on the clinical characteristics and prognostic factors of severe ICILI remains limited.Therefore,this study aimed to investigate the clinical features and prognostic influencing factors of severe liver injury caused by ICI.Methods:Patients with digestive system malignancies who received ICI treatment at Zhongshan Hospital,Fudan University between January 2019 and June 2023 were retrospectively enrolled.ICILI severity was graded according to the Common Terminology Criteria for Adverse Events(CTCAE)version 5.0.Clinical features were compared across different grades of ICILI,and logistic regression analysis was used to identify risk factors for severe ICILI.Receiver operating characteristic(ROC)curve analysis was used to evaluate predictors of poor prognosis.This study was approved by the Ethics Committee of Zhongshan Hospital Affliated to Fudan University(Approval Number:B2025-334R).Results:Among the 1 421 patients,327(23.01%)developed ICILI of any grade,including 69(4.86%)with grade 3/4 ICILI.Multivariate analysis identified liver metastasis(OR=3.477,95%CI:1.883-6.419,P＜0.001),combined therapy with tyrosine kinase inhibitor(TKI)(OR=2.710,95%CI:1.298-5.657,P=0.008),and elevated baseline gamma-glutamyl transferase(GGT)(OR=1.003,95%CI:1.000-1.006,P=0.047)as independent risk factors for grade 3/4 ICILI.Among patients with grade 3/4 ICILI,40 showed clinical improvement while 14 did not.ROC curve analysis indicated that the Model for End-Stage Liver Disease(MELD)score predicted poor prognosis with an area under the curve(AUC)of 0.876(95%CI:0.761-0.991,P＜0.001).The optimal cutoff value was 11.5,yielding a sensitivity of 85.71%and a specificity of 86.05%.Conclusion:The incidence of grade 3/4 ICILI in patients receiving ICI for digestive system malignancies was 4.86%.Patients with baseline liver metastasis,combined TKI therapy,or elevated initial GGT levels are at higher risk of severe ICILI.The MELD score demonstrates good predictive performance for poor prognosis.关键词
免疫检查点抑制剂/药物性肝损伤/临床特征/预后分析Key words
Immune checkpoint inhibitor/Drug-induced liver injury/Clinical characteristics/Prognostic analysis分类
医药卫生引用本文复制引用
MAO Tianxiao,JIANG Ying,WANG Chunhui,XU Bei,LI Xiaoyu..消化道恶性肿瘤免疫检查点抑制剂相关严重肝损伤的临床特征及预后分析[J].中国癌症杂志,2025,35(12):1099-1107,9.基金项目
"2024耀动神州-药学科研能力建设基金"(Z04J2023E095) （Z04J2023E095）
上海市抗癌协会"雏鹰"计划(SACA-CY24C13). 2024 Shining Across China-Pharmaceutical Research Capacity Building Fund(Z04J2023E095) （SACA-CY24C13）
Shanghai Anticancer Association EYAS Project(SACA-CY24C13). （SACA-CY24C13）
