免疫检查点抑制剂诱导的药物性肝损伤临床和病理学特征

摘要/Abstract

摘要： 目的探讨免疫检查点抑制剂(ICIs)诱导的药物性肝损伤(DILI)患者临床和病理学特征情况。方法选取进行ICIs治疗的恶性肿瘤患者85例,包括非小细胞肺癌38例、肾细胞癌21例、尿路上皮癌14例及恶性黑色素瘤12例,将ICIs治疗后出现的DILI分为肝细胞损伤型、胆汁淤积型和混合型,比较DILI、非DILI以及各临床分型DILI患者临床资料,利用肝活检分析不同临床分型DILI患者病理学表现。结果 DILI患者高脂血症发生率、ICIs治疗期,血清ALT、AST、ALP、TBil水平分别为9例(16.7%)、120(80,140)d、162(78,204)U/L、155(70,195)U/L、208(122,310)U/L、78.6(55.0,93.8)μmol/L,显著高于非DILI患者[分别为1例(3.2%)、85(62,114)d、54(38,68)U/L、55(35,63)U/L、120(86,160)U/L、24.5(17.0,42.6)μmol/L,P<0.05],而疾病控制率显著低于非DILI患者[40.7%比64.5%,P<0.05]。经保肝处理,不同临床分型DILI患者血生化指标均得以恢复,其中肝细胞损伤型以ALT、AST改善更为显著,胆汁淤积型和混合型以ALP、TBil改善更为显著。部分DILI患者进行肝活检,各临床分型DILI患者中央区坏死、点状坏死、界面性肝炎、汇管区炎症及胆管反应等病理学表现差异具有统计学意义(P<0.05),其中肝细胞损伤型以中央区坏死、点状坏死多见,而胆汁淤积型、混合型以界面性肝炎、汇管区炎症和胆管反应多见。结论 ICIs-DILI患者中以肝细胞损伤型占主导,但胆汁淤积型和混合型具有独特的生化与组织学模式。

关键词: 免疫检查点抑制剂, 药物性肝损伤, 肝细胞损伤型

Abstract: Objective To investigate the clinical and pathological features of drug-induced liver injury (DILI) induced by immune checkpoint inhibitors (ICIs). Methods A total of 85 cancer patients treated with ICIs were selected, including 38 cases of non-small cell lung cancer, 21 cases of renal cell carcinoma, 14 cases of urothelial carcinoma, and 12 cases of malignant melanoma. DILI occurring after ICIs treatment was classified into hepatocellular injury type, cholestatic type, and mixed type. Clinical data were compared between DILI and non-DILI patients, as well as among different clinical subtypes of DILI. Liver biopsies were analyzed to compare pathological manifestations across subtypes. Results In the DILI group, the prevalence of hyperlipidemia, duration of ICI treatment, and levels of ALT, AST, ALP, and TBil were 9 cases (16.7%), 120 (80, 140) d, 162 (78, 204) U/L, 155 (70, 195) U/L, 208 (122, 310) U/L, and 78.6 (55.0, 93.8) μmol/L, respectively, which were significantly higher than those in the non-DILI group [1 case (3.2%), 85 (62, 114) d, 54 (38, 68) U/L, 55 (35, 63) U/L, 120 (86, 160) U/L, and 24.5 (17.0, 42.6) μmol/L, respectively; P<0.05].. Conversely, the disease control rate was significantly lower in DILI patients compared to non-DILI patients: 40.7% vs. 64.5% (P<0.05). After hepatoprotective treatment, blood biochemical indicators improved in all DILI subtypes: hepatocellular injury type showed more significant ALT and AST improvements, while cholestatic and mixed types demonstrated greater ALP and TBil improvements. Liver biopsies in some DILI patients revealed statistically significant differences in pathological features such as centrilobular necrosis, spotty necrosis, interface hepatitis, portal inflammation, and ductular reaction among subtypes (P<0.05). Hepatocellular injury type predominantly presented with central necrosis and spotty necrosis, whereas cholestatic and mixed types were characterized by interface hepatitis, portal inflammation, and bile duct reactions. Conclusion Hepatocellular injury type dominates among cases of ICI-induced DILI, but cholestatic and mixed types exhibit distinct biochemical and histological patterns.

Key words: Immune checkpoint inhibitors, Drug-induced liver injury, Hepatocellular injury type

李照强, 刘冬梅, 杜俊英. 免疫检查点抑制剂诱导的药物性肝损伤临床和病理学特征[J]. 肝脏, 2026, 31(8): 1174-1177.

Li Zhaoqiang, Liu Dongmei, Du Junying. Clinical and pathological features of immune checkpoint inhibitor-induced drug-induced liver injury[J]. Chinese Hepatolgy, 2026, 31(8): 1174-1177.

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