胆管损伤对PD-1抑制剂相关肝损伤临床病理特征影响分析

肝脏 ›› 2024, Vol. 29 ›› Issue (8): 965-970.

胆管损伤对PD-1抑制剂相关肝损伤临床病理特征影响分析

王艳, 刘立伟, 赵梦鱼, 陈炜, 赵新颜

100050 首都医科大学附属北京友谊医院肝病中心,国家消化系统疾病临床医学研究中心(王艳,赵梦鱼,赵新颜),消化内科(陈炜);100069 首都医科大学附属北京佑安医院肝病四科(刘立伟)

收稿日期:2024-05-16 出版日期:2024-08-31 发布日期:2024-09-30
通讯作者: 赵新颜, Email: zhao_xinyan@ccmu.edu.cn
基金资助:
科技创新2030“新一代人工智能”重大项目(2021ZD0113200);中国肝炎防治基金会王宝恩肝纤维化研究基金(WBE2020058)。

Analysis of the influence of bile duct injury of the Clinical and pathological characteristics of immune-mediated liver injury

WANG Yan¹, LIU Li-wei², ZHAO Meng-yu¹, CHEN Wei³, ZHAO Xin-yan¹

1. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases,Beijing 100050, China;
2. Fourth Department of Liver Disease, Beijing You’an Hospital, Capital Medical University, Beijing 100069, China;
3. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University,Beijing 100050, China

Received:2024-05-16 Online:2024-08-31 Published:2024-09-30
Contact: ZHAO Xin-yan, Email: zhao_xinyan@ccmu.edu.cn

摘要/Abstract

摘要： 目的探索PD-1抑制剂相关的免疫介导肝损伤临床特征。方法回顾分析2016年4月—2022年12月首都医科大学附属北京友谊医院住院的使用PD-1抑制剂且出现免疫介导肝损伤的恶性肿瘤患者。根据血清碱性磷酸酶水平,分为CTCAE 0级、1级、2级、3级。比较上述各组患者的临床表现、影像及病理表现。连续变量采用ANOVA检验或非参数检验,分类变量采用卡方检验,多重比较采用Bonferroni校正,P<0.05为差异有统计学意义。结果共纳入42例出现免疫介导肝损伤。根据CTCAE中ALP分级标准,有13例免疫介导肝损伤患者符合CTCAE 0级,14例1级,8例2级,7例3级。4个组间,肝损伤后CTCAE 3级患者血清胆红素明显高于CTCAE 0~2级患者分别为24.5 (17.2, 47.1)、25.5 (17.2, 65.5)、21.3 (19.6, 263.8)和153.0 (43.0, 525.3)μmol/L,P= 0.036]。3例患者腹部CT或MRI出现胆道系统的信号改变:包括胆囊壁增厚水肿、肝外胆管不均匀狭窄及扩张等。有2例病例有肝穿刺活检,病理可见胆管增生、胆管上皮排列不整、汇管区间质疏松水肿等胆管损伤表现。结论超过50%的PD-1相关肝损伤患者可出现胆管酶升高,提示有胆管受损;部分患者可出现胆道系统受累的影像学表现;肝脏病理对发现小胆管炎症及破坏受损有意义。

关键词: 免疫检查点抑制剂, 免疫介导胆管损伤, 碱性磷酸酶, 常见不良反应分级5.0

Abstract: Objective To explore the clinical features of immune-mediated liver injury induced by PD-1 inhibitors. Methods A retrospective study including patients with malignancies treated with PD-1 inhibitors and diagnosed with immune mediated liver injury hospitalized in Beijing Friendship Hospital between April 2016 and December 2022 was conducted. Patients were categorized into Common Terminology Criteria for Adverse Events (CTCAE) levels 0, 1, 2 and 3 based on serum alkaline phosphatase (ALP) levels classified according to CTCAE 5.0. A comparative analysis was conducted on the clinical presentations, imaging results, and pathological findings of the aforementioned groups. ANOVA test or non-parametric test was used for continuous variables, the chi-square test for categorical variables, and the Bonferroni correction for multiple comparisons. A significance level of P<0.05 is typically used to determine statistical significance. Results A total of 42 cases of immune-mediated liver injury were included in this study. Based on the ALP grading criteria outlined in CTCAE 5.0, 13 patients were classified as grade 0, 14 as grade 1, 8 as grade 2, and 7 as grade 3. Serum bilirubin levels were significantly elevated in patients classified as CTCAE grade 3 compared to those in grades 0~2 [(24.5 (17.2, 47.1), 25.5 (17.2, 65.5), 21.3 (19.6, 263.8) and 153.0 (43.0, 525.3) μmol/L, respectively P=0.036]. Three patients who underwent abdominal CT or MRI showed alterations in the biliary system, such as thickening and edema of the gallbladder wall, irregular narrowing and dilation of the extrahepatic bile duct. Additionally, two cases received liver biopsy, which revealed bile duct hyperplasia, disorganized arrangement of bile duct epithelium, and interstitial edema within the portal tract. Conclusion Over half of the patients with PD-1 related liver injury may exhibit elevated levels of bile duct enzymes, suggestive of bile duct injury. Part of the patients have imaging changes of bile duct systems. Liver pathology is significant for identifying inflammation and damage to the small bile ducts.

Key words: Immunocheckpoint inhibitors, Immune-mediated cholangiopathy, Alkaline phosphatase, Common Terminology Criteria for Adverse Events 5.0

王艳, 刘立伟, 赵梦鱼, 陈炜, 赵新颜. 胆管损伤对PD-1抑制剂相关肝损伤临床病理特征影响分析[J]. 肝脏, 2024, 29(8): 965-970.

WANG Yan, LIU Li-wei, ZHAO Meng-yu, CHEN Wei, ZHAO Xin-yan. Analysis of the influence of bile duct injury of the Clinical and pathological characteristics of immune-mediated liver injury[J]. Chinese Hepatolgy, 2024, 29(8): 965-970.

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