Pathological features of immune-mediated hepatitis due to immune checkpoint inhibitors and anti-angiogenesis targeted therapy
10.3760/cma.j.cn112151-20190720-00403
- VernacularTitle:免疫检查点抑制剂治疗后肝功能异常的组织病理学分析
- Author:
Qiongyan ZHANG
1
;
Lingli CHEN
;
Feng GAO
;
Akesu SUJIE
;
Yingyong HOU
;
Xiaowu HUANG
;
Cheng HUANG
;
Huichuan SUN
;
Jian ZHOU
;
Yuan JI
Author Information
1. 复旦大学附属中山医院病理科，上海 200032
- Keywords:
Liver neoplasms;
Hepatitis;
Immune checkpoint inhibitors
- From:
Chinese Journal of Pathology
2020;49(4):329-335
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To compare the histologic features of immune-mediated hepatitis (IMH) due to immune checkpoint inhibitors (ICIs) monotherapy and combined ICIs anti-angiogenesis tyrosine kinases (TKIs) targeted therapy.Methods:Twenty-one IMH patients who had liver biopsy during ICIs treatment in Zhongshan Hospital of Fudan University from 2015 to 2019 were included. Among them, ten were treated with ICIs monotherapy, and 11 were treated with combined ICIs and anti-angiogenesis targeted therapy. The histologic features of IMH were assessed by HE staining and PD-L1/2 was evaluated by immunohistochemical staining.Results:Patients treated with monotherapy ICIs presented with different levels of lobular hepatitis and portal inflammation. Besides, there were also cholangitis, endothelialitis, Kupffer cells activation and peliosisi hepatitis. Eight cases (8/10) showed mild and two cases (2/10) showed moderate hepatic injury. As for patients receiving combined ICIs and TKIs therapy, the extent of IMH was more severe, with four cases (4/11) showing moderate-severe liver injury, with confluent or bridging necrosis, portal inflammation, cholangitis, interface hepatitis. Among these, one patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction. In those cases with severe liver injury, many CD8 positive lymphocytes aggregated in the portal area and hepatic sinusoid, and PD-L1 was expressed in many endothelial cells. There were both 2 cases of death in ICIs monotherapy and combination therapy group. Among the latter group, 1 patient developed acute severe hepatitis with massive hepatocyte necrosis and died of multisystem dysfunction.Conclusion:Compared with ICIs monotherapy, combined ICIs and anti-angiogenesis targeted TKIs therapy may cause overlapping hepatic injury, leading to severe IMH.
