Morphology of immune-mediated hepatitis: A comparison between immune checkpoint inhibitor therapy and combined immune checkpoint inhibitor/anti-angiogenic therapy

• Published in: Annals of diagnostic pathology 2024-02, Vol.68, p.152225-152225, Article 152225
• Main Authors: Zhang, Qiongyan, Chen, Lingli, Guo, Xinxin, Shen, Licheng, Huang, Yufeng, Chen, Yi, Zhang, Ningping, Ge, Ningling, Gao, Hong, Zhang, Wen, Hou, Yingyong, Ji, Yuan
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - adverse effects; Hepatitis; Humans; Immune Checkpoint Inhibitors - adverse effects; Immunotherapy - adverse effects; Retrospective Studies
• ISSN: 1092-9134; 1532-8198
• DOI: 10.1016/j.anndiagpath.2023.152225

The combination of immune checkpoint inhibitors (ICIs) with anti-angiogenic drugs has shown promising anticancer effects. However, ICIs can trigger immune-mediated hepatitis (IMH). We aimed to clarify whether the combined use of anti-angiogenic drugs and ICIs would increase the severity of IMH. One hundred IMH patients (ICI monotherapy vs. ICI plus anti-angiogenic therapy 30 vs. 70) were retrospectively enrolled. Clinicopathological parameters were compared between the two groups. IMH mainly showed variable degrees of panlobular hepatitis (84 %), while some cases presented mixed cholangio-hepatitic (14 %) or cholangitic (2 %) pattern. The incidence of moderate-severe injury was not significantly different between the two groups (combination vs. monotherapy 38.6 % vs. 20.0 %, p = 0.109). Specifically, the rates of marked lobular injury and portal inflammation were higher in the combination group than in the monotherapy cohort (p  0.05). Compared to mild IMH cases, severe IMH cases showed higher immunostaining expression levels of PD-L1 (60.7 % vs. 19.4 %, p  0.05). Compared to ICI monotherapy, the administration of anti-angiogenic drugs in combination with ICIs was not associated with increased hepatotoxicity.