Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events.
Details
Serval ID
serval:BIB_F836C2B098EA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events.
Journal
Journal for immunotherapy of cancer
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Publication state
Published
Issued date
10/2022
Peer-reviewed
Oui
Volume
10
Number
10
Pages
e005635
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Immune checkpoint inhibitors (ICIs) have become a mainstay of cancer treatment. Their immune-boosting quality has one major drawback, their proclivity to induce a broad array of immune-related adverse events (irAEs) affecting, among others, the liver and sharing some similarities with classic autoimmune liver diseases (AILD).We aimed to compare clinical, laboratory and histological features of patients with liver-related irAEs and AILD.
We systematically compared liver irAEs with AILD, namely autoimmune hepatitis (AIH) and primary biliary cholangitis, regarding their clinical, laboratory, and histological features.
Twenty-seven patients with liver irAEs (ICI group) and 14 patients with AILD were identified. We observed three distinct ICI-induced histological liver injury patterns: hepatitic (52%), cholangitic (19%), and mixed (29%). When comparing the ICI and AILD groups, centrilobular injury as well as granuloma formation were more prevalent in the former (p=0.067 and 0.002, respectively). CD4+/CD8+ T cell ratios were heterogeneous between the two groups, without statistically significant difference but with a trend toward increased CD8+ T cells among hepatitic irAEs as compared with AIH. Pattern of liver function test alteration was predictive for the type of irAEs but did not correlate with histological severity.
Liver irAEs have broad clinical, laboratory and histological presentations. Histological features of irAEs and AILD are distinct, likely underpinning their different immunological mechanisms.
We systematically compared liver irAEs with AILD, namely autoimmune hepatitis (AIH) and primary biliary cholangitis, regarding their clinical, laboratory, and histological features.
Twenty-seven patients with liver irAEs (ICI group) and 14 patients with AILD were identified. We observed three distinct ICI-induced histological liver injury patterns: hepatitic (52%), cholangitic (19%), and mixed (29%). When comparing the ICI and AILD groups, centrilobular injury as well as granuloma formation were more prevalent in the former (p=0.067 and 0.002, respectively). CD4+/CD8+ T cell ratios were heterogeneous between the two groups, without statistically significant difference but with a trend toward increased CD8+ T cells among hepatitic irAEs as compared with AIH. Pattern of liver function test alteration was predictive for the type of irAEs but did not correlate with histological severity.
Liver irAEs have broad clinical, laboratory and histological presentations. Histological features of irAEs and AILD are distinct, likely underpinning their different immunological mechanisms.
Keywords
Humans, Antineoplastic Agents, Immunological/adverse effects, Immune Checkpoint Inhibitors/adverse effects, Immunotherapy/adverse effects, Neoplasms, Immune System Diseases/chemically induced, Liver Diseases/etiology, Liver Diseases/drug therapy, Hepatitis, Autoimmune/etiology, Hepatitis, Autoimmune/drug therapy, CTLA-4 antigen, autoimmunity, cytotoxicity, immunologic, immunotherapy, programmed cell death 1 receptor
Pubmed
Web of science
Open Access
Yes
Create date
26/10/2022 12:25
Last modification date
14/12/2022 6:54