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Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint
Alexander Coukos1, Julien Vionnet1,2, Michel Obeid3
1Gastroenterology and Hepatology, CHUV, Lausanne, Switzerland.
Background:
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.
Methods:
We systematically compared liver irAEs with AILD, namely autoimmune hepatitis (AIH) and primary biliary cholangitis, regarding their clinical, laboratory, and histological features.
Results:
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.
Conclusions:
Liver irAEs have broad clinical, laboratory and histological presentations. Histological features of irAEs and AILD are distinct, likely underpinning their different immunological mechanisms.
Insights
Immune checkpoint inhibitors (ICIs) can cause liver injury, presenting distinct histological features compared to autoimmune liver diseases (AILD). Understanding these differences is key for accurate diagnosis and management of ICI-induced liver injury.
Area of Science:
- Hepatology
- Immunology
- Oncology
Background:
- Immune checkpoint inhibitors (ICIs) are crucial cancer therapies but can induce immune-related adverse events (irAEs), including liver injury.
- Liver irAEs share clinical similarities with autoimmune liver diseases (AILD), necessitating differentiation.
Purpose of the Study:
- To compare the clinical, laboratory, and histological characteristics of liver irAEs and AILD.
- To identify distinct features that differentiate ICI-induced liver injury from classic autoimmune liver conditions.
Main Methods:
- Systematic comparison of liver irAEs with autoimmune hepatitis (AIH) and primary biliary cholangitis.
- Analysis of clinical, laboratory, and histological data from patients with liver irAEs and AILD.
Main Results:
- Three histological patterns of ICI-induced liver injury were observed: hepatitic (52%), cholangitic (19%), and mixed (29%).
- Centrilobular injury and granuloma formation were more frequent in ICI-induced liver injury.
- Liver function test patterns predicted irAE type but not histological severity.
Conclusions:
- Liver irAEs exhibit diverse clinical, laboratory, and histological presentations.
- Histological findings in liver irAEs are distinct from AILD, suggesting different underlying immunological mechanisms.
