Immune-Mediated Liver Injury From Checkpoint Inhibitor: An Evolving Frontier With Emerging Challenges

Area of Science:

• Oncology
• Immunology
• Hepatology

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment.
• Immune-related adverse events (irAEs), including Immune-mediated Liver Injury from Checkpoint Inhibitors (ILICI), are significant risks.
• ILICI can necessitate treatment cessation and immunosuppression.

Purpose of the Study:

• To review current knowledge on risk factors, presentation, and treatment of ILICI.
• To discuss ILICI refractory to steroids and the potential for immunotherapy rechallenge.
• To identify knowledge gaps and areas for future research in ILICI.

Main Methods:

• Literature review of Immune-mediated Liver Injury from Checkpoint Inhibitors (ILICI).
• Analysis of clinical presentation, risk factors, and treatment strategies.
• Discussion of emerging concepts like immunotherapy rechallenge.

Main Results:

• ILICI presentation is heterogeneous, varying in onset, injury pattern (hepatitis vs. cholangitis), and severity.
• Cytotoxic T Lymphocytes (CTLs) are key, but immunotherapy affects the entire immune microenvironment.
• Steroid-refractory ILICI and rechallenge strategies present clinical challenges.

Conclusions:

• Understanding ILICI is crucial for managing cancer immunotherapy side effects.
• Further research is needed to address heterogeneity, refractory cases, and safe rechallenge protocols.
• Optimizing management of ILICI can improve patient outcomes on immunotherapy.