Immune checkpoint inhibitor-associated hepatitis and colitis: current understanding and clinical approaches

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by harnessing the immune system to target tumors. The introduction of ipilimumab, an anti-CTLA-4 monoclonal antibody, marked a major milestone in immuno-oncology when it was approved by the U.S. Food and Drug Administration (FDA) in 2011 for advanced melanoma. By blocking CTLA-4, ipilimumab enhances T-cell activation and promotes antitumor immunity. Subsequent development and approval of anti-PD-1 and anti-PD-L1 antibodies, such as nivolumab and pembrolizumab, since 2014 have broadened the scope of ICI therapy to various malignancies, often demonstrating improved tolerability relative to CTLA-4 inhibition. While these agents have significantly improved clinical outcomes, they also disrupt immune homeostasis, leading to immune-related adverse events (irAEs), in which healthy tissues are attacked by the immune system. Among these, gastrointestinal irAEs - including hepatitis and colitis - are frequently observed and may require intensive management. These toxicities are immunologically mediated and differ substantially from adverse effects associated with conventional cytotoxic chemotherapy. As ICIs gain broader indications clinicians must be prepared to identify and manage irAEs promptly. This review provides an in-depth discussion of ICI-associated gastrointestinal toxicities, emphasizing their epidemiology, immunopathogenesis, diagnostic strategies, and therapeutic management, in line with the latest clinical guidelines from major oncological societies such as ASCO and ESMO.