Immune Checkpoint Inhibitor-Induced Hepatic Injury: A Clinicopathologic Review

Although immune checkpoint inhibitors (ICIs) have been a revolutionary milestone in immuno-oncology, immune-related adverse events (irAEs) may occur due to enhanced T cell activation and immune dysregulation. The irAEs can occur as early as within days to reportedly as late as up to 26 weeks. They may affect any organ system in the body, most commonly the luminal gastrointestinal tract, liver, skin, endocrine system, and lungs. The mechanisms of irAEs are complex and have not been fully understood. A breach of self-tolerance, which leads to autoantigen reactivity due to the enhanced activation and infiltration of T cells or the production of autoantibodies, and a non-specific autoinflammatory mechanism have been proposed. Limited data is available on the clinical and pathologic features of ICI-induced liver injury. This review presents an overview of the clinical and common histopathologic features and patterns of ICI-induced liver injury, the differential diagnoses, and the clinical management. Available data suggest that the histopathologic findings of ICI-induced hepatic injury are often non-specific and overlap with other challenging differential diagnoses. Therefore, a good knowledge of the histopathologic spectrum of ICI-induced hepatic injury and their differential diagnoses combined with the serological test results, clinical correlation, and communication with the clinical team is necessary to make an accurate and timely diagnosis.