Hepatology (Liver and Bile Duct)

Immune-mediated hepatobiliary toxicity is one of the immune-related adverse events that could occur after initiating treatment with an immune checkpoint inhibitor. Importantly, it is a diagnosis of exclusion. Three important phenotypes of this toxicity have been recognized: hepatitic, cholangiopathic, and an “overlap” of both features. Although no pathognomonic features have yet been defined in this entity, published analyses on the histologic features can aid in building confidence toward the diagnosis - particularly when committing patients to immunosuppressive therapy - while excluding alternative diagnoses such as autoimmune hepatitis, which must be distinguished from an immunotherapy-mediated cause. Immunotherapy-mediated hepatobiliary toxicity is traditionally treated with corticosteroids in cases of moderate-to-severe disease. The severity of injury affects the management. Mild injury can be monitored closely while continuing immunotherapy, whereas more severe cases require the cessation of immunotherapy in favor of immunosuppressive treatment. Emerging clinical experience and new literature are changing the landscape of approaches to diagnosis and optimal treatments. Complex cases often relate to unsatisfactory response to standard treatment with steroids, particularly if remission is not achieved after adjunctive therapies are added, or if the patient has a pre-existing underlying chronic liver disease condition. While many patients successfully respond to steroid-based immunosuppressive therapy, a subset of steroid-refractory or steroid-dependent cases represents an important area of unmet need. Several aspects of immune-mediated hepatobiliary toxicity require ongoing research, including its pathophysiologic mechanisms, risk factors for onset, and optimal treatments.