Delayed-Onset Immune-Mediated Hepatitis Following Pembrolizumab Discontinuation: A Case Report

Immune checkpoint inhibitors (ICIs) such as pembrolizumab (Keytruda) have transformed the treatment landscape for various malignancies, yet they are associated with immune-related adverse events (irAEs), including hepatotoxicity. While most cases of ICI-induced hepatitis occur within weeks of initiating therapy, delayed-onset presentations are increasingly recognized. We report a case of severe transaminase elevation developing three months after cessation of pembrolizumab in a patient with a history of gallbladder carcinoma. Her chemotherapy was placed on hold after a recent stroke led to a worsening functional status, with the initial intent to resume pembrolizumab once her functional status normalized. Workup excluded infectious, metabolic, and autoimmune causes. Liver biopsy revealed immune-mediated hepatitis with histologic evidence of only mild cholestasis. The patient responded to corticosteroid therapy, supporting the diagnosis of ICI-induced hepatotoxicity. This case underscores the importance of maintaining a high index of suspicion for immune-mediated liver injury well beyond the period of active immunotherapy and highlights the diagnostic value of liver biopsy in complex presentations.