Autoimmune hepatitis following long-term denosumab therapy in a patient with Hashimoto thyroiditis.

Denosumab, a receptor activator of nuclear factor-κB ligand (RANKL) inhibitor, is widely used to treat osteoporosis. Its role as a trigger for autoimmune hepatitis (AIH) remains uncertain. We report a 68-year-old woman with osteoporosis and Hashimoto thyroiditis who developed jaundice and severe hepatocellular liver injury after 3 years of denosumab therapy. Alternative viral, obstructive, and metabolic causes were excluded. Liver biopsy demonstrated interface hepatitis with a lymphoplasmacytic portal infiltrate consistent with AIH, and autoimmune serologies were positive. Hemophagocytic lymphohistiocytosis was excluded, and an International AIH Score of 17 supported a diagnosis of definite AIH. Treatment with corticosteroid-based immunosuppression resulted in complete biochemical remission, and denosumab was discontinued with transition to zoledronic acid to prevent rebound bone loss. Whether this case represents drug-induced autoimmune-like hepatitis or de novo idiopathic AIH occurring in a susceptible individual cannot be determined definitively. Clinicians should maintain a low threshold for evaluating liver injury in patients receiving denosumab who develop jaundice or marked transaminase elevation.