Denosumab-Induced Immune Hepatitis.

Area of Science:

• Endocrinology
• Hepatology
• Immunology

Background:

• Denosumab (Prolia®, Xgeva®) is a monoclonal antibody targeting RANKL, used for osteoporosis and bone metastases.
• Hepatotoxicity from denosumab is exceptionally rare, with only one prior case attributed to an immune response.
• This report details a second documented case of denosumab-induced liver injury.

Observation:

• A 43-year-old female with a history of breast cancer developed elevated liver enzymes (ALT, AST) ten times the upper limit of normal.
• Liver biopsy revealed chronic inflammation, interface hepatitis, and plasma cell infiltration, indicative of drug-induced liver injury (DILI).
• The patient had received denosumab for osteoporosis prevention following endocrine therapy for breast cancer.

Findings:

• The patient presented with significant elevations in alanine aminotransferase and aspartate aminotransferase levels.
• Histopathological examination of the liver showed immune-mediated inflammation, including plasma cells and lymphocytes.
• These findings support a diagnosis of drug-induced liver injury (DILI) secondary to denosumab administration.

Implications:

• This case highlights the potential for denosumab to cause rare immune-mediated hepatotoxicity.
• Clinicians should consider DILI in patients presenting with liver enzyme abnormalities after denosumab treatment.
• Further investigation into the immunological mechanisms of denosumab-induced liver injury may be warranted.