Pathologic Changes in Ipilimumab-Related Hepatitis in Patients with Metastatic Melanoma

Ipilimumab is a fully human monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, an immune checkpoint molecule that down-regulates pathways of T-cell activation. Ipilimumab has demonstrated a statistically significant improvement in overall survival in two randomized controlled phase III trials of patients with metastatic melanoma. A main complication of ipilimumab therapy is the development of inflammatory events which can occur in various organs, including the liver (i.e., hepatitis). Hepatic injury is a concern because it can develop with little warning and may potentially be severe. We analyzed liver biopsy findings in 4 cases of ipilimumab treatment-related hepatitis and compared them to a fifth, previously reported case. All 5 patients had a histologic pattern of injury that was similar to what is observed with acute viral and autoimmune hepatitis; however, the findings are not specific and require clinicopathologic correlation. Pathologic evidence of hepatitis resolved in all 5 patients with appropriate immunosuppressive therapy. Although a relatively uncommon adverse event with ipilimumab, patients should be monitored at regular intervals for biochemical/pathological evidence of hepatitis.