Background Pembrolizumab is a humanized recombinant monoclonal antibody to the programmed cell death receptor-1 (PD-1) which has immunomodulatory activity and is approved for treatment of many cancers. Aside from side effects associated with infusion therapy patients can develop immune related adverse events (irAEs). IrAEs occur in approximately 15-25% of patients on pembrolizumab as a result of immune enhancement leading to inflammatory toxicity. In clinical trials of pembrolizumab, less than 1% of immune mediated hepatitis (IMH) was observed, making liver toxicity an extremely rare side effect of PD1 inhibition.

Case Presentation

An 68 year-old male with urothelial cell carcinoma (UCC) who underwent radical nephroureterectomy with negative margins was found to have a suspicious mass along the surgical bed during surveillance imaging. Follow-up PET/CT confirmed a 2.4 cm mass with subsequent biopsy confirming relapse. The patient was started on Enfortumab vedotin and Pembrolizumab. Two weeks after the first cycle of therapy the patient developed colitis, tumor lysis syndrome and Steven Johnson syndrome (SJS). His liver enzymes were also elevated. Liver ultrasound was obtained shortly after due to development of ascites which showed coarsened echotexture suggestive of diffuse hepatocellular process without focal hepatic lesions. Ascitic fluid studies were negative for malignancy. CT abdomen/pelvis revealed cirrhosis not seen on imaging two weeks prior.

Discussion and Conclusion

Pembrolizumab associated hepatic injury presents after 1-3 months after initiation of treatment. Studies have shown earlier onset of liver dysfunction resulted in shortened overall survival. The pattern of injury is usually hepatocellular however there have been cases of mixed or cholestatic. Even though histology usually reflects IMH with prominent lymphocytic infiltrates of activated T cells, immunoglobulin levels are usually normal and autoantibodies are not present. Historically, fatal cases associated with immune checkpoint inhibitors (ICI) have occurred in patients with cholestatic patterns of liver injury or severe irAEs such as SJS.

Due to potentially fatal outcomes associated with liver injury, monitoring with routine liver tests should be protocol for patients receiving ICI therapy. Rapid improvement of alkaline phosphatase and bilirubin has been seen with corticosteroid treatment. In instances of inadequate response to corticosteroids alone, addition of a second immunosuppressive agent may be beneficial. However, complete recovery is rare with long-term cholestasis or hepatic failure being the eventual outcome. As ICI use becomes more prevalent, prompt recognition and proper management of irAEs will aid clinical decision making and improve outcomes.