An Unusual Case of Cholestatic Drug-Induced Liver Injury Following a Single Dose of Pembrolizumab

Abstract

Introduction: Pembrolizumab is a humanized recombinant monoclonal antibody to the programmed cell death receptor-1 used in the treatment of advanced melanoma and non-small cell lung cancer. It is thought to cause liver injury through an immune mediated mechanism, usually in a hepatocellular pattern. Case Presentation: An 82-year old male with a history of Metastatic Melanoma presented with painless jaundice. He was diagnosed with melanoma in 2015 and treated with surgical resection. He presented 1 year later with confusion and was found to have metastatic CNS lesions. He was again treated surgically and on discharge, he was noted to have a normal hepatic function panel. 1 week later, he was given his first dose of Pembrolizumab. 6 days later, he developed painless jaundice. On exam, the patient was jaundiced and had no stigmata of chronic liver disease. Labs revealed a total bilirubin of 12.0 mg/dL with direct component of 10.4 mg/dL. Alkaline phosphatase was 1873 IU/L, AST 621 IU/L, ALT 616 IU/L, Albumin 2.3 g/dL and INR 2.99. The R Score was 0.76 upon admission. Serologic work up was negative for acute viral hepatitis and autoimmune hepatitis. Abdominal Ultrasound showed no hepatic abnormalities and the common bile duct measured 3 mm. Doppler exam showed no evidence of occlusion. MRCP showed no evidence of biliary disease. Transjugular liver biopsy was performed. Pathology revealed acute hepatitis with marked cholestasis without evidence of metastatic melanoma. He was empirically started on corticosteroid therapy without improvement. Unfortunately, he developed worsening multi-organ failure and ultimately the decision was made to pursue palliative measures. Discussion: Pembrolizumab is known to cause liver injury, usually in a hepatocellular pattern. Approximately 10 percent of patients will develop mild to moderate elevations in serum AST/ALT levels, which are usually self-limited. Elevations greater than 5 times the upper limit of normal can be seen in 0.5 to 1.5% of patients. The onset of injury is usually after 2-6 cycles, as opposed to one cycle in our patient. The mechanism of injury is immunologically mediated and early treatment with immunosuppressive therapy generally results in resolution. Pathology shows an acute hepatitis-like pattern with necrosis and a prominent lymphocytic infiltrates, which was not seen in our patient. Autoantibodies are usually not present and immunoglobulin levels may not be elevated.