S3410 Distinguishing Immune Checkpoint Inhibitor-Induced Cholangitis From Hepatitis

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized oncology treatment options, but also introduced immune-related adverse events. ICI-induced cholangitis (ICIIC) is a rare complication. Here, we present a case of ICIIC that was initially managed as ICI-induced hepatitis (ICIIH). Case Description/Methods: A 70-year-old man with metastatic renal cell carcinoma initiated on ipilimumab and nivolumab a month ago, type 2 diabetes, and hyperlipidemia, presented to the hospital after outpatient oncology clinic labs incidentally revealed elevated liver enzymes. He denied abdominal pain, bloating, jaundice, pale stools, nausea, vomiting, fatigue, fevers or chills. He denied any alcohol use or herbal supplementation and had been ingesting a maximum of 650 mg of acetaminophen daily. Initial labs were notable for: aspartate transaminase (AST) 329, alanine aminotransferase (ALT) 390, alkaline phosphatase (ALP) 1167, and total bilirubin 1.5, all of which were previously within normal ranges. His gamma-glutamyl transferase was 757, and international normalized ratio 1.5. Hepatitis serologies ruled out acute and chronic infections. Magnetic resonance cholangiopancreatography upon presentation showed cholelithiasis, no biliary dilatation, and a hepatic lesion suspicious for metastasis. He was started on intravenous methylprednisolone 1 mg/kg for presumed ICIIH, which was subsequently increased to 2 mg/kg when liver enzymes did not improve. Gastroenterology/Hepatology was consulted, and recommended initiating ursodeoxycholic acid (UDCA) 15 mg/kg/day and decreasing steroids to 1 mg/kg. His liver enzymes improved to AST 28, ALT 73, ALP 434, and total bilirubin 0.5. He was discharged with a steroid taper. Discussion: Given the cholestatic pattern of injury and clear temporal correlation with immunotherapy initiation, a diagnosis of small duct ICIIC was made. ICIIC is mostly associated with anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) agents, both of which this patient received. Through altering anti-tumor immunity, a loss of self-tolerance can lead to immune-mediated attack on small and/or large biliary ducts, which can cause liver failure and death if untreated. The incidence of ICIIC is not well characterized. In contrast to ICIIH, which is treated with immunosuppression, management of ICIIC also includes UDCA, due to its choleretic and immunomodulatory properties. Timely diagnosis and management of ICIIC are critical for patients undergoing ICI therapy.