Pembrolizumab-Induced Secondary Cholangitis: A Case Report

Immune checkpoint inhibitors (ICIs) are increasingly being used as part of cancer treatment. Whilst effective oncological therapies, these drugs are associated with a significant risk of immune-related adverse events (IrAEs). They can affect a variety of organ systems, including the lungs, heart, kidneys, and gastrointestinal tract, with liver damage being a relatively well-recognised complication. There have been multiple previous reports describing immune-related hepatitis; however, more recent studies are starting to describe inflammation within the extrahepatic and intrahepatic bile ducts, specifically discussing immune-related cholangitis. This can be in addition to or distinct from hepatitis. Immune-related cholangitis remains rare and less extensively studied than other complications; however, it represents a significant adverse event that may evolve into potentially severe complications such as liver failure and can be fatal. We present a case of a 50-year-old man with non-small cell lung carcinoma (NSCLC) with brain metastases, who developed immune-related cholangitis following 11 cycles of the immune checkpoint inhibitor pembrolizumab. The patient presented with severe abdominal pain and transaminitis. A comprehensive workup excluded bacterial, viral, autoimmune and other alternative aetiologies leading up to the diagnosis of ICI-induced cholangitis, based on magnetic resonance cholangiopancreatography (MRCP). The patient responded well to the combination of ursodeoxycholic acid (UDCA), corticosteroid therapy and mycophenolate mofetil (MMF), showing gradual improvement in liver enzyme levels and significant improvement in abdominal pain. At the time of writing this case report, subsequent slow steroid weaning has been successful, without clinical or biochemical flare. As the use of ICIs increases, this case highlights the importance of awareness of immune-related cholangitis as a rare but significant adverse event to enable a timely diagnosis and treatment. Immune-related cholangitis such as this is crucial to identify as distinct from infective cholangitis, as treatment is primarily immunosuppression. It adds to the growing body of evidence of immune-related cholangitis as a specific adverse reaction, encouraging and enabling more research into this to guide future clinical decision-making and the formation of treatment guidance and diagnostic criteria.