Checkpoint inhibitor-induced cholangiopathy

Objective Checkpoint inhibitor (CPI)-induced cholangiopathy is a rare phenotype of checkpoint inhibitor-induced liver injury (ChILI). The diagnosis is usually delayed, and its management is challenging due to lack of evidence. This review aims to summarise the current evidence on CPI-induced cholangiopathy to help physicians in the diagnosis and management in clinical practice and highlight knowledge gaps. Methods A comprehensive literature review was conducted on the incidence, clinical presentation, investigations, management and outcome of CPI-induced cholangiopathy. Results CPI-induced cholangiopathy occurs predominantly after exposure to programmed cell death protein 1 inhibitors. Most patients are asymptomatic with a mixed/cholestatic pattern of liver injury. Three-quarters of patients have bile duct abnormalities on Magnetic Resonance Cholangiopancreatography (MRCP), commonly affecting intrahepatic and extrahepatic ducts. Sclerosing cholangiopathy is seen in almost 25% with radiological abnormalities. Liver biopsy can aid in the diagnosis and exclude other pathology in those with normal imaging. CPI-induced cholangiopathy has a poor biochemical response to immunosuppression regimens recommended by oncology guidelines, while 25% improve spontaneously without any treatment. Ursodeoxycholic acid (UDCA) is commonly used, although its efficacy is unclear. Elevated liver enzymes can persist for months, with up to 20% of patients demonstrating abnormal liver enzymes for more than 6 months. Conclusion Early clinical suspicion of CPI-induced cholangiopathy is needed in all suspected ChILI with mixed/cholestatic patterns. Biliary imaging with or without biopsy is needed to establish the diagnosis. There is no evidence-based treatment, and the recovery period is usually prolonged. Response to immunosuppression is limited and initiating UDCA can be considered in all patients.