Early steroid initiation may improve outcomes in immune checkpoint inhibitor-related cholangitis: a multicenter cohort study

Immune-checkpoint inhibitor (ICI)-related cholangitis is a rare but potentially fatal immune-related adverse event. In this study, we retrospectively analyzed 11 patients diagnosed with ICI-related cholangitis between 2020 and 2024 at Keio University Hospital and three affiliated hospitals. The diagnosis was based on alkaline phosphatase (ALP) elevation ≥ Common Terminology Criteria for Adverse Events Grade 2, in combination with characteristic imaging findings of bile duct dilatation or wall thickening without obstruction, after excluding other etiologies. The median ALP at onset was 437 IU/L, rising to 1304 IU/L at its peak. Total bilirubin (TB) increased from a median of 1.4 to 4.8 mg/dL during the clinical course, and worsening jaundice was observed in all fatal cases, suggesting TB as a potential prognostic indicator. All patients received steroid therapy, and seven required additional immunosuppressants, of whom six achieved at least a partial ALP response. Overall, three patients died of ICI-related cholangitis and two of the underlying malignancy. Early initiation of steroids (≤18 days from onset) was associated with reduced ICI-related mortality (p = 0.04). These findings underscore the importance of early recognition, timely initiation of steroids, and careful monitoring of bilirubin levels as a prognostic indicator in ICI-related cholangitis.