# Clinical Characteristics and Predictive Factors of Immune-Mediated Cholangitis: A Large Single-Center Retrospective Observational Study

## TL;DR

This study identifies risk factors and clinical features of immune-mediated cholangitis, a rare side effect of cancer immunotherapy, to help with early diagnosis and better patient management.

## Contribution

The study identifies baseline eosinophil count and CRP as predictors of immune-mediated cholangitis and links cholestatic injury and high NLR to poor survival in immunotherapy patients.

## Key findings

- Higher baseline eosinophil count and C-reactive protein levels are independent predictors of immune-mediated cholangitis.
- Cholestatic liver injury and elevated neutrophil-to-lymphocyte ratio are associated with poorer survival in patients with immune-mediated hepatotoxicity.
- Bile duct imaging abnormalities are common in treatment-resistant immune-mediated cholangitis cases.

## Abstract

Immune checkpoint inhibitors are widely used cancer treatments, but they can sometimes cause liver and bile duct injury. Among these reactions, immune-mediated cholangitis is rare and difficult to diagnose early because symptoms are often unclear. In this study, we examined more than 1300 treated patients to clarify who is more likely to develop this condition and how it affects outcomes. We found that people with higher levels of eosinophils or C-reactive protein before treatment were more likely to develop bile duct injury. We also learned that patients with a cholestatic pattern of liver injury or a high neutrophil-to-lymphocyte ratio tended to have poorer survival. Imaging of the bile ducts often showed abnormalities before or after symptoms appeared and may help identify patients who need closer monitoring. These findings may support earlier diagnosis and more tailored management for patients receiving immunotherapy.

Background: Immune-mediated cholangitis (IMC) is a rare complication of immune checkpoint inhibitor (ICI) therapy, and its clinical characteristics and prognostic implications remain unclear. This study aimed to clarify the characteristics, risk factors, and outcomes of IMC compared with non-cholangitis cases of immune-mediated hepatotoxicity (IMH). Methods: In this single-center retrospective study, 1332 patients who received ICIs between 2014 and 2023 were analyzed. IMH was diagnosed based on liver enzyme elevation and exclusion of other liver diseases, while IMC was identified through characteristic imaging findings. Baseline factors, clinical presentations, treatment responses, and overall survival (OS) were evaluated. Multivariate analysis identified IMC risk and IMH prognostic factors. Results: Among the cohort, 81 (6.1%) patients had IMH, including 10 (0.8%) with IMC. Baseline eosinophil count > 270/μL (odds ratio [OR] 10.33, p = 0.004) and C-reactive protein (CRP) levels > 0.8 mg/dL (OR 6.260, p = 0.027) were independent predictors of IMC. IMC was associated with delayed onset, cholestatic liver injury, abdominal pain, and neutrophil-predominant inflammation. In prognostic analysis, IMC was not associated with OS. However, cholestatic liver injury (hazard ratio [HR] 2.318, p = 0.023) and neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 (HR 3.622, p = 0.001) were independent predictors of poor OS. Bile duct imaging abnormalities before or after onset were common in patients with treatment-resistant IMC. Conclusions: Baseline eosinophil count and CRP may help predict IMC. While IMC was not a prognostic factor, cholestatic injury and high NLR were associated with worse outcomes. IMC exhibits distinct clinical features, and radiologic findings may support earlier diagnosis and management.