Indoleamine 2,3‐Dioxygenase 1 as an Adjunctive Histopathological Marker of Cholangitis Activity in Primary Biliary Cholangitis
Kaori Yoshimura, Shinji Shimoda, Ryoka Masuda, Tram Nguyen Thi, Rui Yang, Quynh Nguyen Thi, Dong Le Thanh, Yuko Tamano, Yasunori Sato, Taro Yamashita, Kenichi HaradaABSTRACT
Aim
To investigate the expression and clinicopathological significance of indoleamine 2,3‐dioxygenase 1 (IDO‐1) in primary biliary cholangitis (PBC), particularly its potential role as an adjunctive histopathological marker for diagnosis in early or atypical cases and as an indicator of disease activity.
Methods
We retrospectively analyzed 83 liver biopsy specimens from patients clinically diagnosed with or suspected of having PBC between 2016 and 2025. IDO‐1 expression in interlobular bile ducts was assessed by immunohistochemistry and correlated with clinical, biochemical, and histological features, including a new histological staging and grading system for PBC. Statistical analyses included univariate and multivariate logistic regression, and a subgroup analysis was performed for patients receiving ursodeoxycholic acid (UDCA).
Results
IDO‐1 was expressed in 64 of 83 cases (77.1%). Our multivariate analysis identified UDCA treatment (OR = 0.105, 95% CI: 0.0138–0.794, p = 0.029) and the cholangitis activity (CA) score (OR = 2.91, 95% CI: 1.18–7.18, p = 0.021) as independent predictors of IDO‐1 expression. IDO‐1 positivity was significantly reduced in UDCA‐treated patients (50.0%) compared with untreated patients (95.9%, p < 0.0001). In the UDCA subgroup, unlike other histological features, IDO‐1 expression remained significantly associated with higher CA scores.
Conclusions
IDO‐1 reflects active cholangitis rather than chronic damage such as fibrosis or bile duct loss. It is a sensitive marker of dynamic immune activity that may serve as an adjunctive histopathological marker.