Bimodal onset and pan-cancer uniformity of immune-mediated liver injury: a retrospective cohort study

Bimodal onset and pan-cancer uniformity of immune-mediated liver injury: a retrospective cohort study

BackgroundImmune-mediated liver injury (IMLI) is a critical adverse event in patients treated with PD-1/PD-L1 inhibitors. The study aims to characterize the clinical heterogeneity, temporal dynamics, and immunological drivers of PD-1/PD-L1 inhibitor-associated IMLI and optimize surveillance and mana...

Full description

Saved in:
Bibliographic Details
Main Authors: Jiaojiao Song, Biying Xu, Lan Yu, Haiwei Fu, Binliang Wang, Mo Zhou, Yumin Hu, Yang Xia
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
Subjects:
immune-mediated liver injury
PD-1/PD-L1 inhibitor
clinical characteristic
immune dysregulation
management
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612287/full
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:BackgroundImmune-mediated liver injury (IMLI) is a critical adverse event in patients treated with PD-1/PD-L1 inhibitors. The study aims to characterize the clinical heterogeneity, temporal dynamics, and immunological drivers of PD-1/PD-L1 inhibitor-associated IMLI and optimize surveillance and management strategies.MethodsWe retrospectively recruited 373 IMLI patients. We evaluated clinical data, including liver injury patterns, severity, temporal trends, and immune cell subsets. Statistical analyses identified risk factors for severe IMLI and temporal dynamics.ResultsAmong 373 patients (median age: 65 years; male: 74.8%), IMLI severity was graded as G1 (53.9%), G2 (25.2%), G3 (17.9%), and G4 (2.7%), with hepatocellular (17.2%), mixed (42.6%), and cholestatic (40.2%) patterns observed. The median time to onset was 106–115 days across severity groups. In contrast, recovery time was significantly prolonged (G1/2: 14 days vs. G3/4: 23 days, P<0.05), and recovery-phase CD8+ T cells (524.9 vs. 270.68 cells/μL, P=0.026) were higher in severe cases. Bimodal onset peaks occurred at 1–2 months and 3–4 months, with 88% recovering within 100 days. No tumor-type differences existed in patterns (P=0.427) or severity (P=0.054). Elevated baseline NK cells (OR=1.004, P=0.036) predicted severe IMLI.ConclusionsIMLI demonstrates bimodal onset and pan-cancer uniformity, driven by systemic immune dysregulation. Baseline NK cells are potential predictors of severity. Risk-adapted monitoring within 4 months post-ICI and standardized protocols are recommended.
ISSN:1664-3224

Similar Items