Specific Biomarkers of Immune-mediated Hepatitis Secondary to Immune Checkpoint Inhibitors

Recruiting

• Conditions: Immune-mediated Hepatitis
• Interventions: Biological: Blood sample collection; Procedure: Liver biopsy

• Registration Number: NCT06470997
• Lead Sponsor: University Hospital, Montpellier

Brief Summary

Identify specific blood biomarkers for hepatitis induced by immune checkpoint inhibitors in comparison to idiopathic autoimmune hepatitis.

Detailed Description

Immune checkpoint inhibitors (ICI) have become a pillar of the oncological therapeutic arsenal. Their mechanism of action is based on the restoration of the innate anti-tumor function of T lymphocytes. This mode of action is also the cause of systemic immune-mediated adverse effects. The most common disorders are endocrine, cutaneous and gastrointestinal. The frequency of hepatic toxicities is estimated between 0.7 and 25% depending on the studies, the cancer treated and the ICI combinations used. Currently the description of these hepatitis is brief in the literature and the mechanism of toxicity is not known. Work has already compared histological damage between immune checkpoint inhibitors (CHILI) and autoimmune hepatitis; The investigators find in CHILI a higher ratio of CD8 + /CD4 + lymphocytes. Apart from these clinical, biological or histological descriptions, knowledge is limited. In particular, there are no known predictive factors or prognoses.

The investigators hypothesize that there are mechanistic differences between checkpoint inhibitors induced liver injury and idiopathic autoimmune liver disease. Proteomic analysis is a powerful tool for functional analysis.

Study Timeline

• Study First Submitted: 2024-06-07
• Study First Submitted QC: 2024-06-21
• Study First Posted: 2024-06-24
• Study Start: 2024-07-17
• Status Verified: 2024-12
• Last Update Submitted: 2025-04-09
• Last Update Posted: 2025-04-10
• Primary Completion: 2025-12-01
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control group: idiopathic autoimmune hepatitis	Liver biopsy	Patient with idiopathic autoimmune hepatitis
CHILI : hepatitis induced by immune checkpoint inhibitors	Blood sample collection	Patient with immunotherapy-induced hepatitis
CHILI : hepatitis induced by immune checkpoint inhibitors	Liver biopsy	Patient with immunotherapy-induced hepatitis
Control group: idiopathic autoimmune hepatitis	Blood sample collection	Patient with idiopathic autoimmune hepatitis

Primary Outcome Measures

Name	Time	Method
Determination of the area under the ROC (Receiver Operation characteristic) curve for hepatitis.	Baseline	Sensitivity/specialty curve of blood biomarkers identification and expression level by proteomic analysis, specific to immunotherapy-induced hepatitis (CHILI group), versus idiopathic autoimmune hepatitis (control group).

Secondary Outcome Measures

Name	Time	Method
Determination of the area under the ROC (Receiver Operation characteristic) curve for treatment response	Baseline, day 14, day 28, month 3, month 6	Sensitivity/specialty curve of blood biomarkers identification and expression level by proteomic analysis, specific to response to treatments corticosteroids, UDCA (Ursodeoxycholic acid) established as part of the care).
Responses to treatments	Day 28	Response to corticosteroid and UDCA (Ursodeoxycholic acid) treatments being defined as a reduction in liver tests of 50%

Trial Locations

Locations (1)

CHU de Montpellier; 🇫🇷 Montpellier, France