Prospective Cohort of Immune Checkpoint Inhibitor-induced Hepatitis (CO-CHILI)

Description, Course and Treatment of Immune Checkpoint Inhibitor-induced Hepatitis

Background and Study Rationale Immune checkpoint inhibitors (ICI) are a breakthrough cancer treatment that boosts the immune system to fight tumors. While effective, they can cause immune-related side effects, including liver inflammation (ICI-induced hepatitis or CHILI), which affects up to 25% of patients. Severe cases requiring treatment discontinuation are rare but challenging to manage.

Study Objective This multicenter prospective study aims to better understand CHILI, its clinical patterns, treatment response, and risk of recurrence. It will focus on different types of liver injury (cholestatic, hepatocellular, or mixed) to guide better treatment decisions.

Innovation and Approach Currently, there is no clear consensus on how to manage CHILI or when to safely restart immunotherapy. This study will collect real-world data from adult patients treated with ICIs, following international guidelines or a pragmatic approach when no consensus exists. Findings will help improve care strategies for patients experiencing ICI-related liver toxicity.

Study Overview

• Status: Recruiting
• Conditions: Cancer Patients; Liver Injury; Secondary to Immune Checkpoint Inhibitors
• Intervention / Treatment: Other: Blood samples

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Lucy MEUNIER, M.D; Phone Number: Phone: +33467330224; Email: lucy-meunier@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France, 34295
    • Recruiting
    • Montpellier University Hospital
    • Contact: Lucy MEUNIER, MD; Phone Number: +33 +33467330224; Email: lucy-meunier@chu-montpellier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients will be included at the hospital

Description

Inclusion criteria:

• Age ≥ 18 years

  • Patient willing to participate in the study
  • Patient with cancer receiving neoadjuvant, adjuvant, or maintenance treatment · Patient treated with ICI, either as monotherapy or in combination with another antitumor treatment (targeted therapy, chemotherapy, or radiotherapy), either de novo or after a first-line treatment including ICIs
  • Patient who has received at least one injection of an ICI ·

  • Onset of hepatitis following treatment initiation, defined by the following criteria:

    • ALT (alanine aminotransferase) ≥ 5 times the upper normal limit
    • ALP (alkaline phosphatase) ≥ 2 times the upper normal limit
    • ALT (alanine aminotransferase) ≥ 3 times the upper normal limit and bilirubin ≥ 2 times the upper normal limit ·
  • Patient with grade 3 or 4 hepatitis, according to the current CTCAE classification
  • Exclusion criteria:
• Patient with another cause of acute hepatitis, including viral, autoimmune, ischemic, acute alcoholic hepatitis, or Wilson's disease.
• Patient unable to express their non-opposition to participate in the study.
• Person deprived of liberty, under guardianship or curatorship, or in an emergency situation.
• Person not affiliated with a social security system or without entitlement to healthcare coverage.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Immune Checkpoint Inhibitor-Induced Hepatitis; Observational cohort	Other: Blood samples; one Blood sample (20 ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ratio cholestatic phenotype, cytolytic phenotype and mixed phenotype	Day0, Day14, Day30, Day 90, Month 6 and Month 12

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Association Française pour l'Etude du Foie (AFEF)

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2025
• Primary Completion (Estimated): April 22, 2028
• Study Completion (Estimated): April 22, 2028

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: March 3, 2025
• First Posted (Actual): March 7, 2025

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; Hepatitis; Ursodeoxycholic acid; Immune checkpoint inhibitors; Cholangitis; Drug-induced liver injury
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Hepatitis
• Other Study ID Numbers: RECHMPL24_0283

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No