Clinical trial NCT06864481: Prospective Cohort of Immune Checkpoint Inhibitor-induced Hepatitis
Official title: Description, Course and Treatment of Immune Checkpoint Inhibitor-induced Hepatitis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Liver Injury
Secondary to Immune Checkpoint Inhibitors
Cancer Patients
Keywords: Immune checkpoint inhibitors
Immunotherapy
Drug-induced liver injury
Hepatitis
Cholangitis
Ursodeoxycholic acid
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: Association Française pour l'Etude du Foie (AFEF)
First posted: 2025-03-07
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients will be included at the hospital

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Ratio cholestatic phenotype, cytolytic phenotype and mixed phenotype
timeFrame: Day0, Day14, Day30, Day 90, Month 6 and Month 12
Secondary outcomes:
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Montpellier University Hospital
Study officials:
References: