Specific Biomarkers of Immune-mediated Hepatitis Secondary to Immune Checkpoint Inhibitors (Pro-CHILI)

University Hospital Center (CHU)

Status

Enrolling

Conditions

Immune-mediated Hepatitis

Treatments

Procedure: Liver biopsy

Biological: Blood sample collection

Study type

Observational

Funder types

Other

Identifiers

NCT06470997

RECHMPL23_0164

Details and patient eligibility

About

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

Full 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.

Enrollment

60 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria for patients in the CHILI group:

Patient > 18 years old
Patient treated with immune checkpoint inhibitors (ICI) alone or in combination
Patient suffering from Hepatitis secondary to immune checkpoint inhibitors (ICI) grade 3 or 4 Common Terminology Criteria For Adverse Events (CTCAE)*
Treatment with corticosteroids or Ursodeoxycholic acid (UDCA) not started, or started less than 30 days ago
- Grade 3 or 4 hepatitis: increase in transaminases and/or alkaline phosphatases ≥ 5 x Upper Limit of Normal (ULN) or total bilirubin ≥ 3

Inclusion criteria for patients in the control group:

Patient > 18 years old
Patient suffering from Primary Biliary Cholangitis (PBC)* or Autoimmune Hepatitis (AIH)** or Primary Sclerosing Cholangitis (PSC) ***

Primary Biliary Cholangitis (PBC)* diagnosis :

Association of at least 2 of the following 3 criteria :

Cholestasis (PAL > 1.5N, Gamma GT > 3N) chronic (> 6 months) without ultrasound abnormality of the bile ducts.
M2 type anti-mitochondria Ab > 1/40th
Characteristic histological lesions (non-suppurative destructive cholangitis) or compatible (portal inflammation, granulomas, ductular proliferation, ductopenia, cholestasis).

** AIH diagnosis : ALT > 5 N / Ig G > 1.5 - 2 N or anti-smooth muscle ≥ 1/80 / Interface hepatitis of marked intensity The Hepactic Activity Index (HAI) score makes it possible to confirm the diagnosis when all the diagnostic criteria are not met.

*** PSC diagnosis: presence of chronic cholestasis (alkaline phosphatase > 1.5 N or GGT > 3 N) and typical abnormalities of the bile ducts on cholangio-MRI (Magnetic Resonance Imaging), and in the absence of cause of secondary sclerosing cholangitis
Treatment with corticosteroids or Ursodeoxycholic acid (UDCA) not initiated, or started less than 30 days ago

Non-inclusion criteria:

Impossibility of following the patient during the study period
Liver biopsy not possible
Other hepatitis diagnoses
Failure to obtain consent
Unemancipated minors, people unable to express their consent
Non-affiliation to a social security or equivalent scheme,
Persons placed under judicial protection,
Person participating in another research including a period of exclusion still in progress.
Pregnant or breastfeeding women
De novo or old diagnosis (at the time of a flare-up)