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

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)