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

Inclusion Criteria

• •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
• •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
• •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)