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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-07-17

Study Completion Date

2027-01-31

Brief Summary

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

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Detailed Description

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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.

Conditions

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Immune-mediated Hepatitis

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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CHILI : hepatitis induced by immune checkpoint inhibitors

Patient with immunotherapy-induced hepatitis

Blood sample collection

Intervention Type BIOLOGICAL

6 collections of 5mL blood samples as part of usual care (pre-inclusion visit at Day-7, inclusion visit at Day 0, visit1 at Day 14, visit2 at Day 28, visit3 at Day 90, visit4 at 6 months) and 5 blood sample collections of 5 mL for proteomic analysis in the context of research (inclusion visit at Day 0, visit1 at Day 14, visit2 at Day 28, visit3 at Day 90, visit4 at 6 months)

Liver biopsy

Intervention Type PROCEDURE

1 liver biopsy performed as part of routine care and 1 additional sample for research: transparietal needle biopsy under ultrasound identification under local anesthesia by a radiologist, 1 to 2 cm per core taken, 2 cores are taken.

Control group: idiopathic autoimmune hepatitis

Patient with idiopathic autoimmune hepatitis

Blood sample collection

Intervention Type BIOLOGICAL

6 collections of 5mL blood samples as part of usual care (pre-inclusion visit at Day-7, inclusion visit at Day 0, visit1 at Day 14, visit2 at Day 28, visit3 at Day 90, visit4 at 6 months) and 5 blood sample collections of 5 mL for proteomic analysis in the context of research (inclusion visit at Day 0, visit1 at Day 14, visit2 at Day 28, visit3 at Day 90, visit4 at 6 months)

Liver biopsy

Intervention Type PROCEDURE

1 liver biopsy performed as part of routine care and 1 additional sample for research: transparietal needle biopsy under ultrasound identification under local anesthesia by a radiologist, 1 to 2 cm per core taken, 2 cores are taken.

Interventions

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Blood sample collection

6 collections of 5mL blood samples as part of usual care (pre-inclusion visit at Day-7, inclusion visit at Day 0, visit1 at Day 14, visit2 at Day 28, visit3 at Day 90, visit4 at 6 months) and 5 blood sample collections of 5 mL for proteomic analysis in the context of research (inclusion visit at Day 0, visit1 at Day 14, visit2 at Day 28, visit3 at Day 90, visit4 at 6 months)

Intervention Type BIOLOGICAL

Liver biopsy

1 liver biopsy performed as part of routine care and 1 additional sample for research: transparietal needle biopsy under ultrasound identification under local anesthesia by a radiologist, 1 to 2 cm per core taken, 2 cores are taken.

Intervention Type PROCEDURE

Eligibility Criteria

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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)

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No