AzTrials
AzTrials

Immune-mediated HepatitisPro-CHILINCT06470997

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

An observational study of Immune-mediated Hepatitis, run by University Hospital, Montpellier at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Identify specific blood biomarkers for hepatitis induced by immune checkpoint inhibitors in comparison to idiopathic autoimmune hepatitis. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Immune-mediated Hepatitis
What is being tested?
Blood sample collection and Liver biopsy
Type of treatment
Surgery or procedure
How many people
60 participants
Where
1 siteFrance
Study dates
17 Jul 2024to 31 Jan 2027
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: CHILI group: patients with hepatitis induced by immune checkpoint inhibitors Control group: patients with idiopathic autoimmune hepatitis

Who may be able to join

  • 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
Show all 26Show fewer
  • 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)

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Lucy MEUNIER, MD contact

0467330224

lucy-meunier@chu-montpellier.fr

Lina HOUNTONDJI, MD contact

l-hountondji@chu-montpellier.fr

France1 site, 1 recruiting

  • CHU de Montpellier

    Montpellier, France, 34295

    Lucy MEUNIER, MD

    Recruiting

Other trials in France

About this study

Official title: Specific Biomarkers of Immune-mediated Hepatitis Secondary to Immune Checkpoint

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

Read the detailed 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.

Being tested
Blood sample collection, Liver biopsy
Keywords
proteomic analysis, blood biomarker, immune-mediated hepatitis secondary to immune checkpoint inhibitors, idiopathic autoimmune hepatitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood sample collectionBiological

    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 biopsyProcedure or surgery

    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.

Study groups in NCT06470997
Study groupRoleWhat they receive
CHILI : hepatitis induced by immune checkpoint inhibitorsPatient with immunotherapy-induced hepatitis
Receives: Biological: Blood sample collection; Procedure: Liver biopsy
Control group: idiopathic autoimmune hepatitisPatient with idiopathic autoimmune hepatitis
Receives: Biological: Blood sample collection; Procedure: Liver biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determination of the area under the ROC (Receiver Operation characteristic) curve for hepatitis.

    Sensitivity/specialty curve of blood biomarkers identification and expression level by proteomic analysis, specific to immunotherapy-induced hepatitis (CHILI group), versus idiopathic autoimmune hepatitis (control group).

    Measured: Baseline

Secondary outcomes (2)

  1. Determination of the area under the ROC (Receiver Operation characteristic) curve for treatment response

    Sensitivity/specialty curve of blood biomarkers identification and expression level by proteomic analysis, specific to response to treatments corticosteroids, UDCA (Ursodeoxycholic acid) established as part of the care).

    Measured: Baseline, day 14, day 28, month 3, month 6

  2. Responses to treatments

    Response to corticosteroid and UDCA (Ursodeoxycholic acid) treatments being defined as a reduction in liver tests of 50%

    Measured: Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jun 2024
  2. Study start17 Jul 2024
  3. Primary completion18 Jan 2027 (estimated)
  4. Study completion31 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Other
Time perspective
Prospective
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06470997
Sponsor's protocol ID
RECHMPL23_0164
Acronym
Pro-CHILI
Status last verified
Nov 2025
First submitted
7 Jun 2024
Last updated
21 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • De Martin E, Michot JM, Rosmorduc O, Guettier C, Samuel D. Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors. JHEP Rep. 2020 Aug 11;2(6):100170. doi: 10.1016/j.jhepr.2020.100170. eCollection 2020 Dec.

    PubMed 33205034

  • Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A, Carbonnel F, Cauquil C, Chanson P, Collins M, Durrbach A, Ederhy S, Feuillet S, Francois H, Lazarovici J, Le Pavec J, De Martin E, Mateus C, Michot JM, Samuel D, Soria JC, Robert C, Eggermont A, Marabelle A. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol. 2016 Apr;27(4):559-74. doi: 10.1093/annonc/mdv623. Epub 2015 Dec 28.

    PubMed 26715621

  • Peeraphatdit TB, Wang J, Odenwald MA, Hu S, Hart J, Charlton MR. Hepatotoxicity From Immune Checkpoint Inhibitors: A Systematic Review and Management Recommendation. Hepatology. 2020 Jul;72(1):315-329. doi: 10.1002/hep.31227.

    PubMed 32167613

  • Haanen J, Obeid M, Spain L, Carbonnel F, Wang Y, Robert C, Lyon AR, Wick W, Kostine M, Peters S, Jordan K, Larkin J; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Dec;33(12):1217-1238. doi: 10.1016/j.annonc.2022.10.001. Epub 2022 Oct 18. No abstract available.

    PubMed 36270461

  • Zen Y, Yeh MM. Hepatotoxicity of immune checkpoint inhibitors: a histology study of seven cases in comparison with autoimmune hepatitis and idiosyncratic drug-induced liver injury. Mod Pathol. 2018 Jun;31(6):965-973. doi: 10.1038/s41379-018-0013-y. Epub 2018 Feb 5.

    PubMed 29403081

  • Hountondji L, Ferreira De Matos C, Lebosse F, Quantin X, Lesage C, Palassin P, Rivet V, Faure S, Pageaux GP, Assenat E, Alric L, Zahhaf A, Larrey D, Witkowski Durand Viel P, Riviere B, Janick S, Dalle S, Maria ATJ, Comont T, Meunier L. Clinical pattern of checkpoint inhibitor-induced liver injury in a multicentre cohort. JHEP Rep. 2023 Mar 7;5(6):100719. doi: 10.1016/j.jhepr.2023.100719. eCollection 2023 Jun.

    PubMed 37138674

  • Coukos A, Vionnet J, Obeid M, Bouchaab H, Peters S, Latifyan S, Wicky A, Michielin O, Chtioui H, Moradpour D, Fasquelle F, Sempoux C, Fraga M. Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2022 Oct;10(10):e005635. doi: 10.1136/jitc-2022-005635.

    PubMed 36283734

  • Gudd CLC, Au L, Triantafyllou E, Shum B, Liu T, Nathwani R, Kumar N, Mukherjee S, Dhar A, Woollard KJ, Yone Y, Pinato DJ, Thursz MR, Goldin RD, Gore ME, Larkin J, Khamri W, Antoniades CG, Turajlic S, Possamai LA. Activation and transcriptional profile of monocytes and CD8+ T cells are altered in checkpoint inhibitor-related hepatitis. J Hepatol. 2021 Jul;75(1):177-189. doi: 10.1016/j.jhep.2021.02.008. Epub 2021 Feb 22.

    PubMed 33631227

  • Yoshimura K, Tamano Y, Nguyen Canh H, Zihan L, Le Thanh D, Sato Y, Terashima T, Shimoda S, Harada K. A novel pathologic marker, indoleamine 2,3-dioxygenase 1, for the cholangiopathy of immune checkpoint inhibitors-induced immune mediated hepatotoxicity as adverse events and the prediction of additional ursodeoxycholic acid treatment. Med Mol Morphol. 2023 Jun;56(2):106-115. doi: 10.1007/s00795-022-00344-7. Epub 2023 Jan 4.

    PubMed 36599971

Questions about this trial

What is this clinical trial studying?

An observational study of Immune-mediated Hepatitis, run by University Hospital, Montpellier at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 21 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Lucy MEUNIER, MD (0467330224, lucy-meunier@chu-montpellier.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determination of the area under the ROC (Receiver Operation characteristic) curve for hepatitis. (time frame: Baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06470997, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in