Immune-Mediated HepatitisChILINCT04476563
Checkpoint Inhibitor-induced Liver Injury
An observational study of Immune-Mediated Hepatitis, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
In this multi-center prospective observational study, the investigators plan to identify the incidence and risk factors for checkpoint inhibitor-induced liver injury and characterize biochemical, genetic, immunological, and histological features associated with it. 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?
- Obtaining biological samples
- How many people
- 160 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 Oct 2020to 30 Jun 2026
- 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: Adults with cancer receiving checkpoint inhibitors (CTLA-4, PD-1 or PD L1 inhibitor) as monotherapy or combination (without chemotherapy) and developed acute liver injury secondary to checkpoint inhibitor. Control Group: Patients with malignant melanoma, renal cell carcinoma, non-small cell lung cancer or any other cancer, receiving single or combination therapy using checkpoint inhibitors (CPIs).
Who may be able to join
- Both patient groups and control group:
- Able to give written informed consent OR Potential participants who have developed encephalopathy related to ChILI as a response to checkpoint inhibitor therapy, who lack the capacity to give written informed consent and have a consultee (personal or nominated) - for ChILI patient group only
- ChILI group:
- Patients who developed checkpoint inhibitor-induced liver injury and meet the following criteria:
- Meets one of the following analytical thresholds at enrolment (visit 1)
- Alanine transaminase (ALT) exceeding 5 times the upper limit of normal (ULN) OR
Show all 12Show fewer
- ALT exceeding 3 times ULN plus bilirubin exceeding 2 times ULN OR
- Alkaline phosphatase (ALP) exceeding 2 times ULN with accompanying elevations of gamma-glutamyl transferase in the absence of known bone metastases driving the rise in ALP level
- Absence of other known causes of liver injury after detailed investigations
- Patients who developed ChILI but did not meet the above criteria at enrolment or who were found to have a different cause for their liver injury after further investigations will be excluded from the analysis
- Control group:
- Consecutive patients with cancer who have a clinical indication to start checkpoint inhibitors. A small proportion of patients will develop ChILI following their checkpoint inhibitor treatment and will be classified as cases.
Who cannot join
- Patients who are treated with cytotoxic chemotherapy concurrently with checkpoint inhibitors.
- On the judgment of chief investigator that the person has certain alternative explanations to the acute event (rather than ChILI).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Edmond Atallah, M.D, MRCP(UK) contact
United Kingdom1 site, 1 recruiting
- Recruiting
University of Nottingham
Nottingham, NG72RD
Kim Byrne, bb-sponsor@exmail.nottingham.ac.uk
Edmond Atallah, M.D, MRCP(UK)
About this study
Official title: Checkpoint Inhibitor-induced Liver Injury Study (ChILI)
In this multi-center prospective observational study, the investigators plan to identify the incidence and risk factors for checkpoint inhibitor-induced liver injury and characterize biochemical, genetic, immunological, and histological features associated with it.
Read the detailed description
Checkpoint inhibitor-induced liver injury (ChILI) is a new incompletely understood category of hepatotoxicity which is distinct from other types of drug-induced liver injury (DILI) such as direct or idiosyncratic DILI. The data regarding the incidence and risk factors is lacking. Therefore, 'in-depth phenotyping' together with data from the control group exposed to checkpoint inhibitors (CPI) is necessary to develop refined algorithms incorporating CPI-related factors, host genetic and environmental risk factors that would enable pre-empting ChILI.
The aim of the study is to enroll two deeply phenotyped cohorts (patients who developed ChILI and patients who are starting checkpoint inhibitors) and obtain biological samples at multiple time points.
- Conditions
- Immune-Mediated Hepatitis
- Being tested
- Obtaining biological samples
- Keywords
- Immune checkpoints inhibitors, Immune-related adverse events, Hepatotoxicity, Liver injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Obtaining biological samplesDiagnostic test
Biological samples (blood, urine, stool). Liver tissue will be obtained from ChILI group when clinically indicated
| Study group | Role | What they receive |
|---|---|---|
| ChILI | Patients who are already on CPI therapy and have developed liver injury Receives: Diagnostic Test: Obtaining biological samples | |
| Control | Patients with cancer who are starting on checkpoint inhibitors Receives: Diagnostic Test: Obtaining biological samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of checkpoint inhibitor-induced liver injury (ChILI) and other immune-mediated adverse reactions
Measured: 3 years
Identify novel biomarkers associated with the diagnosis of ChILI
The investigators plan assessment of proposed circulating biomarkers including cytokines, microRNAs (miR-122, miR-4270 and miR-4463), total cytokeratin 18 (K18), macrophage colony-stimulating factor receptor (MCSFR), and any others identified in subsequent publications and measure their diagnostic and prognostic accuracy using the area under the receiver operating curve (AUROC).
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2020
- Study start13 Oct 2020
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Immune-Mediated HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04476563
- Sponsor's protocol ID
- 20034
- Acronym
- ChILI
- Status last verified
- Sep 2025
- First submitted
- 2 Jul 2020
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ji C, Kumpf S, Qian J, Federspiel JD, Sheehan M, Capunitan D, Atallah E, Astbury S, Arat S, Oziolor E, Ocana MF, Ramaiah SK, Grove J, Aithal GP, Lanz TA. Transcriptomic and proteomic characterization of cell and protein biomarkers of checkpoint inhibitor-induced liver injury. Cancer Immunol Immunother. 2025 May 3;74(6):190. doi: 10.1007/s00262-025-04033-z.
PubMed 40317333
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Checkpoint Inhibitor-induced Liver Injury Study (ChILI)
- ClinicalTrials.gov ID
- NCT04476563
- Acronym / sponsor ID
- ChILI / 20034
- Conditions
- Immune-Mediated Hepatitis
- Keywords
- Immune checkpoints inhibitors, Immune-related adverse events, Hepatotoxicity, Liver injury
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 13 Oct 2020 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 20 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this multi-center prospective observational study, the investigators plan to identify the incidence and risk factors for checkpoint inhibitor-induced liver injury and characterize biochemical, genetic, immunological, and histological features associated with it.
Detailed description
Checkpoint inhibitor-induced liver injury (ChILI) is a new incompletely understood category of hepatotoxicity which is distinct from other types of drug-induced liver injury (DILI) such as direct or idiosyncratic DILI. The data regarding the incidence and risk factors is lacking. Therefore, 'in-depth phenotyping' together with data from the control group exposed to checkpoint inhibitors (CPI) is necessary to develop refined algorithms incorporating CPI-related factors, host genetic and environmental risk factors that would enable pre-empting ChILI.
The aim of the study is to enroll two deeply phenotyped cohorts (patients who developed ChILI and patients who are starting checkpoint inhibitors) and obtain biological samples at multiple time points.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ChILI | – | Diagnostic Test: Obtaining biological samplesPatients who are already on CPI therapy and have developed liver injury |
| Control | – | Diagnostic Test: Obtaining biological samplesPatients with cancer who are starting on checkpoint inhibitors |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- ChILI group: Adults with cancer receiving checkpoint inhibitors (CTLA-4, PD-1 or PD L1 inhibitor) as monotherapy or combination (without chemotherapy) and developed acute liver injury secondary to checkpoint inhibitor. Control Group: Patients with malignant melanoma, renal cell carcinoma, non-small cell lung cancer or any other cancer, receiving single or combination therapy using checkpoint inhibitors (CPIs).
Key inclusion criteria (12 listed)
- Able to give written informed consent OR Potential participants who have developed encephalopathy related to ChILI as a response to checkpoint inhibitor therapy, who lack the capacity to give written informed consent and have a consultee (personal or nominated) - for ChILI patient group only
- Patients who developed checkpoint inhibitor-induced liver injury and meet the following criteria:
- Meets one of the following analytical thresholds at enrolment (visit 1)
- Absence of other known causes of liver injury after detailed investigations
- Patients who developed ChILI but did not meet the above criteria at enrolment or who were found to have a different cause for their liver injury after further investigations will be excluded from the analysis
Key exclusion criteria (2 listed)
- Patients who are treated with cytotoxic chemotherapy concurrently with checkpoint inhibitors.
- On the judgment of chief investigator that the person has certain alternative explanations to the acute event (rather than ChILI).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Obtaining biological samplesBiological samples (blood, urine, stool). Liver tissue will be obtained from ChILI group when clinically indicated | Diagnostic test | ChILI, Control |
Primary outcome
Incidence of checkpoint inhibitor-induced liver injury (ChILI) and other immune-mediated adverse reactions
Time frame: 3 years
Identify novel biomarkers associated with the diagnosis of ChILI
Time frame: 3 years
The investigators plan assessment of proposed circulating biomarkers including cytokines, microRNAs (miR-122, miR-4270 and miR-4463), total cytokeratin 18 (K18), macrophage colony-stimulating factor receptor (MCSFR), and any others identified in subsequent publications and measure their diagnostic and prognostic accuracy using the area under the receiver operating curve (AUROC).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2026.
- Derived from this study: PubMed 40317333Ji C, Kumpf S, Qian J, Federspiel JD, Sheehan M, Capunitan D, Atallah E, Astbury S, Arat S, Oziolor E, Ocana MF, Ramaiah SK, Grove J, Aithal GP, Lanz TA. Transcriptomic and proteomic characterization of cell and protein biomarkers of checkpoint inhibitor-induced liver injury. Cancer Immunol Immunother. 2025 May 3;74(6):190. doi: 10.1007/s00262-025-04033-z.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Edmond Atallah, M.D, MRCP(UK) contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Immune-Mediated Hepatitis, run by University of Nottingham at 1 site in United Kingdom.
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 12 inclusion and 2 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 24 Mar 2026. 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 United Kingdom. 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 Guruprasad Padur Aithal, MBBS, FRCP, PhD (0115 823 1074, guru.aithal@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of checkpoint inhibitor-induced liver injury (ChILI) and other immune-mediated adverse reactions (time frame: 3 years). The study lists 2 primary outcomes in all. 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 NCT04476563, which also lists 1 linked publication.
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 24 Mar 2026.