Identification of Biomarkers Related to Liver Fibrosis as New Therapeutic Targets

Study Overview
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Brief Summary
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Fibrosis is a dynamic process resulting from the balance of fibrogenesis and fibrolysis, mainly secondary to chronic necro-inflammation related to regular alcohol consumption, metabolic syndrome (NASH) or viral hepatitis. The liver has the property of allowing the reversion of fibrosis / cirrhosis when the necrotic-inflammatory activity is controlled. The balance between fibrosis / fibrolysis and its inhibition depends on many pathways and the hypothesis of the efficacy of a single treatment remains uncertain. Molecular factors in the progression of liver fibrosis should be determined. It is necessary to control the liver fibrosis and thus reduce the risk of carcinoma in this population. The anti-fibrotic drugs are being developed, but so far only alpha-tocopherol and obeticholic acid have been shown to have a significant anti-fibrotic effect in humans. Several new drugs are currently being evaluated in ongoing Phase 2 and 3 randomized clinical trials, but most of them have intrinsic limitations: (i) they take a long time for evaluation (> 3 years), ( ii) they generally require an histopathological evaluation by serial liver biopsies that are invasive and unpopular with patients who are aware of noninvasive tests for fibrosis assessment and (iii) treatment is often a single treatment versus a placebo group with the uncertainty that at 1 or 3 years, serial liver biopsies results are convincing.

Detailed Description
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The study will be performed in 30 patients. Patients will be enrolled in two investigators sites (Cochin Hospital, Pitie-Salpetriere Hospital, France) where the patient selection will be conducted during a Multidisciplinary Collaborative Meeting. The patients will be enrolled after collecting their informed consent. As soon as the patient is included, arrangements will be made for the organization of the liver resection according to the usual procedure of the hospital department. The biological samples for the research (blood and liver) will be taken at the time of the surgery and sent to the Research Unit (Institut Pasteur) where immunological analyses will be carried out.

Official Title
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Identification of Biomarkers Related to Liver Fibrosis as New Therapeutic Targets

Conditions
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Hepatopathy, Fibrosis

Intervention / Treatment
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* Other: Blood draw and liver resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients > 18 years Patients with primary liver disease or liver metastases Patients undergoing liver resection Exclusion Criteria: Presence of Human Immunodeficiency Virus (HIV) infection Presence of Human T Leukemia Virus (HTLV) infection Taking immunosuppressive drugs in the 6 months prior to surgery A person deprived of liberty by judicial or administrative decision

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Liver fibrosis F0-F1<br>Blood draw and liver resection at the liver surgery | Other: Blood draw and liver resection<br>* The samples are transferred to the research unit for immunological studies.<br>|
| Liver fibrosis F2-F3<br>Blood draw and liver resection at the liver surgery | Other: Blood draw and liver resection<br>* The samples are transferred to the research unit for immunological studies.<br>|
| Liver Fibrosis F4<br>Blood draw and liver resection at the liver surgery | Other: Blood draw and liver resection<br>* The samples are transferred to the research unit for immunological studies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of biomarkers of liver fibrosis | Frequency of cell receptors (CD4, CD8, NK, MAIT, etc.) in whole blood and liver (measured by FACS). A comparison will be made in each of the 3 groups (F0-F1, F2-F3, F4) and between the three groups. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transcription factors | Frequency of transcription factors (Stat1, Stat3, Foxp3, etc.) in whole blood and liver (measured by FACS). A comparison will be made in each of the 3 groups (F0-F1, F2-F3, F4) and between the three groups. | Baseline | 
| Evaluation of anti-fibrotic properties of biomarkers | Monitoring the properties by different techniques (ELISA, Nanostring, Immunoblotting). A comparison will be made in each of the 3 groups (F0-F1, F2-F3, F4) and between the three groups. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarkers