Identification of Biomarkers Related to Liver Fibrosis as New Therapeutic Targets

Completed

• Conditions: Fibrosis; Hepatopathy
• Interventions: Other: Blood draw and liver resection

• Registration Number: NCT03979417
• Lead Sponsor: Institut Pasteur

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-04-10
• Study First Submitted QC: 2019-06-05
• Study First Posted: 2019-06-07
• Study Start: 2019-09-30
• Status Verified: 2022-03
• Primary Completion: 2022-09-01
• Study Completion: 2022-10-26
• Last Update Submitted: 2022-10-27
• Last Update Posted: 2022-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Liver fibrosis F2-F3	Blood draw and liver resection	Blood draw and liver resection at the liver surgery
Liver fibrosis F0-F1	Blood draw and liver resection	Blood draw and liver resection at the liver surgery
Liver Fibrosis F4	Blood draw and liver resection	Blood draw and liver resection at the liver surgery

Primary Outcome Measures

Name	Time	Method
Identification of biomarkers of liver fibrosis	Baseline	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.

Secondary Outcome Measures

Name	Time	Method
Evaluation of anti-fibrotic properties of biomarkers	Baseline	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.
Transcription factors	Baseline	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.

Trial Locations

Locations (2)

Pitie-Salpetriere Hospital; 🇫🇷 Paris, France

Cochin Hospital; 🇫🇷 Paris, France