Identification of Biomarkers Related to Liver Fibrosis as New Therapeutic Targets (FIBROTHER)

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.

Study Overview

• Status: Completed
• Conditions: Fibrosis; Hepatopathy
• Intervention / Treatment: Other: Blood draw and liver resection

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 Type: Observational
• Enrollment (Actual): 14

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Cochin Hospital
  • Paris, France, 75013
    • Pitié-Salpêtrière Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with primary hepatopathies or liver metastasis with indication for liver resection.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Liver fibrosis F0-F1; Blood draw and liver resection at the liver surgery	Other: Blood draw and liver resection; The samples are transferred to the research unit for immunological studies.
Liver fibrosis F2-F3; Blood draw and liver resection at the liver surgery	Other: Blood draw and liver resection; The samples are transferred to the research unit for immunological studies.
Liver Fibrosis F4; Blood draw and liver resection at the liver surgery	Other: Blood draw and liver resection; The samples are transferred to the research unit for immunological studies.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut Pasteur

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): October 26, 2022

Study Registration Dates

• First Submitted: April 10, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 7, 2019

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Biomarkers
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: 2018-069

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No