Fibroscan® Medical Device, Assessment for Non Invasive Diagnosis of Liver Steatosis

Study Overview
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Brief Summary
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Hypothesis of this study is the existence of a relation between parameters measured by FibroScan® FS 502 according to our non invasive method and liver steatosis condition. This proof of concept validation is made up of two steps: Step 1: feasibility study of the method on 10 healthy volunteers Step 2: diagnosis study on 50 healthy volunteers (25 between 18-30 years-old and 25 between 40-65 years-old) and on 25 patients whom cares including an liver biopsy et whom the histological answer is clean steatosis (NAFLD). Experimental procedures consist in: Fibroscan measure, preceded by tracking ultrasonography. liver MRI (for substudy about MRI comparison, in step 2) a blood test for biological assessment of liver functions

Detailed Description
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Diagnosis of liver lipid overload (named liver steatosis), unrelated to alcohol consumption, still mainly based on histological exam of the liver. An histological continuity exists going from clean liver steatosis (Non Alcoholic Fatty Liver Disease, NAFLD) to steatohepatitis with signs of inflammation and tissue fibrosis (Non Alcoholic Steato-Hepatitis, NASH). It's now well-known that disease can evolve to cirrhosis and its complications. Hypothesis of this study is the existence of a relation between parameters measured by FibroScan® FS 502 according to our non invasive method and liver steatosis condition. This proof of concept validation is made up of two steps: Step 1: feasibility study of the method on 10 healthy volunteers Step 2: diagnosis study on 50 healthy volunteers (25 between 18-30 years-old and 25 between 40-65 years-old) and on 25 patients whom cares including an liver biopsy et whom the histological answer is clean steatosis (NAFLD). Measures on healthy volunteers enable to do an intra-operator reproductibility analysis, a study of an age effect and a search of potential mechanic aging of the liver. Experimental procedures consist in: Fibroscan measure, preceded by tracking ultrasonography. liver MRI (for substudy about MRI comparison, in step 2) a blood test for biological assessment of liver functions The final aim of this study is to propose a device enable medical community to do in vivo hepatic rheology observation, highly correlated to liver lipid overload. After industrialization of this innovation, this diffusion could making easier patients follow-up.

Official Title
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Fibroscan® Medical Device, Assessment for Non Invasive Diagnosis of Liver Steatosis

Conditions
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Liver Steatosis

Intervention / Treatment
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* Device: Fibroscan
* Biological: Blood test for biological assessment of liver function
* Device: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects - Steps 1 and 2 Age between 18 and 65 years old (2 age groups for step 2 : 18-30 et 40-65 years-old) Written inform consent form signed Affiliated to medical insurance Alcohol consumption d'alcool < 20g/j for women, <30g/j for men Patients with liver steatosis - Step 2 More than 18 years -old Written inform consent form signed Affiliated to medical insurance Patients with clean steatosis confirmed by histological results of a liver biopsy done the previous month Alcohol consumption d'alcool < 20g/j for women, <30g/j for men Exclusion Criteria: Healthy subjects - Step 1 Exposure to chemical poisons (solvents, paints, drugs) in the previous 4 weeks Pregnant women, lactating women, and women in age for procreation and without reliable contraception Presence of ascites Person under guardianship Healthy subjects - Step 2 Exposure to chemical poisons (solvents, paints, drugs) in the previous 4 weeks Pregnant women, lactating women, and women in age for procreation and without reliable contraception Contraindication to MRI Presence of ascites Person under guardianship Healthy subjects - Steps 1 and 2 Presence of liver tumor or ascites (diagnosed with MRI or ultrasonography) Abnormal liver function tests (increase of transaminases, gammaGT) Patients with liver steatosis - Step 2 Exposure to chemical poisons (solvents, paints, drugs) in the previous 4 weeks Pregnant women, lactating women, and women in age for procreation and without reliable contraception Contraindication to MRI Presence of ascites liver tumor Serology anti VHC+ or Ag HBs+ Infection by HIV Auto-immun hepatitis Genetic hemochromatosis, Wilson disease, lake of alpha-1-antitrypsin Fibrosis or liver cirrhosis at biopsy Person under guardianship

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fibroscan exam<br>Step 1: feasibility study of the method on 10 healthy volunteers Step 2: diagnosis study on 50 healthy volunteers (25 between 18-30 years-old and 25 between 40-65 years-old) and on 25 patients whom cares including an hepatic biopsy et whom the histological answer is clean steatosis (NAFLD). Experimental procedures consist in: Fibroscan measure, preceded by tracking sonography. liver MRI (for substudy about MRI comparison, in step 2) a blood test for biological assessment of liver functions | Device: Fibroscan<br>* Three series oh independent measures Measure done with Fibroscan will be preceded by tracking ultrasonography.<br>Biological: Blood test for biological assessment of liver function<br>* Blood test for biological assessment of liver function<br>Device: MRI<br>* Liver MRI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viscosity in Pa.s | Digital files recorded by medical device will be mathematically processed for extracting elasticity G' and viscosity G'' curves in accordance with the frequency. These curves use to identify the 5 parameters: mu(M), eta(M), alpha, mu(V), eta(V); which describe visco-elasticity variations with frequency thanks to an Matlab algorithm | One day | 
| Elasticity in kPa | Digital files recorded by medical device will be mathematically processed for extracting elasticity G' and viscosity G'' curves in accordance with the frequency. These curves use to identify the 5 parameters: mu(M), eta(M), alpha, mu(V), eta(V); which describe visco-elasticity variations with frequency thanks to an Matlab algorithm | One day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reproductibility quantification in arbitrary unit | The 5 estimated parameters (which describe visco-elasticity) will be used to quantify the medical device reproductibility | through study completion, an average of 2 years | 
| Age in years | The 5 estimated parameters (which describe visco-elasticity) and the age oh the healthy volunteers wil be used to study an age effect | through study completion, an average of 2 years | 
| Liver signal intensity changes in decibel | Adiposis charge will be assessed by measure of liver signal intensity decrease on T1 sequence in phase opposition compared to in phase signal, after correction by iron quantity | through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver steatosis, Steatohepatitis, Fibroscan