Characterization of Immune Semaphorin in Non Alcoholic Fatty Liver Disease and NASH

Study Overview
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Brief Summary
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Recent epidemiological studies in France showed a high prevalence of obesity (14.5%) and its strong increase in the last 20 years. Among the many complications associated with obesity, liver complications (steatosis and steatohepatitis [NASH]) are among the most common. Semaphorins were described in the early 1990. More than 20 types of these proteins have been reported to date. These proteins were used for neural development. Since many functions have also been described. The semaphorins are involved in numerous physiological or physiopathological processes (cardiac morphogenesis, vascular growth, tumor progression), the regulation of immune cells and liver fibrosis. Preliminary studies have allowed to show that dendritic cells infiltrate adipose tissue and initiate the activation of T cells and inflammation. Immune semaphorin are new players in the regulation of inflammation and immune reactions. The role of immune semaphorin in regulating inflammation in the two compartments (liver and adipose tissue) could be a crucial step that could lead to more severe liver damage. Its dysregulation could explain NASH injuries. The goal is to identify a new mode of regulation of cellular homeostasis in the fatty liver disease. These factors may serve as diagnostic markers or future therapeutic targets.

Official Title
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Characterization of Immune Semaphorin in Non Alcoholic Fatty Liver Disease and NASH

Conditions
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Non Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Other: Evaluation of the staging of fibrosis liver
* Other: Determine the expression level of semaphorin
* Other: Determination of the composition of immunity cells


Participation Criteria
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Eligibility Criteria
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Morbid obese patients Inclusion Criteria: Male and female aged 18-65 years Patients with body mass index justifying a surgery for obesity (BMI ≥ 40 kg / m2 or BMI ≥ 35 kg / m2 with comorbidities) Consumption of alcohol <20 g / d Patients affiliated to a social security insurance Patients who signed the informed consent Exclusion Criteria: Hemochromatosis Toxic hepatitis Deficiency of alpha-1-antitrypsin Wilson's disease Liver Autoimmune disease (primary biliary cirrhosis, autoimmune hepatitis) Hepatitis B, C Drug-induced hepatitis Presence of HIV status Corticosteroids, amiodarone, valproic acid, tamoxifen, anti-inflammatory drugs, lipid lowering agents, testosterone agonists or beta-adrenergic antagonists, orlistat. Pregnant or breastfeeding women Incarcerated patients or patient 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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Morbid obese patients<br> | Other: Evaluation of the staging of fibrosis liver<br>* The investigators will determine the severity of steatosis, inflammation and fibrosis by histological study of liver biopsies<br>Other: Determine the expression level of semaphorin<br>* The investigators will determine the expression level (gene and protein) of immune semaphorin and their (s) receptor (s) in the liver and subcutaneous and visceral adipose tissue by RT-PCR,<br>Other: Determination of the composition of immunity cells<br>* The investigators determine the composition of immunity cells by immunohistochemical and biochemical analyses (Western Blotting )<br>|
| Other: Control patients<br> | Other: Evaluation of the staging of fibrosis liver<br>* The investigators will determine the severity of steatosis, inflammation and fibrosis by histological study of liver biopsies<br>Other: Determine the expression level of semaphorin<br>* The investigators will determine the expression level (gene and protein) of immune semaphorin and their (s) receptor (s) in the liver and subcutaneous and visceral adipose tissue by RT-PCR,<br>Other: Determination of the composition of immunity cells<br>* The investigators determine the composition of immunity cells by immunohistochemical and biochemical analyses (Western Blotting )<br>|
| Other: Patients with overweight, steatosis and steatohepatitis<br> | Other: Evaluation of the staging of fibrosis liver<br>* The investigators will determine the severity of steatosis, inflammation and fibrosis by histological study of liver biopsies<br>Other: Determine the expression level of semaphorin<br>* The investigators will determine the expression level (gene and protein) of immune semaphorin and their (s) receptor (s) in the liver and subcutaneous and visceral adipose tissue by RT-PCR,<br>Other: Determination of the composition of immunity cells<br>* The investigators determine the composition of immunity cells by immunohistochemical and biochemical analyses (Western Blotting )<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the staging of liver fibrosis | The investigators determine the stage of liver fibrosis by histological study of biopsies | Day 0 | 
| Determination of the expression of level of semaphorin | The investigators determine by technic of Reverse Transcription Polymerase Chain Reaction (RT-PCR) the expression of level of semaphorin | Day 0 | 
| Determination of the composition of immunity cells | The investigators determine the composition of immunity cells by Immunohistochemical and biochemical analyses (Western Blotting) | Day 0 |