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

Centre Hospitalier Universitaire de Nice

Status: Completed

Conditions: Non Alcoholic Fatty Liver Disease

Treatments: Other: Determine the expression level of semaphorin; Other: Determination of the composition of immunity cells; Other: Evaluation of the staging of fibrosis liver

Study type: Interventional

Funder types: Other

Identifiers

NCT02820285

11-PP-10

Details and patient eligibility

About

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.

Enrollment: 148 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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148 participants in 3 patient groups

Morbid obese patients

Other group

Treatment:

Other: Evaluation of the staging of fibrosis liver

Other: Determine the expression level of semaphorin

Other: Determination of the composition of immunity cells

Control patients

Other group

Treatment:

Other: Evaluation of the staging of fibrosis liver

Other: Determine the expression level of semaphorin

Other: Determination of the composition of immunity cells

Patients with overweight, steatosis and steatohepatitis

Other group

Treatment:

Other: Evaluation of the staging of fibrosis liver

Other: Determine the expression level of semaphorin

Other: Determination of the composition of immunity cells