Adipose Tissue Involvement in Alcohol-induced Liver Inflammation in Human

NCT00388323 | Completed

• 2 other identifiers: P 051041AOR 05049
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

The histological characteristics of alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH) related to overweight and obesity suggest the presence of partly common physiopathological mechanisms. We reported that the ponderal overload was an independent risk factor of alcoholic cirrhosis. The adipose tissue was considered for a long time as a simple place of storage of fat. However, it is now recognized that the adipose tissue can secrete cytokines called ADIPOKINES. The adipose tissue can secrete others cytokines such as TNF-alpha, IL6, IL10 and IL1-Ra. Increase in the production of the leptin and TNF-alpha by the adipose tissue after alcohol administration in the rat, as well as the role of leptin in inflammation and liver fibrogenesis in the murine model of chemical hepatotoxicity strongly suggest that activation of adipocytes by alcohol can explain the strong correlation observed between the body mass index (BMI) and the severity of ethanol-induced liver injury. Conversely, it was suggested in a murine model that the reduction in adiponectin production would sensitize the liver with the toxicity of alcohol. The PPAR alpha and gamma are the receptors which play a role both in inflammation and glucide and lipid metabolism. Taking into account the inhibiting role of PPAR alpha on the proliferation of the hepatic stellate cells, responsible for the fibrosis, the PPAR could also be implied in the relation between the overweight and the hepatic fibrosis in the alcoholic.

Conditions

Alcoholic Hepatitis; Alcoholic Cirrhosis

Keywords

Alcohol; Hepatitis; Cirrhosis; Inflammation; Cytokines; ADIPOKINES; Adipose tissue

Outcome Measures

Primary Outcomes (2)

• Adipokines

  To demonstrate that ADIPOKINES are implied in the intensity of the steatosis and in the regulation of the inflammatory process and the hepatic fibrogenesis in alcoholic liver disease.

  at the inclusion and after one week

• PPAR α et γ

  To demonstrate that the PPAR α et γ are implied in the intensity of the steatosis and in the regulation of the inflammatory process and the hepatic fibrogenesis in alcoholic liver disease.

  At the inclusion and after one week

Study Arms (1)

1

EXPERIMENTAL

Other: blood and biopsies

Interventions

blood and biopsies OTHER

blood and biopsies

1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Alcoholic patients of both sex aged from 18 to 75, hospitalized for alcoholic liver disease.
• HBs antigen negative, HIV negative, anti -VHC negative
• daily consumption exceeded 40-50 grams per day during the last year
• elevated AST level and liver biopsy during the hospitalisation Patients who signed the informed consent document
• patients affiliated to the national health insurance system

You may not qualify if:

• patients having another cause than alcohol for liver injury
• hepatocellular carcinoma or another developing cancer, severe associated pathology (cardiac disease, respiratory insufficiency, severe psychiatric problems), pancreatitis, infection, diabetes or a dyslipidemia
• patients treated with fibrates or other hypolipidaemic drugs, oral antidiabetics or insulin
• patients having hemostasis which does not permit the TRANSCOSTAL liver biopsy, platelet level \<60 giga/l, or Quick test \< 50 %, or (TCA higher than 1,5 times the time of the witness)
• patients refuse an adipose tissue biopsy
• patients treated with long-duration dose of clopidogrel (Plavix®)
• patients not-affiliated to the national health insurance system

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Antoine Béclère

Clamart, 92140, France

Location

Related Publications (1)

• Voican CS, Njike-Nakseu M, Boujedidi H, Barri-Ova N, Bouchet-Delbos L, Agostini H, Maitre S, Prevot S, Cassard-Doulcier AM, Naveau S, Perlemuter G. Alcohol withdrawal alleviates adipose tissue inflammation in patients with alcoholic liver disease. Liver Int. 2015 Mar;35(3):967-78. doi: 10.1111/liv.12575. Epub 2014 Jun 3.

  PMID: 24766056 DERIVED

MeSH Terms

Conditions

Hepatitis, Alcoholic; Liver Cirrhosis, Alcoholic; Hepatitis; Fibrosis; Inflammation

Interventions

Blood Specimen Collection; Biopsy

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Liver Cirrhosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical

Study Officials

• Gabriel PERLEMUTER, MD

  Hôpital Antoine Béclère - Clamart - FRANCE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2006
• First Posted: October 16, 2006
• Study Start: November 1, 2006
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: December 11, 2012

Record last verified: 2012-11

Locations

FR (1)