Comparison of Inflammatory Profiles and Regenerative Potential in Alcoholic Liver Disease (TargetOH)
Primary Purpose
Liver Diseases, Acute on Chronic Hepatic Failure
Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
collection of liver biopsies collection of blood samples
Sponsored by
About this trial
This is an interventional basic science trial for Liver Diseases
Eligibility Criteria
Inclusion Criteria:
- group A: patients with acute alcoholic hepatitis
- Active alcohol abuse defined by DSM IV and excessive alcohol consumption prior to admission (> 60 g per day for men and> 40 g per day for women)
- Moderate elevation of transaminases (less than 500 U / L) with a typical ASAT / ALAT ratio of 2: 1
- Bilirubin> 50 mg / l
- Absence of autoimmune liver disease (ANA <1/80, AML <1/80, LKM1 neg, AAM neg)
- Absence of hepatitis B and C and HIV infection (negative anti-HIV antibodies, negative HBsAg, negative HCV PCR)
- Patients with other acute complications than alcoholic hepatitis may be included (eg, digestive hemorrhage, acute renal failure, infection, etc.)
- Because there is no validated noninvasive tool for the diagnosis of alcoholic hepatitis, histological confirmation is required in all patients (preferably by transjugular biopsy): alcoholic hepatitis will be diagnosed on the presence of the following histological characteristics: Hepatocellular lesions (ballooning, Mallory body)/ Inflammatory infiltrate with polymorphonuclear neutrophils
- group B1: patients with alcoholic cirrhosis
- Decompensated or non-decompensated alcoholic cirrhosis, defined according to the HAS guidelines, ie by a liver biopsy or a cluster of clinico-biological arguments (www.has-sante.fr)
- group B2: patients free from chronic liver disease
- Justification of blood and liver sampling for the management of a pathology other than chronic liver disease (eg liver metastasis of digestive cancer occurring on healthy liver)
Exclusion Criteria:
- For groups A and B1:
- Patients with hepatocellular carcinoma of progressive non-hepatic cancer
- Presence of HBsAg
- Presence of anti-HCV antibodies by positive PCR
- Presence of antibodies to HIV 1 +2
- Pregnancy
- for group B2:
- Alcoholic liver disease
- Presence of HBsAg
- Presence of anti-HCV antibodies by positive PCR
- Presence of antibodies to HIV 1 +2
- Pregnancy
Sites / Locations
- Hôpital Claude Huriez, CHRURecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Other
Other
Other
Arm Label
acute alcoholic hepatitis
Alcoholic cirrhosis
Without chronic liver disease
Arm Description
collection of liver biopsies collection of blood samples in patients with acute alcoholic hepatitis (group A)
collection of liver biopsies collection of blood samples in patients with alcoholic cirrhosis (group B1)
collection of liver biopsies collection of blood samples in patients without chronic liver disease (group B2)
Outcomes
Primary Outcome Measures
the expression of proinflammatory cytokines
Proinflammatory Cytokines (TNF, IL-1, IL-6, IL-8)
Secondary Outcome Measures
the expression of genetic variants of pro-inflammatory cytokines
Identification of genetic variants of pro-inflammatory cytokines that contribute to mortality of Alcoholic Liver Disease
Cell lysis (AST, ALT, CK18 cleaved)
Regeneration markers (Ki-67, Fn14, CK7)
Full Information
NCT ID
NCT03773887
First Posted
October 16, 2018
Last Updated
January 6, 2021
Sponsor
University Hospital, Lille
1. Study Identification
Unique Protocol Identification Number
NCT03773887
Brief Title
Comparison of Inflammatory Profiles and Regenerative Potential in Alcoholic Liver Disease
Acronym
TargetOH
Official Title
Comparison of Inflammatory Profiles and Regenerative Potential in Alcoholic Liver Disease
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Recruiting
Study Start Date
September 2015 (Actual)
Primary Completion Date
September 2027 (Anticipated)
Study Completion Date
September 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Lille
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main objective of this study is the comparison of the profile of the pro-inflammatory cytokines at the patients suffering from an alcoholic hepatitis to that of two groups witnesses: patients suffering from an alcoholic cirrhosis and unhurt patients of chronic liver disease
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Diseases, Acute on Chronic Hepatic Failure
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
450 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
acute alcoholic hepatitis
Arm Type
Other
Arm Description
collection of liver biopsies collection of blood samples in patients with acute alcoholic hepatitis (group A)
Arm Title
Alcoholic cirrhosis
Arm Type
Other
Arm Description
collection of liver biopsies collection of blood samples in patients with alcoholic cirrhosis (group B1)
Arm Title
Without chronic liver disease
Arm Type
Other
Arm Description
collection of liver biopsies collection of blood samples in patients without chronic liver disease (group B2)
Intervention Type
Other
Intervention Name(s)
collection of liver biopsies collection of blood samples
Intervention Description
blood and ascites samples; extraction of explants, hepatic resection parts; hepatic parenchyma on liver biopsies
Primary Outcome Measure Information:
Title
the expression of proinflammatory cytokines
Description
Proinflammatory Cytokines (TNF, IL-1, IL-6, IL-8)
Time Frame
Baseline
Secondary Outcome Measure Information:
Title
the expression of genetic variants of pro-inflammatory cytokines
Description
Identification of genetic variants of pro-inflammatory cytokines that contribute to mortality of Alcoholic Liver Disease
Time Frame
Baseline
Title
Cell lysis (AST, ALT, CK18 cleaved)
Time Frame
Baseline
Title
Regeneration markers (Ki-67, Fn14, CK7)
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
group A: patients with acute alcoholic hepatitis
Active alcohol abuse defined by DSM IV and excessive alcohol consumption prior to admission (> 60 g per day for men and> 40 g per day for women)
Moderate elevation of transaminases (less than 500 U / L) with a typical ASAT / ALAT ratio of 2: 1
Bilirubin> 50 mg / l
Absence of autoimmune liver disease (ANA <1/80, AML <1/80, LKM1 neg, AAM neg)
Absence of hepatitis B and C and HIV infection (negative anti-HIV antibodies, negative HBsAg, negative HCV PCR)
Patients with other acute complications than alcoholic hepatitis may be included (eg, digestive hemorrhage, acute renal failure, infection, etc.)
Because there is no validated noninvasive tool for the diagnosis of alcoholic hepatitis, histological confirmation is required in all patients (preferably by transjugular biopsy): alcoholic hepatitis will be diagnosed on the presence of the following histological characteristics: Hepatocellular lesions (ballooning, Mallory body)/ Inflammatory infiltrate with polymorphonuclear neutrophils
group B1: patients with alcoholic cirrhosis
Decompensated or non-decompensated alcoholic cirrhosis, defined according to the HAS guidelines, ie by a liver biopsy or a cluster of clinico-biological arguments (www.has-sante.fr)
group B2: patients free from chronic liver disease
Justification of blood and liver sampling for the management of a pathology other than chronic liver disease (eg liver metastasis of digestive cancer occurring on healthy liver)
Exclusion Criteria:
For groups A and B1:
Patients with hepatocellular carcinoma of progressive non-hepatic cancer
Presence of HBsAg
Presence of anti-HCV antibodies by positive PCR
Presence of antibodies to HIV 1 +2
Pregnancy
for group B2:
Alcoholic liver disease
Presence of HBsAg
Presence of anti-HCV antibodies by positive PCR
Presence of antibodies to HIV 1 +2
Pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Philippe Mathurin, MD,PhD
Phone
03 20 44 55 97
Ext
+33
Email
philippe.mathurin@chru-lille.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philppe Mathurin, MD,PhD
Organizational Affiliation
University Hospital, Lille
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Claude Huriez, CHRU
City
Lille
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe Mathruin, MD,PhD
First Name & Middle Initial & Last Name & Degree
Alexandre Louvet, MD,PhD
12. IPD Sharing Statement
Learn more about this trial
Comparison of Inflammatory Profiles and Regenerative Potential in Alcoholic Liver Disease
We'll reach out to this number within 24 hrs