Study of Genetic Determinants in Alcoholic Hepatitis and Establishment of a Multicenter Prospective Cohort of Patients With Alcoholic Liver Disease

Recruiting

• Conditions: Severe Alcoholic Hepatitis; Alcoholic Cirrhosis; Alcoholic Liver Disease

• Registration Number: NCT04106518
• Lead Sponsor: University Hospital, Lille

Brief Summary

Alcoholic hepatitis carries a risk of high mortality at short term, especially in its severe form. Its diagnosis is confirmed by liver biopsy. The prevalence of alcoholic hepatitis, severe or not severe, is poorly known and prospective data are needed. The present observational study aims to define the prevalence of alcoholic hepatitis among patients admitted for jaundice and determine their outcome according to the severity. Survival and markers of liver dysfunction will be assessed. A biobank including genetic samples will be created to identify the disease profile in terms of inflammation and regeneration. The performance of non-invasive criteria for diagnosis will also be studied.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-27
• Study First Submitted QC: 2019-09-24
• Study First Posted: 2019-09-27
• Study Start: 2019-10-23
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-11-29
• Primary Completion: 2025-04
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 447

Inclusion Criteria

For SAH group:

• Alcohol consumption :

  • On average> 40 g / day for women and 50 g / day for men
  • Duration:> 5 years

• Recent jaundice episode (less than 3 months)

• Bilirubin> 50 mg / l (85μmol / l)

For NSAH group:

• Alcohol consumption :

• On average> 40 g / day for women and 50 g / day for men
• Duration:> 5 years

For cirrhosis (control) group:

• Alcohol consumption :

  • On average> 40 g / day for women and 50 g / day for men
  • Duration:> 5 years

• Unambiguous presence of cirrhosis criteria, including:

  • clinical signs (ascites, stellar angiomas ...) and / or
  • radiological signs (scanner or MRI: signs of hepatic dysmorphism and / or portal hypertension) and / or
  • biological signs (increased INR, thrombocytopenia) and / or
  • endoscopic signs (oesophageal / gastric varices)

Exclusion Criteria

For NAH and NSAH groups:

• Presence of another hepatic pathology: evidenced by blood biology, imaging or histology (viral or autoimmune hepatitis, hemochromatosis, Wilson's disease)
• Presence of hepatocellular carcinoma
• HIV infection

For cirrhosis (control) group:

• History established / suggestive of HAA (Clinical, biological and / or histological criteria) in particular absence of jaundice episode
• Presence of another hepatic pathology: evidenced by blood biology, imaging or histology (viral or autoimmune hepatitis, hemochromatosis, Wilson's disease)
• Presence of hepatocellular carcinoma
• HIV infection

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Prevalence of alcoholic hepatitis in heavy drinkers with jaundice	At baseline (time of liver biopsy)	Assess the prevalence of biopsy-proven alcoholic hepatitis in a cohort of heavy drinkers admitted with recent jaundice

Secondary Outcome Measures

Name	Time	Method
Survival	at 12 months	Survival rate at 12 months
Measurement of diagnostic performance (area under the ROC curve)	At baseline	Measurement of diagnostic performance (area under the ROC curve) of the simple and non-invasive clinical and biological criteria for alcoholic hepatitis proposed in an international expert opinion
Change in serum total bilirubin	Baseline, at 7 days, at 30 days, at 3 months at 6 months and at 12 months	Total bilirubin is a liver parameter, used for the biological liver test evaluation, measured in mg/dl in the serum
Change in serum creatinine	Baseline, at 7 days, at 30 days, at 3 months at 6 months and at 12 months	Creatinine is a marker of kidney function, assessed in the blood and measured in milligrams per deciliter
Change in MELD (Model for End-stage Liver Disease)score	Baseline, at 7 days, at 30 days, at 3 months at 6 months and at 12 months	The MELD score is a validated tool based on INR, creatinine and bilirubin measured in the blood with the following formula:(9.57 × log creatinine in milligrams per deciliter) + (3.78 × log bilirubin in milligrams per deciliter) + (11.20 × log international normalized ratio) + 6.43. The MELD score is used in liver disorders to assess the degree of liver failure. It has no unit.
Identification of inflammatory and biochemical profiles of patients with severe, non-severe and cirrhotic alcoholic hepatitis, based on the constitution of a biobank (serum and plasma)	Baseline, at 7 days, at 30 days and at 12 months	Serum and plasma evaluation of translational markers (e.g. cytokines) associated with inflammation in patients with alcohol-related liver disease. The list of markers which will be assessed cannot be determined at present and will depend on other ongoing studies performed in alcoholic hepatitis.
Identification of the genetic profiles of individuals with severe, non-severe and cirrhotic alcoholic hepatitis( blood sample)	Baseline	Evaluation of genetic markers associated with alcoholic hepatitis as compared to patients with alcohol-related liver disease without alcoholic hepatitis. We will use a non a priori approach as recommended in genetic studies. Thus, the list of genetic markers cannot be provided at that time.

Trial Locations

Locations (9)

Hôpital Jean Verdier, AH-HP; 🇫🇷 Bondy, France

Chr Angers; 🇫🇷 Angers, France

Chru Besancon; 🇫🇷 Besançon, France

Centre Hospitalier Universitaire; 🇫🇷 Caen, France

Chu Montpellier; 🇫🇷 Montpellier, France

Hopital Nord - Chu38 - La Tronche; 🇫🇷 La Tronche, France

Hôpital Claude Huriez, CHU; 🇫🇷 Lille, France

Association Hopital Saint Joseph - Marseille; 🇫🇷 Marseille, France

Hu Est Parisien Site St Antoine Aphp - Paris 12; 🇫🇷 Paris, France