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

Alcoholic Liver Disease Clinical Trial

— COMADHAA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04106518
• Other study ID #: 2017_51
• Secondary ID: 2018-A02286-49
• Status: Recruiting
• Start date: October 23, 2019
• Est. completion date: April 2025

Study information

• Verified date: November 2023
• Source: University Hospital, Lille
• Contact: Alexandre Louvet, MD,PhD
• Phone: 03 20 44 55 97
• Email: alexandre.louvet[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 447
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alcoholic Cirrhosis
• Alcoholic Liver Disease
• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic
• Liver Cirrhosis, Alcoholic
• Liver Diseases
• Liver Diseases, Alcoholic
• Severe Alcoholic Hepatitis

Locations

Country	Name	City	State
France	Chr Angers	Angers
France	Chru Besancon	Besançon
France	Hôpital Jean Verdier, AH-HP	Bondy
France	Centre Hospitalier Universitaire	Caen
France	Hopital Nord - Chu38 - La Tronche	La Tronche
France	Hôpital Claude Huriez, CHU	Lille
France	Association Hopital Saint Joseph - Marseille	Marseille
France	Chu Montpellier	Montpellier
France	Hu Est Parisien Site St Antoine Aphp - Paris 12	Paris

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of alcoholic hepatitis in heavy drinkers with jaundice	Assess the prevalence of biopsy-proven alcoholic hepatitis in a cohort of heavy drinkers admitted with recent jaundice	At baseline (time of liver biopsy)
Secondary	Survival	Survival rate at 12 months	at 12 months
Secondary	Change in serum total bilirubin	Total bilirubin is a liver parameter, used for the biological liver test evaluation, measured in mg/dl in the serum	Baseline, at 7 days, at 30 days, at 3 months at 6 months and at 12 months
Secondary	Change in serum creatinine	Creatinine is a marker of kidney function, assessed in the blood and measured in milligrams per deciliter	Baseline, at 7 days, at 30 days, at 3 months at 6 months and at 12 months
Secondary	Change in MELD (Model for End-stage Liver Disease)score	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.	Baseline, at 7 days, at 30 days, at 3 months at 6 months and at 12 months
Secondary	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)	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.	Baseline, at 7 days, at 30 days and at 12 months
Secondary	Identification of the genetic profiles of individuals with severe, non-severe and cirrhotic alcoholic hepatitis( blood sample)	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.	Baseline
Secondary	Measurement of diagnostic performance (area under the ROC curve)	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	At baseline