Alcohol-induced liver injury is made up of fatty liver, fibrosis and alcoholic hepatitis (AH), elementary lesions that may occur separately, simultaneously or sequentially in a same patient. Among these histological features, alcoholic hepatitis, a necro-inflammatory process is associated with the fastest fibrosis progression leading to cirrhosis in 40% of cases and a pivotal lesion driving increased risk of liver decompensation. The non-invasive methods for the diagnosis of fibrosis open new perspectives for a better understanding of the natural history of disease-progression from early injury to the cirrhotic stage, for the identification of subgroup patients at risk of developing cirrhosis at medium term and for proposing a strategy of screening of patients with extensive cirrhosis at risk of liver-threatening events. There is an urgent need to perform studies in asymptomatic heavy drinkers in order to identify cut-offs associated with significant risk of development of cirrhosis at medium term. Such objectives require large-scale screening of heavy drinkers. Each of non-invasive methods have been tested to predict with of extensive fibrosis with a high predictive performance as shown below. A screening policy cannot be accepted without answering the following questions: a) are the requirements of public health screening fulfilled? b) Is the group of patients undergoing screening defined? c) is there a reliable method for of testing? Indeed, the detection of a disease is subject to certain public health requirements and may be proposed to health authorities only if it modifies the management of subjects screened. In the specific case of mass screening of liver fibrosis in heavy drinkers, only the detection of extensive fibrosis could fulfill this criterion because of the potential survival benefit resulting from the screening of hepatocellular carcinoma (HCC) in patients with extensive fibrosis. Indeed, recent studies have found that the probability of receiving curative treatment of HCC was significantly higher in patients who received a six-month surveillance ultrasound. Therefore, the detection of extensive fibrosis seems reasonable in the light of these studies when considering that the yearly risk of development of HCC in the subgroup of heavy drinkers with extensive fibrosis is approximately 3%. Taking into account the above scientific arguments, the most recent EASL clinical practical guidelines on ALD recommend longitudinal studies using non-invasive tools to evaluate screening of extensive fibrosis and disease progression in heavy drinkers.
Study Type
OBSERVATIONAL
Enrollment
7,500
Hop Claude Huriez Chu Lille
Lille, France
RECRUITINGA first occurrence of clinical diagnosis of cirrhosis and/or its complications(for patients of group 1 and 2)
The primary endpoint is a composite criterion defined as a first occurrence of clinical diagnosis of cirrhosis and/or its complications. The primary endpoint will be held in the presence of any of the following criteria: Clinical cirrhosis Or Hepatocellular carcinoma (HCC) Or Histological diagnosis of cirrhosis on liver biopsy Or Biological features of liver dysfunction: INR≥1.5 in the presence of one of the following features: platelet count \<100 000, albumin \<35g, bilirubin \> 2\* ULN it will assess the risk of clinical diagnosis of cirrhosis and/or its complications in heavy drinkers classified according to non-invasive methods at minimal or intermediate risk of extensive fibrosis (groups 1,2).
Time frame: at five years
cumulative incidence of cirrhosis and/or complications by treating death as competing risk.(for patients of group 3)
measure the risk of clinical diagnosis of cirrhosis and/or its complications in heavy drinkers classified according to non-invasive methods at high risk of extensive fibrosis (group 3).
Time frame: at five years
All-cause of death
all-cause mortality in groups of heavy drinkers (Groups 1,2,3) and cirrhotic groups (Groups 4 et 5)
Time frame: at five years
Biobanking of liver tissue and blood samples for further analyses such as cirrhosis disease studies
A multi-national registry of liver tissue and blood samples (bio-bank collection) to get more insights in risk of development of cirrhosis and disease-progression of cirrhosis
Time frame: at five years
LCR1/LCR2 test
Measure the performance of LCR1 and LCR2 to predict risk of development of hepatocellular carcinoma (All Groups) LCR1 test combines (using Cox model) hepatoprotective proteins (apolipoproteinA1, haptoglobin) with known risk factors (gender, age, gamma-glutamyltranspeptidase), and a marker of fibrosis (alpha2-macroglobulin). To increase the specificity, the LCR2 test was developed by combining the components of LCR1 to alpha-fetoprotein. The predetermined cutoffs are \<0.015 for low-LCR1, and \<0.044 for low-LCR2 will be tested as the rule-out values to exclude a risk of hepatocellular carcinoma.
Time frame: at five years
Brief Drinking Questionnaire (Audit-C)
The AUDIT-C (Alcohol Use Disorder Identification Test) quantifies alcohol misuse, based on 3 questions posed to patients about their consumption habits. It was adapted from the first three questions of the AUDIT. The AUDIT-C is scored on a scale of 0-12 (scores of 0 reflect no alcohol use). Each question has 5 answer choice. In men, a score of 4 or more is considered positive; in women, a score of 3 or more is considered positive. Generally, the higher the AUDIT-C score, the more likely it is that the patient's drinking is affecting his/her health and safety.
Time frame: at five years
Alcohol consumption according to the WHO category
Patterns of alcohol consumption will be classified according the 5 risks levels (Abstinence, Low risk, Medium risk, high risk, very high risk).
Time frame: at five years
The occurrence of decompensation of cirrhosis
To determine the 5-year risk of first decompensation in patients with biopsy-proven compensated cirrhosis at inclusion (Group 4)
Time frame: at five years
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