Study of Alcohol-related Liver Disease in Europe

NCT ID: NCT04400604

Last Updated: 2022-03-17

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 7500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-03-03
• Study Completion Date: 2032-03-31

Brief Summary

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.

Conditions

Alcoholic Liver Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

1: Patients with minimal risk of extensive fibrosis

TE \< 5.8kPa; rule out cut-off value)

No interventions assigned to this group

2: Patients with intermediate risk of fibrosis

No interventions assigned to this group

Patients with high risk of extensive fibrosis

No interventions assigned to this group

Patients with compensated cirrhosis biopsy-proven

No interventions assigned to this group

Patients with a first decompensation

patients with a first decompensation event of cirrhosis after exclusion of HCC.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Active alcohol excessive consumption defined as > 210 g per week for men and> 140 g per week for women during the previous year.
• Patients with high risk of alcoholic-related liver disease can be included only if the following assessment were available: Abdominal Ultrasound / Ultrasound elastography pulse (FibroScan®) / FibroTest®, AshTest® and LCR1-LCR2® (cost will be supported by Biopredictive) / Non-patented methods: Forns Index; Fib-4, Hepascore®/ Absolute values should be provided for all these methods.

For patient in whom liver stiffness measurements were uninterpretable (unavailable results) only those with FibroTest® and LCR1 and LCR2 measurements can be included.

Results of FibroScan® were considered unavailable based on following criteria: When no value was obtained after at least 10 shots (valid shot=0) OR If SR (Success Rate), the ratio of valid shots to the total number of shots at least 60% OR IQR (InterQuartil Range reflecting variability of measurements) less than 30% of the median LSM (Liver Stiffness Measure) value (IQR≤LSM≤30%).

• Patients must provide written informed consent and agree to have blood stored for the study and tissue stored for those in whom physicians performed liver biopsy according their clinical practice.
• Patients should agree to participate for at least 5-year follow-up.
• Patients with social insurance

Exclusion Criteria

• Evidence of other forms of known chronic liver disease including:Positive test result at baseline for hepatitis B surface antigen or positive serology of hepatitis C virus infection (regardless PCR results)/ Autoimmune liver disease / Known or suspected HCC
• Any previous episode of decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding before current hospitalization and/or inclusion in the study
• Known positivity for human immunodeficiency virus infection.
• Terminal extrahepatic illness defined as: All conditions evolved into a clinical stage to limit the patient's functional status (e.g.: heart failure, renal failure, neurological or respiratory diseases, or any other disabling diseases etc. …).
• Other medical conditions that may diminish life expectancy to <2 years.
• Known extra-hepatic cancers with the exception of basal cell skin cancer.
• Any other condition that, in the opinion of the Investigator, would impede completion of the study (eg: Homeless, non-compliant patients…).
• Mental instability or incompetence, such that the validity of informed consent is uncertain.
• Lack of informed consent or refusal to participate for follow up evaluation.
• A condition in which repeated blood draws pose more than minimal risk for the subject such as hemophilia, other severe coagulation disorders or significantly impaired venous access.
• Pregnant or lactating women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe Mathurin, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Lille

Locations

Hop Claude Huriez Chu Lille

Lille, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Philippe Mathurin, MD,PhD

Role: CONTACT

philippe.mathurin@chru-lille.fr

3 20 44 55 97 ext. +33

Facility Contacts

Role: primary

0320445962

Other Identifiers

2020-A00527-32

Identifier Type: OTHER

Identifier Source: secondary_id

2019_04

Identifier Type: -

Identifier Source: org_study_id