Integrated Approaches for Identifying Molecular Targets in Alcoholic Hepatitis

The development of new targeted therapies for alcoholic hepatitis (AH) is one of the more urgent needs in clinical hepatology. To reach this goal, large multidisciplinary networks are required. The proposed initiative "Integrated Approaches for Identifying Molecular Targets in Alcoholic Hepatitis" (InTeam) will coordinate a multidisciplinary group composed of clinicians, physician-scientists, basic scientists and bioinformatics experts. The overarching hypothesis of InTeam is that the most rational way to provide a useful framework for future clinical trials in (AH) consists of the (i) determination of key drivers of the disease process, (ii) classification of molecular profiles and subtypes of AH, and (iii) identification of "druggable" targets based on both key drivers and molecular classification. Moreover, mouse models for AH are lacking making it impossible to evaluate promising targets in preclinical mouse studies in a meaningful manner. For this purpose, InTeam will integrate data obtained from molecular pathology studies in human AH and functional studies of key pathways in animal models. The proposed InTeam consortium includes three research projects, ten clinical centers, a Human Biorepository and a Mouse Models Core. The Human Biorepository Core will generate the to-date largest collection of samples from patients with AH from 10 academic liver centers and a comprehensive database that will serve as a basis for the proposed translational studies and be a valuable asset for the broader scientific community. The Mouse Models core will conduct murine studies after establishing and evaluating mouse models of AH based on the pathophysiology and molecular drivers of human AH determined by this consortium.

Inclusion criteria

• Patients 18 ≥ and ≤ 70 years of age.
• Active alcohol abuse within the past 3 months.
• Has an Aspartate Aminotransferase (AST) > Alanine Aminotransferase (ALT).
• Elevated Total Bilirubin level > 3.0.
• Absence of autoimmune liver disease (ANA>1/320).
• Absence of hepatitis B infection.
• A liver biopsy, and/or a clinical picture consistent with alcoholic hepatitis.
• The "Start Date" (is the date of the liver biopsy or ≤ to 1 week [72 hours is preferred] from the time of admission).

Exclusion criteria

• Hepatocellular carcinoma.
• Complete portal vein thrombosis.
• Advanced or terminal extrahepatic diseases.
• Lack of consent to participate in the study.
• Pregnancy.
• Received more than 3 days of treatment with (prednisolone or pentoxifyllin) prior to start date.

Control patients