Therapies for patients with alcoholic hepatitis have not changed over the past 30 years with corticosteroid treatment being the only established pharmacologic treatment.

However, only some patients benefit from this therapy and the mortality for patients with this disease remains high. There is an urgent clinical need to identify new therapeutic targets and develop clinically applicable therapies for patients with alcoholic hepatitis. To reach this goal, we have built InTeam, a large international consortium composed of highly specialized liver centers, to investigate key druggable pathways.

The overarching hypothesis of this consortium is that the most rational way to provide a useful framework for future clinical trials in alcoholic hepatitis consists of the identification of potentially “druggable” molecules and identifying the most appropriate target by matching them to the prevailing molecular profile of each patient. For this purpose, InTeam will integrate data obtained from functional studies in animal models and molecular pathology studies in humans. Developing this model will involve the combined effort of multiple research laboratories and clinical centers.

To accomplish these goals, the focus of the consortium will surround three scientific projects.

Project #1: “Molecular Subtypes for Targeted Therapies in Alcoholic Hepatitis”

Principal investigators: Ramon Bataller, MD, PhD & Philippe Mathurin, MD, PhD

In this project, the investigators will develop a molecular classification of alcoholic hepatitis in order to favor personalized medicine so each patient receives the most appropriate targeted therapy. Moreover, we want to identify the mechanisms of liver failure in these patients.

Project #2: “Targeting DAMPs in Alcoholic Hepatitis”

Principal Investigators: Robert Schwabe, MD, PhD & Wajahat Mehal, MD, PhD

In this project, the investigators will assess the role of internal molecules that are released by the damaged liver and activate the innate immune system. These molecules are called DAMPS and represent potential targets for new therapies.

Project #3: “Microbiota as Therapeutic Targets in Alcoholic Hepatitis”

PrincipaI Investigators: Bernd Schnabl, MD & David Brenner, MD

This project will investigate the role of bacterial products derived from the gut (PAMPs) in the pathogenesis of alcoholic hepatitis. Most importantly, we will investigate in animal models if therapies that modify our microbiome have therapeutic potential in this disease.

Supporting Cores:

The InTeam consortium will utilize an Administrative Core to handle all organizational aspects of the consortium and ensure proper communication among the different sites. In addition, the Consortium has a Human Biorepository Core to obtain and analyze all biospecimens and deindentified clinical data as well as a Mouse Models Core (directed by Ivan Rusyn, MD, PhD) to optimize a model of alcoholic hepatitis for use in preclinical studies.

We expect that the information generated within InTeam to guide successful future clinical trials capable of improving the outcomes of this severe medical condition.