Kathy Jung, Ph.D.

February 09, 2023

Purpose

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) seeks to continue the Alcohol-associated hepatitis (AH) research program, a multi-center translational and clinical network (AlcHepNet), established in 2012 with renewal in 2018. The goal of AlcHepNet is to accelerate the discovery and validation of new diagnostic and treatment options for patients with severe AH.

The AH program achieved significant milestones and made remarkable progress in its scientific and programmatic objectives. Notable achievements include establishing consensus statements on disease definitions and common data elements, conducting impactful randomized clinical trial, and performing research studies that promote clinical trial readiness, such as natural history studies, biomarker identification and outcome measures development.

Background

AH is the most severe form of alcohol-associated liver disease prevalent in people with decades of heavy alcohol use, for which there is no FDA-approved treatments. 

The cultural attitude and beliefs surrounding AH have shifted in recent years. There is growing recognition by hepatologists that AH patients suffer from two different disorders, alcohol use disorder (AUD) and liver disease, and both disorders need to be addressed.

The recent retrospective observational studies in AH reported that participating in alcohol rehabilitation was associated with 70%–84% lower risk of 30-day hospital readmission, 89%–91% lower risk of 30-day alcohol relapse, and 80% lower risk of long-term mortality. Still, less than 8% of AH patients received alcohol relapse prevention medication.

There is a clear need for a new treatment paradigm in AH that addresses not only the patients’ liver disease but also alcohol use. However, evidence for how to guide treatment decisions is lacking and current implementation strategies vary across healthcare delivery contexts.

Scope

The proposed research concept addresses the need to treat the co-morbidities of AUD and AH. It will leverage AlcHepNet resources and capabilities to conduct multi-center and multi-disciplinary clinical trials designed to assess safety and efficacy of interventions targeting both AUD and AH simultaneously under the same infrastructure.

In order to address gaps in the AH field, this renewal concept will:

• Provide evidence that active interventions for AUD will reduce liver-related mortality in patients with AH
• Provide evidence for practical approaches (treatment duration, endpoints, outcome measures, etc.) to conduct clinical trials that combine treatments for AUD and AH
• Promote collaboration between hepatology and addiction specialists
• Provide evidence about potential risks of drug-induced hepatotoxicity of medications for AUD in patients with AH

Justification/Outcome

Given the value of AlcHepNet resources and the maturation of the program, NIAAA proposes a concept that builds on the previous program successes and also responds to the needs of the hepatology field.  

The structure of the program will be tailored to the evolving knowledge and opportunities to advance NIAAA priorities and scientific community at large.

Several outcomes are expected, including conducting novel clinical trials that will overcome limitations of past, traditional, trial designs as well as providing critical progress in defining new and effective clinical management strategies for patients with severe AH.