Integrated Therapies for Alcohol use in Alcohol-associated Liver Disease (ITAALD) - Virginia Commonwealth University

Severe alcohol-associated hepatitis (sAH) has high short-term mortality, yet it currently has no FDA-approved therapy. Although return to drinking impacts quality of life and mortality in these patients, available pharmacological treatments and behavioral therapies have not been widely utilized in the care of this patient population. An optimal approach would involve the care integration of both alcohol-associated liver disease (ALD) and alcohol use disorder (AUD). Our combined team of experts in AUD and ALD seeks to overcome the perceived stigma of alcohol misuse, which can adversely affect treatment seeking, quality of care, and patient outcomes Our overall hypothesis is that an integrated management of ALD and AUD will improve clinical outcomes in patients with sAH. Aim 1. In the current study, we propose a sequential, multiple assignment, randomized trial to assess the safety and efficacy of integrated therapies in sAH. The integrated intervention includes a novel IL-22 fusion protein, compared to daily prednisone for 28 days with a Day-7 Lille stopping rule; survivors of the first 7 days will be re-randomized to either acamprosate, followed by a motivational interview (MI), and sessions of motivational enhancement therapy (MET), compared to usual care for AUD. Acamprosate is among the safest FDA-approved therapies for AUD, but its efficacy has not been evaluated for sAH. A composite measure of mortality, liver, and alcohol use outcomes at 6 months will be the primary endpoint. Aim 2. Build a platform for biosamples, data repositories, and patient registries to support site-specific and networkwide ancillary studies. These proposed studies will leverage the existing resources of AlcHepNet to evaluate the clinical impact of integrated ALD/AUD treatment in a diverse cohort of patients.