Integrated Therapies for Alcohol use in Alcohol-associated Liver Disease (ITAALD)- Cleveland Clinic Clinical Center

Cleveland Clinic Lerner Com-Cwru, Cleveland OH

Investigators

Linked publications & trials

Abstract

Alcohol-associated liver disease (ALD) is a leading cause of liver-related mortality/morbidity, and there is no FDA-approved therapy for any stage of ALD. Advanced ALD conditions, including severe alcohol-associated hepatitis (sAH) have especially poor outcomes. Indeed, the 90-day mortality for sAH is ~30%. Return to drinking impacts quality of life, morbidity and mortality in these patients. There are limited drug therapies or well-studied behavior therapies in this patient population. An optimal approach would be the integration of AUD and ASLD care givers and therapies, but there are no guidelines for this approach. Our proposed AUD/ALD team approach seeks to overcome the perceived stigma of alcohol misuse which can adversely affect treatment seeking, quality of care and patient outcomes. The AlcHepNet RCT was stopped at the interim analysis because of the unexpected 90% 90-day survival in sAH patients treated with prednisone using the Lille stopping rule. These dramatic results need to be confirmed, and novel therapies such as IL-22 need to be studied in sAH. Acamprosate appears to be the safest FDA-approved therapy for AUD in patients with ALD, but safety and efficacy in severe ALD need to be evaluated. Motivational interviewing/enhancement therapy is well-suited behavioral therapy for patients with ALD. Based on preliminary data and knowledge gaps, our overall hypothesis is that integrated management of ALD and AUD will improve clinical outcomes in patients with sAH and decompensated ALD. We will utilize the following AIMS: Aim 1. Perform a randomized controlled trial of treatment for steroid-eligible patients with severe AH. A SMART trial design will be used to compare daily prednisone for 28 days (with the 7-day Lille score-based stopping rule) vs IL-22 fusion protein (F-652) followed by randomization of each of these groups to receive motivational Interviewing/enhancement therapy combined with acamprosate vs usual care including referral to 12-step programs before discharge from the hospital. The primary endpoint of the trial will be a composite measure of mortality, liver, and alcohol use related outcomes at 6 months. AIM 2. Build a platform for biosamples, data repositories, and patient registries to support site-specific and network-wide ancillary studies. In summary, these proposed studies will leverage the existing resources of the AlcHepNet to evaluate the clinical impact of integrated ALD/AUD treatment in a cohort of patients for whom there are limited treatment options.