Project Details
Description
PROJECT SUMMARY/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) and decompensated alcohol-associated cirrhosis (deAC), have especially poor outcomes.
Indeed, the 90-day mortality for sAH is ~30%. Return to drinking impacts quality of life 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 study
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. Treatment with Lactobacillus rhamnosus GG (LGG) improved MELD score
at 30 days and reduced drinking at 6 months in patients with moderate AH (e.g., novel AUD/ALD therapy).
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. Take Control is a novel computer-based behavioral platform derived
from the NIAAA’s Rethinking Drinking which we propose to evaluate in severe ALD. Based on preliminary data
and knowledge gaps, our overall hypothesis is that an 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 double-blind randomized controlled trial of treatment for steroid-eligible patients with
severe AH. A masked study comparing daily prednisone for 28 days (with the 7-day Lille score-based stop rule)
vs. IL-22 fusion protein (F-652). Early intervention for AUD will include behavioral therapy platform (Take Control)
in all subjects and either acamprosate or placebo before discharge from the hospital. The primary endpoint of
the trial will be a composite measure of mortality, liver, and alcohol use related outcomes. Aim 2. Evaluate
Lactobacillus rhamnosus GG (LGG) in patients with decompensated ALD cirrhosis. In patients with
decompensated cirrhosis due to ALD, in whom corticosteroids are not effective, a randomized, placebo-
controlled trial of LGG in combination with Take Control and locally accepted SOC for 6 months will be performed.
A composite measure (as in Aim 1) at 6 months will be the primary end point for this AIM also. Aim 3. Build a
platform for biosamples, data repositories, and patient registries to support site-specific and
networkwide 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 diverse cohort of typically
underserved patients.
Status | Active |
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Effective start/end date | 8/1/18 → 6/30/25 |
Funding
- National Institute on Alcohol Abuse and Alcoholism: $355,080.00
- National Institute on Alcohol Abuse and Alcoholism: $369,000.00
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