# Alcoholic Hepatitis Consortia: an intramural/extramural collaboration to unravel genetic determinants

> **NIH NIH U01** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $351,527

## Abstract

PROJECT SUMMARY/ABSTRACT
18 million Americans abuse alcohol, with alcoholic liver disease (ALD) affecting over 10 million people. Alcohol
abuse's deleterious effects on the liver leads to pathologically distinct entities including steatosis,
steatohepatitis, fibrosis and cirrhosis; patients can develop alcoholic hepatitis (AH) at any time in the
progression of disease. AH is the most severe form of ALD and only occurs in a sub-set of heavy drinkers,
suggesting a role for genetic and environmental risk factors. AH is a particularly costly presentation of ALD;
treatment costs are estimated to be ~$40K per patient with average length of stay in hospital lasting 6-9 days.
While the standard therapy for severe AH is glucocorticoids, many patients are steroid-resistant; steroid-
resistant patients have a 6 month mortality rate greater than 45%. Also of critical importance, there is no
currently approved treatment for patients with moderate AH; 28 day mortality in moderate AH is ~10-15%.
NIAAA recognized the great need to develop rationally-based therapies of AH and established the Alcoholic
Hepatitis Consortia (ASH UO1) in 2012/2013, funding four independent consortia to conduct clinical and
translational studies in patients with moderate to severe alcoholic hepatitis. While each consortia developed
independent clinical approaches, the collection of genetic material, as well as an extensive phenotypic analysis
of all patients, was a common theme amongst the four groups. We are now combining the efforts of all 4
consortia in order to leverage these critical biospecimens and clinical data into a single cohort large enough for
investigations into the genetic contributions to AH. In order to carry out a thorough genetic analysis, here we
propose an extramural/intramural collaboration (PAR-16-104 Program for Extramural/ Intramural Alcohol
Research Collaborations (U01)) with Dr. David Goldman in the Laboratory of Neuro Genetics (LNG) at NIAAA.
Dr. Goldman and his team have extensive expertise in whole exome sequencing and analysis of allele
frequencies related to alcohol abuse. The combination of the extensive biorepository and phenotypic data
from the ASH UO1 consortia with the expertise of the intramural LNG uniquely qualifies our team to identify
critical genetic components leading to AH, as well as the sensitivity to therapeutic intervention. Identification
of specific genetic components will likely provide insights into why only a subset of patients who abuse alcohol
develop AH and identify potential druggable molecular drivers. Here we propose to carry out the following
Specific Aims: 1) Whole exome sequencing of the DNA from ~1000 patients with AH, as well as a cohort of
heavy drinking controls without liver disease and 2) Novel analytical approaches to determine genetic risk for
key determinants of AH including a) Susceptibility for developing AH among heavy drinkers, b) Risk for early
mortality from AH, c) Response to therapy and d) Alcohol Recidivi...

## Key facts

- **NIH application ID:** 10246294
- **Project number:** 5U01AA026264-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Jaideep Behari
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $351,527
- **Award type:** 5
- **Project period:** 2017-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246294

## Citation

> US National Institutes of Health, RePORTER application 10246294, Alcoholic Hepatitis Consortia: an intramural/extramural collaboration to unravel genetic determinants (5U01AA026264-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246294. Licensed CC0.

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