# Immunological Profiles and prognostic outcomes in patients with alcoholic hepatitis

> **NIH NIH U01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $211,548

## Abstract

Project Summary
Alcoholic hepatitis is a leading cause of morbidity and mortality in the US. Despites its complicated
pathogenesis, one of the key drivers in the disease process is the alterations in the innate and adaptive immune
responses secondary to excessive alcohol use. This application is in response to the funding opportunity
“Alcoholic hepatitis clinical and translational network – translational research (RFA-AA-18-003)”. The goal
of our application is to better understand the role and mechanism of innate and adaptive immunity in the
pathogenesis of alcoholic hepatitis, as this may help us identify novel therapeutic targets to treat this severe
form of ALD. Two specific aims are proposed: Aim# 1: Determine the impact and prognostic significance of
microbial translocation, immune dysregulation on the disease severity and outcomes in patients with AH. In
this aim, we hypothesized that (i) the state of immune dysregulation has the impact on baseline disease
severity and long term outcome of patients with AH and (ii) persistent immune activation during the follow
up despite abstinence is adversely affected outcomes of patients with AH. We found that ethanol primes
peripheral blood mononuclear cells for LPS-induced inflammatory responses. In sub-aim#1.1, we will perform
a detail cross sectional/longitudinal analysis on baseline gut permeability, microbial translocation, immune cell
activation/inflammation in healthy controls, ED without liver diseases, and those with AH. We also found that
plasma IL-8, a potent chemokine for neutrophils, were markedly elevated in patients with AH. The induction
of neutrophils leads to hepatic inflammation/injury with the release of mitochrondrial-DNA containing
microparticles (MPs) from the hepatocytes; perpetuating neutrophilia and liver injury. In sub-aim#1.2, we will
determine the role and clinical significance of IL-8 and mitochrondrial-DNA (mt-DNA) in patients with AH.
Aim#2: Determine the mechanism and significance of alteration in follicular helper T cells in patients with
AH. Little is known about how alcohol affects the adaptive immune system, despite the increase risk of
infections among those with excessive alcohol use. Follicular T helper (TFH) cells are a CD4 T cell lineage
uniquely found in the germinal center reaction of secondary lymphoid organs. The specific function of TFH
cells is to select B cells in the germinal center that produce high-affinity Abs. Our novel preliminary data
showed, for the first time, on the effect of excessive drinking and ALD on circulating TFH (cTFH) cells. In this
aim, we hypothesized that excessive alcohol consumption leads to altered cTFH cell differentiation, and that
these effects on cTFH cells are augmented and impacted survival outcomes in patients with AH. We will test
that (i) AH patients have dysregulation of cTFH cells, (ii) AH patients have T cell-intrinsic or T cell-extrinsic
defects that alter cTFH cell differentiation, and, and (iii) AH patients have ...

## Key facts

- **NIH application ID:** 10190739
- **Project number:** 5U01AA026917-04
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Suthat Liangpunsakul
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $211,548
- **Award type:** 5
- **Project period:** 2018-09-22 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190739

## Citation

> US National Institutes of Health, RePORTER application 10190739, Immunological Profiles and prognostic outcomes in patients with alcoholic hepatitis (5U01AA026917-04). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10190739. Licensed CC0.

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