# Biomarkers of Disease in Alcoholic Hepatitis

> **NIH NIH U01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $261,195

## Abstract

ABSTRACT
Alcoholic hepatitis (AH) is the most severe form of alcohol-induced organ damage in the liver with clinical
manifestations of severe liver disease and high mortality. The precipitating factors and determinants of clinical
outcome remain elusive in AH. The clinical outcome of AH depends on key factors such as 1) impaired host
defense in the alcoholic patient that predisposes to infections; 2) systemic inflammation in AH that contributes to
the development of Systemic Inflammatory Response Syndrome (SIRS) and multi-organ failure; and 3) the
regenerative capacity of the liver. In this proposal, we aim to answer critical questions related to these key
determinants of clinical outcomes using bedside to bench approaches. We will utilize biospecimens prospectively
collected in the AlcHepNet clinical trial in the observational study (Aim#1) to evaluate the functional, phenotypic
and metabolomics characteristics of major circulating immune cell populations in the well-defined patient
populations in this study: severe AH, moderate AH, heavy drinkers without evidence of clinical liver disease, and
normal control. Samples from the Late Stage Clinical Trial that include the treatment arms of prednisone, IL-
1receptor antagonist (IL-1ra, also known as anakinra, plus zinc) and G-CSF will be utilized to gain mechanistic
insights into these novel treatments through translational research. Because these interventions target elements
of inflammation, immune responses and/or liver regeneration, evaluation of the prospectively collected
biospecimens will provide a valuable tool for mechanistic ex vivo studies that complement the clinical
observations collected in the main clinical trial. The AlcHepNet clinical trial will collect clinical data on well-defined
patient and control populations linked with unique biospecimens to support high-quality translational research
and address some of the most burning clinical questions in AH. The Specific Aims are:
Aim #1: To assess alcohol-induced immunosuppression and dysregulated innate immune responses to
pathogen-derived signals in relation to the natural history, infections and clinical outcomes in patients
with AH using samples from the AlcHepNet Observational Study.
Aim #2: To test the biological consequences of novel therapies with IL-1ra and G-CSF on innate immune
activation, markers of gut leakiness and circulating markers of liver regeneration using prospectively
collected samples from the AlcHepNet Late Stage Clinical Trial.
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## Key facts

- **NIH application ID:** 10427324
- **Project number:** 5U01AA026933-06
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Gyongyi Szabo
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $261,195
- **Award type:** 5
- **Project period:** 2019-09-19 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427324

## Citation

> US National Institutes of Health, RePORTER application 10427324, Biomarkers of Disease in Alcoholic Hepatitis (5U01AA026933-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10427324. Licensed CC0.

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