# Extracellular Vesicles in Alcoholic Liver Disease: Basic and Pre-Clinical Discovery

> **NIH NIH UH3** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $433,391

## Abstract

ABSTRACT
Alcoholic hepatitis (AH) has high mortality and management of these patients is limited by the lack of reliable
markers of liver injury, inflammation and infection that determine clinical outcomes. Extracellular vesicles (EVs)
are novel biomarkers that are more sensitive compared to serum associated-biomarkers because of the
stability of biomolecules within the EVs. EVs contain characteristic RNA and protein cargo that can provide a
unique signature of disease. While characterization of these different EV populations is an emerging field, the
use of EVs as potential biomarkers is rapidly evolving in clinical applications. Our preliminary results suggest
that there is an increased number of EVs in AH and these EVs have distinct RNA, micro-RNA and protein
cargos compared to normal controls that indicate their potential for biomarker discovery. However, the features
of biology that distinguish heavy drinkers with no liver disease from those who present with alcoholic hepatitis
are unknown. In this application, we propose to take a two-step approach to study the EV cargo as a potential
biomarker in alcoholic hepatitis. The UH2 phase will focus on the discovery phase in two steps: first, to define
optimal approaches to EV isolation, RNA and protein sample preparation and, second, pilot proteomics and
transcriptome analyses that will identify potential biomarker candidates in alcoholic hepatitis compared to
normal controls (DASH samples). The second, UH3, phase will validate the proteomic and RNA-seq
characteristic of EVs from the UH2 phase now in a larger cohort of AH patients from the AlcHepNet
Observational study and compare those to heavy drinkers (HD) without liver disease (discovery). Proteomic
and RNA transcriptomic profiles of the 3 sets of well-characterized human cohorts will identify EV-associated
signatures of AH that is different from HD without liver disease and normal controls. Our study will further
discover correlations between unique signatures in the protein cargo and/or RNA transcriptome profile of EVs
that indicate survival and/or clinical outcomes in AH. The large dataset from these “omics” analyses will
establish a unique AH-proteomic-transcriptome interface (AH-PTI) and this will provide invaluable resources for
the AlcHepNet investigators and the entire alcohol research field for future hypothesis-driven studies.

## Key facts

- **NIH application ID:** 10440307
- **Project number:** 5UH3AA026970-06
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Gyongyi Szabo
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $433,391
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440307

## Citation

> US National Institutes of Health, RePORTER application 10440307, Extracellular Vesicles in Alcoholic Liver Disease: Basic and Pre-Clinical Discovery (5UH3AA026970-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440307. Licensed CC0.

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