# Exposome and Precision Medicine in NAFLD

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2021 · $614,249

## Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, and it is often associated with obesity
and metabolic disruption. NAFLD has a variable clinical course, and only some patients develop nonalcoholic
steatohepatitis (NASH) and progressive fibrosis which increase mortality. An environmental contribution to
NAFLD has previously been demonstrated by special exposure cohort studies and animal models. However,
data gaps prevent the clinical application of this emerging environmental health scientific knowledge to impact
the clinical care of NAFLD patients through a precision medicine approach. This project proposes a new, high-
impact, virtual consortium (the NAFLD-ViCTER) to conduct synergistic, multidisciplinary, translational
exposomics research in adult NAFLD patients to address these knowledge gaps. It tests the hypothesis that
environmental exposures contribute to NAFLD severity, natural history and response to therapy via hepatic
transcriptional reprogramming resulting in metabolic disruption. The consortium is composed of investigators
with synergistic expertise and resources from three centers including: Matt Cave (PI, University of Louisville),
Naga Chalasani (Co-I, Indiana University), and Dean Jones (Co-I, Emory University). The specific aims are: 1)
To determine the environmental exposures associated with adult NAFLD severity in a cross-sectional study. This
analytical cross-sectional study with internal comparisons utilizes previously collected, archived, de-identified
materials from adult patients with NAFLD characterized by vibration-controlled transient elastography and
histology. Untargeted high-resolution exposomics (HRE) will be performed in plasma. Sex differences will be
investigated. Exposome-wide association studies (EWAS) vs. NAFLD severity biomarkers will be performed. 2)
To elucidate the mechanisms by which environmental exposures increase the severity of NAFLD. This analytical
cross-sectional study utilizes materials from Aim 1 along with previously determined genotyping and hepatic
mRNA-SEQ data. Untargeted high-resolution metabolomics (HRM) will be performed in plasma. MWAS and
transcriptome wide association studies (TWAS) will be performed vs. (i) NAFLD severity biomarkers and (ii) the
exposures associated with NAFLD severity using data-driven integrative and pathway analyses. Gene:
environment interactions will be examined. 3) To determine the environmental chemicals associated with NASH
histologic progression and response to therapy in a longitudinal study. Archived de-identified data and plasma
specimens from a previously-published, multi-center, placebo-controlled clinical trial of obeticholic acid for adult
NASH will be utilized. Plasma HRE/HRM will be performed and the exposures/metabolic signatures associated
with NASH histologic progression and response to therapy will be determined using the placebo and obeticholic
acid treated patients, respectively. NAFLD-ViCTER will transform the clinic...

## Key facts

- **NIH application ID:** 10248534
- **Project number:** 5R01ES032189-02
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Matthew C Cave
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $614,249
- **Award type:** 5
- **Project period:** 2020-08-28 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248534

## Citation

> US National Institutes of Health, RePORTER application 10248534, Exposome and Precision Medicine in NAFLD (5R01ES032189-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10248534. Licensed CC0.

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