# Predicting outcomes in nonalcoholic steatohepatitis with advanced fibrosis

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $634,480

## Abstract

Hepatic decompensation (overt ascites, encephalopathy and variceal hemorrhage) and mortality in patients with
nonalcoholic steatohepatitis (NASH) increases exponentially with the development of cirrhosis. Prevention of
such liver-associated clinical events (LACE) is therefore a major goal of therapeutics. This requires identification
of those at risk and targeting them with effective therapeutics. Current approaches to identify this population
include the use of fibrosis markers such as FIB4, liver-stiffness measurement (LSM), assessment of hepatic
venous pressure gradient and/or varices (endoscopy) and traditional measures of liver function. These are
unfortunately limited by modest accuracy of some models, retrospective, single center nature of most data-sets
published and lack of information on the impact of changes in these parameters over time with respect to dynamic
changes in risk profile. This proposal innovates by novel application and integration of systemic, hepatic
perfusion and function, and portal hypertension related parameters to holistically model the risk of LACE and
generate a probability score that is sensitive to change. We will specifically focus on MRI-based measures of
systemic metabolic dysfunction (metabo-phenotype), gadoxetate uptake and clearance (integrated measure of
hepatic perfusion and clearance function) and spleen stiffness measurement (SSM) as a surrogate for portal
hypertension. We further propose the novel hypothesis that holistic models including these measures and
capturing the multi-factorial origin of hepatic decompensation events are superior to conventional tools used in
routine practice to define the probability of LACE in patients with compensated cirrhosis due to NASH. The
hypothesis will be tested in a longitudinal cohort study of compensated cirrhosis due to NASH. The specific
measures of the metabo-phenotype will include visceral adipose tissue volume, fat-free muscle volume, muscle
fat infiltration. Gadoxetate uptake and clearance will be measured in a 10-minute exam. The SSM probe was
recently approved and will be deployed on Fibroscan 630 the flagship instrument for transient elastography.
Metabo-phenotyping requires implementing an imaging protocol, based on a routine clinical imaging sequence,
onto standard clinical scanners which adds less than 10 minutes of scan-time while gadoxetate is routinely used
for liver-imaging. Sub-aim 1 will model baseline parameters, alone and in combination, to define outcome risk
within 1-2 years. Sub-aim 2 will evaluate dynamic changes in values of the test measures over time and relate
them to changes in the risk of outcomes. Both regression and machine learned approaches will be taken to
generate probability scores of the outcomes. Sensitivity analyses will be performed to test the robustness of the
models. The patient populations needed and all of the methods/expertise are available. The rationale of this
proposal is that it will provide a method for risk-i...

## Key facts

- **NIH application ID:** 10446281
- **Project number:** 1R01DK129564-01A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** ARUN J SANYAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $634,480
- **Award type:** 1
- **Project period:** 2022-09-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446281

## Citation

> US National Institutes of Health, RePORTER application 10446281, Predicting outcomes in nonalcoholic steatohepatitis with advanced fibrosis (1R01DK129564-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10446281. Licensed CC0.

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