# Systematic Analysis and Threshold Synthesis for |G*| as a Diagnostic Biomarker for NAFLD and NASH Clinical Trials - DDT-BMQ-000099

> **NIH FDA U01** · MAYO CLINIC ROCHESTER · 2021 · $250,000

## Abstract

Higher incidence of metabolic disease and obesity have fueled a rise in non-alcoholic fatty liver
disease (NAFLD), which has in turn contributed to increased prevalence of non-alcoholic
steatohepatitis (NASH). Despite the increasing prevalence of NAFLD and NASH, drug
development in this area has faced several challenges – notably the lack of validated,
noninvasive biomarkers to enroll patients based on the stage of fibrosis. This is a critical
enrollment step, as regulatory bodies have identified two specific cohorts of NASH patients for
clinical study: NASH with fibrosis (F2-F3) and NASH with cirrhosis (F4). A validated diagnostic
biomarker for enrolling subjects in the correct cohort of interest in a timely and cost-effective
way would replace the need for liver biopsy and greatly propel the field forward.
The overall goal of this work is to document an evidence base to support the use of an MR
elastography-based measurement of the magnitude of the complex shear modulus (|G*|) as a
diagnostic pre-screening biomarker. |G*| is proposed for use to screen for subjects with
NAFLD/NASH with high risk of having histopathologic findings of significant fibrosis. This
biomarker has an accepted Letter of Intent (DDTBMQ000099).
While |G*| and its corresponding measurement method, magnetic resonance elastography
(MRE), is recognized as a reliable and established biomarker of liver fibrosis in the clinical
radiology and hepatology communities, there are minor gaps that must be filled for this
diagnostic Context of Use. The objective for this proposal is to conduct a retrospective analysis
of the diagnostic performance of this biomarker for staging liver fibrosis and to establish
standardized thresholds for |G*| for use as a diagnostic screening drug development tool.
Aim 1: Establish cutoffs for |G*| for the diagnosis of significant (≥F2), advanced fibrosis (≥F3) or
cirrhosis (F4) for subjects with NAFLD and determine evidence-based diagnostic performance
summaries of |G*| compared with the reference standard of liver biopsy for a pre-screening
context of use.
Aim 2: Validate optimal cutoffs in a test cohort of subjects with NAFLD and biopsy determine
the diagnostic performance (sensitivity, specificity, PPV, NVP, and AUROC).
The completion of Aim 1 and Aim 2 will provide critical evidence to further the development of
|G*| as a pre-screening biomarker for fibrotic NAFLD/NASH, fulfilling an unmet need in NAFLD
drug development. Completion of this work will inform our Qualification Plan for |G*| as a pre-
screening biomarker to the FDA’s Biomarker Qualification Program.

## Key facts

- **NIH application ID:** 10410011
- **Project number:** 1U01FD007472-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Kay Marie Pepin
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2021
- **Award amount:** $250,000
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10410011

## Citation

> US National Institutes of Health, RePORTER application 10410011, Systematic Analysis and Threshold Synthesis for |G*| as a Diagnostic Biomarker for NAFLD and NASH Clinical Trials - DDT-BMQ-000099 (1U01FD007472-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10410011. Licensed CC0.

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