Noninvasive Biomarkers of Metabolic Liver Disease 1.1

Noninvasive Biomarkers of Metabolic Liver Disease 1.1

NIMBLE is a comprehensive collaborative effort to standardize, compare, validate, and advance the regulatory qualification of imaging and circulating biomarkers to diagnose and stage nonalcoholic steatohepatitis (NASH), and to predict and assess response to therapeutic intervention (https://fnih.org/what-we-do/biomarkers-consortium/programs/nimble). This study focuses on estimating the repeatability and reproducibility of ultrasound elastography-based biomarkers across a range of fibrosis stages.

Study 1.1, is a prospective, two-center, short-term cross-sectional study to assess the reproducibility and repeatability of a set of specified ultrasound-based quantitative imaging biomarkers. The primary focus will be on imaging biomarkers of the liver fibrosis component of nonalcoholic fatty liver disease (NAFLD), rather than the steatosis or inflammation component. The rationale is that the fibrosis component is linked most closely to survival and other clinical outcomes. Study 1.1 will also collect data to explore vendor- or device-specific investigational biomarkers on other components of NAFLD such as steatosis and possibly inflammation.

Inclusion Criteria:

• Adult (age ≥ 18 years)
• Known or suspected NAFLD based on prior biopsy ≤ 36 months consistent with NAFLD OR
• Abnormal ALT (>30 U/L for men, > 19 U/L for women) without other common causes such as HCV, HBV, AND meets criteria within 36 months for ATP III criteria (2005 revision) for metabolic syndrome with any 3 of the 5:

Waist circumference (WC) > 102 cm (M) or > 88 cm (F)

• Fasting glucose ≥ 100 mg/dL or Rx
• TG≥150mg/dLorRx
• SBP > 130 mmHg
• DBP>85mmHg or Rx
• Able and willing to participate, including maintaining steady-state: physical activity, alcohol use, medications
• Classifiable into one of the following enrollment categories by FIB-4 (ALT, AST, platelets, date of birth) collected at screening visit if not available already within 3 months prior:

Low likelihood of advanced fibrosis: FIB-4 ≤ 1.3 (about one-third of enrolled participants, minimum 8, maximum 18), Intermediate likelihood of advanced fibrosis: 1.3 < FIB-4 < 2.67 (about one-third of enrolled participants, minimum 8, maximum 18), High likelihood of advanced fibrosis: FIB-4 ≥ 2.67: (about one-third of enrolled participants, minimum 8, maximum 18)

Exclusion Criteria:

• Liver disease other than NAFLD
• Excess alcohol consumption (≥ 2 units/day for women and ≥ 3 units/day for men)
• Current diagnosis of drug induced liver injury
• Receiving drug or placebo in treatment trial now or within 30 days
• Weight loss or gain of ≥ 5 kg in prior 3 months
• Other factors that in the judgment of the principal investigator might preclude study completion
• Women who state they are pregnant. Women who state they are pregnant will be excluded in an abundance of caution, since pregnancy might increase intra-abdominal pressure which in turn might affect the assessment of the different-day reproducibility coefficient of ultrasound and VCTE measurements. Women who state they might be pregnant will be required to do a urine pregnancy test to establish eligibility.
• Patients with active implants such as pacemakers or defibrillators or any other contraindication to ultrasound or VCTE scanning.