LITMUS Imaging Study

Study Overview
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Brief Summary
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The LITMUS Imaging Study is a prospectively recruited, observational study of patients with histologically characterised non-alcoholic fatty liver disease (NAFLD). It aims to evaluate the diagnostic performance of imaging biomarkers (ultrasound elastography and magnetic resonance biomarkers) against NAFLD histological scores in a cross-sectional analysis and the natural history of NAFLD in a longitudinal study.

Detailed Description
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The LITMUS Imaging study is a non-interventional, observational study conducted in parallel to the European NAFLD Registry (NCT04442334), collecting cross-sectional and longitudinal ultrasound elastography and magnetic resonance elastography and imaging data. The LITMUS Imaging study recruits patients with NAFLD who are having a clinically indicated liver biopsy and are already participating in the European NAFLD Registry. Patients in the LITMUS Imaging study have additional imaging assessments at baseline (within 100 days of baseline liver biopsy) and 2 years after baseline (no follow-up biopsy necessary). Imaging assessments include point shear wave elastography, 2D shear wave elastography, MRI scans (Liver Multiscan, deMILI, diffusion weighted imaging, proton density fat fraction, T1 mapping) and MR elastography. Link-anonymised magnetic resonance data are uploaded to a central online portal and analysed centrally by 4 imaging core labs provided by Perspectum (Liver Multiscan), Antaros Medical (MR elastography and DWI), Resoundant (vendor specific PDFF) and University of Seville (deMILI).

Official Title
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Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & Validation of Imaging Modality Performance Across the NAFLD Spectrum in a Prospectively Recruited Cohort

Conditions
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NAFLD, NASH, NASH - Nonalcoholic Steatohepatitis, Fibrosis, Liver, Steatosis of Liver

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recruited to the European NAFLD Registry Patient had a liver biopsy less than 3 months prior to enrolment into the study or is having a liver biopsy in less than 3 months' time for the assessment of NAFLD. Participant is willing and able to give informed consent for participation in the study. Exclusion Criteria: Patients that do not speak the language in which the patient information is written will be excluded. Due to the nature of the study, being able to read the information about the study or access to a relevant interpreter is a necessary criterion for participant's safety in regards to MR scanning. Patients judged by the investigator to be unsuitable for inclusion in the study (e.g. where the investigator feels that the participant will not be able to comply with the study procedures) Any contra-indication to Magnetic Resonance Imaging (MRI) (e.g. ferrous metal implants/fragments, implantable cardiac defibrillator or permanent pacemaker, metal clips following neurosurgery, pregnancy, other condition that would make MR scanning unsafe in the opinion of the scanner operator)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| LITMUS Imaging Study Group<br>Patients within the European NAFLD Registry who have also consented to participate in the LITMUS Imaging study | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy of imaging biomarkers for severity of liver fibrosis on histology as reference standard | sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy of imaging biomarkers for diagnosis of NASH on histology as reference standard | sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve | baseline | 
| Diagnostic accuracy of imaging biomarkers for histologically assessed fat and iron deposition as reference standard | sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve | baseline | 
| To study the natural history of NAFLD and how this may impact prognosis | Longitudinal correlation of change (δ) in MR and US elastography biomarker values with clinical phenotype data* Survival analysis for the change (δ) in biomarker values | evaluation of biomarkers at baseline and after 2 years | 
| To evaluate reproducibility and observer dependent variability in reporting of liver imaging biomarkers | Statistical correlation of MR and US elastography data obtained from the same patients acquired or analysed on two time points | evaluation of biomarkers within 30 days | 
| To identify physiological factors that confound the performance of imaging biomarkers for the assessment of fibrosis | Statistical correlation of MR scans and US elastography imaging biomarkers with liver histology parameters (steatosis, iron deposition, inflammation) and other clinical data (demographics, lab results, patient characteristics) | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver MultisScan, Magnetic Resonance Elastography, Magnetiic Resonance Imaging, deMILI, diffusion weighted imaging, proton density fat fraction, PDFF, iron corrected T1, cT1, liver stiffness, MRI, MRE, diagnostic study, LITMUS