Fibrosis, Liver, NAFLD, NASH, NASH - Nonalcoholic Steatohepatitis, Steatosis of Liver
Conditions
Keywords
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
Brief summary
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
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).
Interventions
None listed
Sponsors
Newcastle University
University of Nottingham
University of Cambridge
University of Seville
Pinnacle Clinical Research, PLLC
ICAN Nutrition Education and Research
Assistance Publique - Hôpitaux de Paris
University of Angers
University of Palermo
University of Turin, Italy
University Medical Center Mainz
University of Helsinki
University of Bern
Linkoeping University
Perspectum
Antaros Medical
Resoundant Inc
Pfizer
Novartis
Takeda
Intercept Pharmaceuticals
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Boehringer Ingelheim
University of Oxford
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Recruited to the European NAFLD Registry 2. 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. 3. Participant is willing and able to give informed consent for participation in the study.
Exclusion criteria
1. 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. 2. 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) 3. 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic accuracy of imaging biomarkers for severity of liver fibrosis on histology as reference standard | baseline | sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic accuracy of imaging biomarkers for diagnosis of NASH on histology as reference standard | baseline | sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve |
| Diagnostic accuracy of imaging biomarkers for histologically assessed fat and iron deposition as reference standard | baseline | sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve |
| To study the natural history of NAFLD and how this may impact prognosis | evaluation of biomarkers at baseline and after 2 years | 1. Longitudinal correlation of change (δ) in MR and US elastography biomarker values with clinical phenotype data\* 2. Survival analysis for the change (δ) in biomarker values |
| To evaluate reproducibility and observer dependent variability in reporting of liver imaging biomarkers | evaluation of biomarkers within 30 days | Statistical correlation of MR and US elastography data obtained from the same patients acquired or analysed on two time points |
| To identify physiological factors that confound the performance of imaging biomarkers for the assessment of fibrosis | baseline | 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) |
Countries
Finland, France, Germany, Greece, Italy, Spain, Sweden, Switzerland, United Kingdom, United States
Outcome results
None listed