LITMUS Imaging Study

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: NAFLD; Fibrosis, Liver; NASH - Nonalcoholic Steatohepatitis; NASH; Steatosis of Liver

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).

• Study Type: Observational
• Enrollment (Estimated): 450

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Helsinki University Hospital
• France
  • Angers, France
    • Le Centre de Recherche Clinique (CRC) du CHU d'Angers
  • Paris, France
    • Institut ICAN - Institute of Cardiometabolism And Nutrition Hôpital de la Pitié Salpêtrière
• Germany
  • Mainz, Germany
    • Universitatsmedizin der Johannes Gutenberg Universitat Mainz
  • Würzburg, Germany
    • Universitätsklinikums Würzburg
• Greece
  • Athens, Greece, 11527
    • Laiko General Hospital of Athens
• Italy
  • Palermo, Italy
    • Università di Palermo
  • Torino, Italy
    • Department of Medical Sciences University of Torino
• Spain
  • Barcelona, Spain
    • Vall d'Hebron University Hospital
  • Sevilla, Spain
    • Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocío University Hospital
  • Valladolid, Spain
    • HU Clínico de Valladolid
• Sweden
  • Linköping, Sweden
    • Linkoping University Hospital
• Switzerland
  • Bern, Switzerland
    • Inselspital, University Hospital
• United Kingdom
  • Cambridge, United Kingdom
    • Addenbrookes Hospital
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Nottingham, United Kingdom
    • Queens Medical Centre
  • Oxford, United Kingdom, OX3 9DU
    • Oxford University Hospitals NHS Foundation Trust
• United States
  • Texas
    • San Antonio, Texas, United States, 78201
      • Pinnacle Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with known or suspected NAFLD who are undergoing liver biopsy as part of their routine clinical care and are already participating in the European NAFLD Registry

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
LITMUS Imaging Study Group; Patients within the European NAFLD Registry who have also consented to participate in the LITMUS Imaging study

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Assistance Publique - Hôpitaux de Paris; University of Nottingham; Novartis; Pfizer; University of Palermo; Takeda; Boehringer Ingelheim; Linkoeping University; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Newcastle University; University of Bern; University of Helsinki; University of Turin, Italy; University of Cambridge; Intercept Pharmaceuticals; University of Seville; Perspectum; Antaros Medical; University Medical Center Mainz; ICAN Nutrition Education and Research; University of Angers; Pinnacle Clinical Research, PLLC; Resoundant Inc
• Investigators: Principal Investigator: Michael Pavlides, MBBS, DPhil, University of Oxford

Publications and helpful links

General Publications

• Pavlides M, Mozes FE, Akhtar S, Wonders K, Cobbold J, Tunnicliffe EM, Allison M, Godfrey EM, Aithal GP, Francis S, Romero-Gomez M, Castell J, Fernandez-Lizaranzu I, Aller R, Gonzalez RS, Agustin S, Pericas JM, Boursier J, Aube C, Ratziu V, Wagner M, Petta S, Antonucci M, Bugianesi E, Faletti R, Miele L, Geier A, Schattenberg JM, Tilman E, Ekstedt M, Lundberg P, Berzigotti A, Huber AT, Papatheodoridis G, Yki-Jarvinen H, Porthan K, Schneider MJ, Hockings P, Shumbayawonda E, Banerjee R, Pepin K, Kalutkiewicz M, Ehman RL, Trylesinksi A, Coxson HO; LITMUS Consortium Investigators; Martic M, Yunis C, Tuthill T, Bossuyt PM, Anstee QM, Neubauer S, Harrison S. Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol. Contemp Clin Trials. 2023 Nov;134:107352. doi: 10.1016/j.cct.2023.107352. Epub 2023 Oct 4.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2019
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: April 11, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: MRI; MRE; liver stiffness; diagnostic study; diffusion weighted imaging; Liver MultisScan; Magnetic Resonance Elastography; Magnetiic Resonance Imaging; deMILI; proton density fat fraction; PDFF; iron corrected T1; cT1; LITMUS
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fibrosis; Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis
• Other Study ID Numbers: IRAS ID 250344; 18/LO/1953 (Other Identifier: NHS Health Research Authority)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No