Abbreviated Magnetic Resonance Imaging vs Ultrasound Surveillance for Liver Cancer dETection in People at High Risk of Developing Liver Cancer (AMULET)

Aim: To use magnetic resonance imaging (MRI) scans without contrast to help improve diagnosis of liver cancer in people who are at increased risk of developing liver cancer.

Background: People with any condition that affects the liver over a long period of time can develop cirrhosis. Conditions and risk factors that can lead to cirrhosis include alcohol excess, liver steatosis (lipid or fat accumulation in the liver) and infection with the viruses hepatitis B and C. One of the concerns about people with cirrhosis is that they are at increased risk of developing liver cancer. People with cirrhosis are recommended to have an ultrasound scan (USS) every 6 months (surveillance for liver cancer) so that if a cancer develops, it is diagnosed at an early stage when it can be cured. However, ultrasound can miss cancers even in people having scans every 6 months. Furthermore, the risk of cancer is not alike among people with cirrhosis. For example, people with more advanced cirrhosis and those with cirrhosis from hepatitis B are at higher risk. It is therefore possible that better tests than ultrasound are needed for people with cirrhosis who are at particularly high risk of developing cancer.

Computed tomography (CT) and Magnetic Resonance Imaging (MRI) scans with dye injection (contrast) are used for liver cancer diagnosis. However, they cannot be done every 6 months because of costs, capacity and toxicity from high CT radiation doses, and MRI contrast build-up in the brain with repeated MRI contrast injections. MRI scans without contrast are not toxic, could be done in 20 minutes and are cheaper, so could be done every 6 months. In the experience of the study investigators, MRI without contrast may raise suspicion of liver cancer in cases missed by ultrasound, so it could be used for surveillance instead of ultrasound. This study aims to find out if it is feasible to use a quick MRI (20 minutes) without contrast as surveillance for liver cancer in people at high risk of liver cancer due to liver cirrhosis and to compare this MRI with ultrasound.

Design and Methods: The investigators will recruit 300 people at higher risk of developing liver cancer because of cirrhosis. Study participants will have an ultrasound scan every 6 months as they would in their standard clinical care and an additional 6 monthly non-contrast MRI scan for 30 months (6 visits). If the ultrasound or non-contrast MRI raises concern for a possible liver cancer, an MRI scan with contrast (with dye injection) will be done for definitive diagnosis. All participants will have an MRI with contrast at the end of 30 months (M30) to ensure that no cancers were missed. Participants will be asked to complete questionnaires to measure quality of life, anxiety, and their experience of MRI and ultrasound scans and data will be collected from their medical notes. The number of liver cancers detected by ultrasound will be compared to the number detected by the non-contrast MRI scans.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; Cirrhosis; Cirrhosis of the Liver; Cirrhosis and Chronic Liver Disease; Cirrhosis Due to Hepatitis B; Cirrhosis Due to Hepatitis C
• Intervention / Treatment: Diagnostic test: non contrast enhanced MRI

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Michael Pavlides, DPhil; Phone Number: +44 1865234577; Email: michael.pavlides@cardiov.ox.ac.uk

Study Locations

• United Kingdom
  • Bournemouth, United Kingdom
    • Recruiting
    • Bournemouth University Hospital
  • Oxon
    • Oxford, Oxon, United Kingdom, ox3 9du
      • Recruiting
      • Oxford University Hospitals NHS Foundation Trudt
      • Contact: Michael Pavlides, DPhil; Email: michael.pavlides@ouh.nhs.uk
      • Principal Investigator: Michael Pavides, DPhil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Participants with a high risk of HCC will be included. Participants will have liver cirrhosis from Alcohol related liver disease, metabolic dysfunction associated steatotic liver disease, chronic hepatitis C, chronic hepatitis B or genetic haemochromatosis, or with chronic liver disease and prior successful treatment for HCC without recurrence and who are back in surveillance with USS.

Description

Inclusion Criteria:

• • Participant is willing and able to give informed consent for participation in the study AND

  • All genders, aged 18 years or above AND
  • Eligible for HCC US surveillance in the opinion of the local investigators AND
  • Child Pugh score A or B AND
  • Diagnosed with liver cirrhosis due to ArLD, MASLD, chronic hepatitis C, chronic hepatitis B, genetic haemochromatosis AND
  • Have an annual risk of HCC of at least 3% as determined by the aMAP score OR
  • Participants with chronic liver disease (with or without cirrhosis) who had successful treatment for HCC, have not had a recurrence and have returned to 6 monthly surveillance with USS

Exclusion Criteria:

• • Contraindication to MRI

  • Known allergy / reaction to intravenous gadolinium contrast
  • Prisoners
  • Pregnancy or breast feeding
  • Previous liver transplant
  • Participants who are known to have indeterminate liver nodules on prior imaging requiring ongoing follow-up with MRI or CT
  • Previous HCC treated with curative intent and still being followed up with CT or MRI with contrast for possible recurrence
  • Estimated glomerular filtration rate of <30 ml/min/1.73m2
  • Participant is on haemodialysis
  • Participants who are unlikely to comply with the study procedures in the opinion of the local investigator
  • In the view of the clinician, if the participant has a co-morbidity likely to lead to death within the following 12 months

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
non contrast MRI AND standard of care USS; Participants undergo ultrasound every 6 months as per routine clinical care. In addition they undergo research non-contrast enhanced MRI at the same 6 monthly intervals	Diagnostic test: non contrast enhanced MRI; 6 monthly non contrast enhance MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance for HCC	True positive tests for HCC per round of surveillance False positive tests for HCC per round of surveillance Positive predictive value for HCC per round of surveillance True negative tests for HCC over the 30 months of surveillance False negative tests for HCC over the 30 months of surveillance Sensitivity and specificity of nceMRI and USS for HCC over 30 months of surveillance	from enrolment to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
stage and size of HCC at diagnosis	Numbers of HCC detected by nceMRI and USS at a very early, early, intermediate or advanced stage as defined by the Barcelona Clinic Liver Cancer staging system. The number and size of HCC tumours per participant with HCC The number of new indeterminate lesions identified at each surveillance round	from enrolment to 30 months
proportion of participants that receive treatment with curative intent	Proportion of participants diagnosed with HCC who go on to receive treatment with curative intent	from enrolment to 30 months
Quality of Life, Anxiety and Depression	Results of the EQ-5D-5L questionnaire and Hospital Anxiety and Depression Scale questionnaire	from enrolment to 30 months
participant experience	Results of participant experience questionnaire	baseline, and month 24
multivariate models	Sensitivity and specificity of multivariable models for the diagnosis of HCC	month 30
mechanistic sub-study quantitative MRI metrics	Quantitative variables extracted from MRI data; T1 (ms), R2* (ms), PDFF (%), ADC (mm2/s)	from baseline to months 30
long term outcomes	A composite end point including the outcomes of: all cause mortality, liver related mortality, liver decompensation (ascites, hepatic encephalopathy, variceal bleeding), hepatocellular cancer, non primary liver cancer, liver transplantation.	Up to 10 years after the last study MRI scan is performed
number of unused appointments	We will count how many appointments for HCC surveillance are unused due to appointments that are missed by participants or cancelled buy the health care provider, or due to participants being lost to follow-up or participants where HCC surveillance is no longer indicated.	from enrolment to 30 months

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: University of Nottingham; Nottingham University Hospitals NHS Trust; Glasgow Caledonian University; Bournemouth University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2039

Study Registration Dates

• First Submitted: October 16, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 26, 2024

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: abbreviated MRI; SURVEILANCE; DIAGNOSTIC ACCURACY; no contrast enhanced MRI
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Pathological Conditions, Signs and Symptoms; Carcinoma, Hepatocellular; Fibrosis
• Other Study ID Numbers: IRAS ID 333813; 24/NW/0286 (Other Identifier: REC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymised data may be shared with global academic, commercial or other collaborators after analysis and publication of results, which is expected to be after the end of the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No