AMULET

Aim

To compare the diagnostic accuracy of an abbreviated liver MRI scan without contrast and liver Ultrasound scans for the diagnosis of early HCC in people with cirrhosis who are at high risk of developing HCC and are undergoing surveillance.

Background 

Alcohol excess, fatty liver, and hepatitis B or C can lead to liver cirrhosis. It is estimated that a third of people with cirrhosis will develop liver cancer in their lifetime. If liver cancer is diagnosed early it can be cured.

Ultrasound scans can raise suspicion for liver cancer and are usually done every 6 months (surveillance) in people with cirrhosis to help with early diagnosis. However, ultrasound can miss early cancers even in people having scans every 6 months. Furthermore, the risk of cancer is higher in people with more advanced cirrhosis and in people with cirrhosis from hepatitis B or C and it is possible that they need better tests than ultrasound.  

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 accumulation in the brain with repeated contrast injections. MRI scans without contrast are not toxic, could be done in 20 minutes and are cheaper, so can be done every 6 months.

In our experience, MRI without contrast may raise suspicion of liver cancer in cases missed by ultrasound, so it could be used for surveillance instead of ultrasound. In this study we want to find out if it is feasible to use a quick MRI without contrast as surveillance for liver cancer in people with cirrhosis in the NHS, and to compare this MRI with ultrasound.

Design and Methods

This will be a prospective, multicentre study in 300 participants with cirrhosis at high risk of developing HCC. Study participants will have an ultrasound scan every 6 months like all people with cirrhosis and an additional 6 monthly non-contrast MRI scan for 3 years (6 visits).

If the ultrasound or non-contrast MRI shows a possible cancer, an MRI scan with contrast will be done for definitive diagnosis. All participants will have an MRI with contrast at the end of 3 years to ensure that no cancers were missed. Participants will be asked to complete questionnaires to measure quality of life and anxiety, and data will be collected from their medical notes. If we find that quick non-contrast MRI is feasible for 6-monthly surveillance in the NHS and better than ultrasound for the detection of early liver cancer, we will develop a larger study to evaluate these tests in all people with liver cirrhosis and not just those at higher risk of liver cancer.  

 Main objectives:

• Determine feasibility of conducting an MRI study in people with cirrhosis in the NHS
• Evaluate the diagnostic performance of non-contrast enhanced MRI (nceMRI) and ultrasound scans (USS) as surveillance tools for HCC diagnosis

Secondary objectives include:

• Measures of quality of life and anxiety related to surveillance
• Mechanistic sub study to evaluate the liver parenchyma 

Patient and Public Involvement (PPI)

Four people with liver cirrhosis and liver cancer, one carer, and the Hepatitis C Trust reviewed the study. All supported the study and strongly felt that it will benefit people with cirrhosis. They identified anxiety from medical tests as an important patient concern so we added an anxiety questionnaire to measure this. A PPI advisory panel will be formed for the study.    

Recruitment

AMULET will recruit 300 patients with cirrhosis from more than 30 hospital sites around the UK.

Current recruitment total: 14

Map of recruiting sites and sites in active set up