Usefulness of Non-contrast MagnetIc Resonance imAging Versus Non-Contrast Ultrasonography for surveiLlancE of HepatoCellular Carcinoma [MIRACLE-HCC]

Study Overview
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Brief Summary
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The investigators will investigate the usefulness of ultrasonography versus non-contrast magnetic resonance imaging for surveillance of hepatocellular carcinoma through this prospective, randomized trial.

Detailed Description
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Hepatocellular carcinoma (HCC) is one of the major complications in patients with chronic liver disease. The prognosis of HCC relies on the extent of disease at the time of diagnosis. Hence to detect cancer at an earlier stage, a regular surveillance test is important for the subjects with a high risk of developing cancer. Current guidelines recommend a regular surveillance using ultrasonography at a 6 month-interval. Ultrasonography is a non-invasive and safe procedure, yet it is limited by the skills of the operator and it is often difficult to differentiate cancer from regenerating nodules especially in atrophied cirrhotic liver. According to a recent meta-analysis, the overall sensitivity and specificity of detecting liver cancer using ultrasonography were both over 90%, however the sensitivity was decreased to 60% in detecting early lesions in which surgery or liver transplantation is indicated. Of note, addition of AFP to ultrasonography also failed to increase the sensitivity in detecting small cancers. Taken together, there is a need to develop a new surveillance test with an improved sensitivity and specificity. Recently, a retrospective study reported that CT or MRI showed a better sensitivity than ultrasonography in detecting early liver cancer. However, performing CT as a surveillance test is limited by frequent exposure to radiation and contrast-dye agent. Although MRI does not have the risk of radiation-exposure, it is limited by the high cost. On the contrast, non-contrast MRI offers a cost that is comparable to US and an absence of exposure to radiation or contrast-dye agent, which suggests non-contrast MRI as a good alternative surveillance tool for early detection of HCC. Therefore, in this prospective, randomized trial, the investigators will investigate the usefulness of ultrasonography versus non-contrast magnetic resonance imaging for surveillance of hepatocellular carcinoma.

Official Title
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Usefulness of Non-contrast MagnetIc Resonance imAging Versus Non-Contrast Ultrasonography for surveiLlancE of HepatoCellular Carcinoma [MIRACLE-HCC]

Conditions
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Compensated Liver Cirrhosis

Intervention / Treatment
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* Radiation: Ultrasonography
* Radiation: non-contrast MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject between 20 and 70 years of age at the time of randomization Has chronic liver disease with compensated liver cirrhosis (Child-Pugh score A), defined as 1) histologically confirmed cirrhosis, or 2) has chronic liver disease and shows the presence of splenomegaly or other typical findings of liver cirrhosis on ultrasonography, computed tomography, or magnetic resonance imaging, or 3) has chronic liver disease and shows the presence of endoscopically-confirmed esophageal or gastric varices Absence of severe cardiovascular, pulmonary, renal or infectious diseases, other than chronic liver disease Absence of a history of malignancy within previous 5 years Can and will comply with the requirements of the protocol (e.g. return for follow-up visits), in the opinion of the investigator Has provided written informed consent Exclusion Criteria: Greater than 70 years of age Presence of liver cancer or other intrahepatic malignancy Has a history of malignancy within previous 5 years Is pregnant or breast-feeding

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ultrasonography<br>Subjects will be regularly screened for HCC by ultrasonography with serum AFP(alpha fetoprotein). | Radiation: Ultrasonography<br>* Subjects will be randomly allocated to either Ultrasonography arm or Non-contrast MRI arm for their surveillance method.<br>|
| Experimental: Non-contrast MRI<br>Subjects will be regularly screened for HCC by non-contrast magnetic resonance imaging(MRI) with serum AFP(alpha fetoprotein). | Radiation: non-contrast MRI<br>* Subjects will be randomly allocated to either Ultrasonography arm or Non-contrast MRI arm for their surveillance method.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor stage of HCC | Comparing tumor stage and resectability rate of HCC between participants undergoing HCC surveillance using ultrasonography and non-contrast MRI. | 6 months | 
| Resectability rate of HCC | Comparing tumor stage and resectability rate of HCC between participants undergoing HCC surveillance using ultrasonography and non-contrast MRI. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Five-year overall survival |  | 5 years after the study enrollment | 
| Liver-related mortality |  | 5 years after the study enrollment | 
| Post-treatment recurrence rate |  | 5 years after the study enrollment |