Clinical Trial Multi-analyte Blood Test

This multi-site, prospective study is designed to compare the sensitivity and specificity

of a multi-analyte blood test alone to ultrasound alone for the detection of HCC within a

population at high risk of HCC due to liver cirrhosis. Subjects will be enrolled until

the pre-determined number of subjects are enrolled.

Subjects at high risk for developing HCC due to liver cirrhosis and who are eligible for

liver cancer surveillance as determined by the patient's physician and who meet all

inclusion and exclusion eligibility criteria as described in this protocol, will be

invited to participate in this study. Subjects will then read, understand and sign the

Informed Consent Form and the HIPAA Authorization Agreement for Medical Records Form.

For each subject upon enrollment, the following blood analytes will also be determined:

creatinine, prothrombin time, bilirubin, blood platelet count, ALT, AST and ALP. The

results of all clinical laboratory tests will be recorded by use of the subject's Case

Report Form. Whole blood samples drawn for the multi-analyte blood test will be collected

(according to the instructions provided with each sample collection kit) by using the

multi-analyte Sample Collection, Stabilization and Shipping Kit, and shipped to a central

LAM laboratory for testing. Samples will be assayed by laboratory technicians blinded to

the results of any other testing. Within the same clinical visit as the blood draws (when

possible), subjects will undergo conventional ultrasound to examine the liver. Every

subject will then go on to diagnostic imaging by multiphasic MRI. The results of

diagnostic imaging will primarily be scored by LI-RADS score and the number and size of

any malignant lesions identified will be recorded. The images of all MRI, CT, or

ultrasound will be saved and uploaded for evaluation by a blinded, centralized team of

radiologists to confirm diagnosis. Any biopsy results or surgical pathology results that

are generated for study subjects as part of current clinical practice will also be

recorded.

Study procedures will consist of conventional ultrasound to examine the liver, providing

blood samples for testing with the multi-analyte blood test and other conventional blood

analytes, and diagnostic imaging by multiphasic MRI.

Upon enrolling in the study, subjects will commence the Initial Surveillance Visit (t=0

months). During the Initial Surveillance Visit, all enrolled subjects will undergo

ultrasound to examine the liver and provide blood samples for the multi-analyte blood

test and for determining conventional blood analytes. Every subject will then go on to

diagnostic imaging by multiphasic MRI. The results of diagnostic imaging will primarily

be scored by a Liver Reporting and Data System (LI-RADS) score. The data of all

diagnostic imaging by MRI will be saved and uploaded for evaluation by a blinded,

centralized team of radiologists, which will be used as the basis of the clinical truth

for all subjects.

After the Initial Surveillance Visit (t=0 months), subjects with an indeterminant HCC

finding by MRI (LI-RADS 3) will be recommended to up to three Follow-Up Visits (t=6

months, t=12 months, and t=18 months) to attempt to resolve the clinical truth for these

subjects. Each Follow-Up Visit will consist of an ultrasound to examine the liver,

providing blood samples for the multi-analyte blood test , as well as diagnostic imaging

by multiphasic MRI.

Although not required by this clinical protocol, any biopsy or surgical pathology

results, or any additional imaging (such as multiphasic CT) that are generated for study

subjects as part of current clinical practice will also be recorded for each subject and

the results shall be made available to the Sponsor if performed within 6 months of a

scheduled Visit. Biopsy and surgical pathology results that indicate a malignancy will be

used in place of diagnostic imaging as the clinical truth for each subject if performed

within 6 months of a scheduled visit and prior to database lock.

All study-related procedures will occur during the Study Duration Period, which consists

of the Initial Surveillance Visit for all subjects and up to three Follow-Up Visits for

subjects with an initial indeterminant HCC finding (LI-RADS 3) by diagnostic imaging.

After this Study Duration Period, no study related blood draws, imaging or procedures

will occur for these subjects.