Contrast-Enhanced Ultrasound Imaging in Diagnosing Liver Cancer in Patients With Cirrhosis

PRIMARY OBJECTIVES:

I. To evaluate the sensitivity, specificity, positive and negative predictive values of
contrast-enhanced ultrasound (CEUS) for diagnosis of hepatocellular carcinoma (HCC) in
patients at risk for HCC in a multicenter setting.

SECONDARY OBJECTIVES:

I. To validate CEUS Liver Imaging Reporting and Data System (LI-RADS) and determine the
prevalence of HCC in each CEUS LI-RADS category.

II. To evaluate inter-reader reliability of CEUS for HCC diagnosis. III. To evaluate
covariates that might limit diagnostic performance of CEUS for HCC diagnosis.

Inclusion Criteria:

- Capable of making informed decisions regarding his/her treatment

- Have known cirrhosis or other risk factors for HCC, based on American Association for
the Study of Liver Diseases (AASLD) and European Association for the Study of the
Liver (EASL) guidelines (applicable in each site jurisdictions)

- Patients with untreated focal liver observations on liver ultrasound or multiphase
contrast-enhanced CT or MRI performed as part of clinical standard of care within 4
weeks before patient enrollment.

OR

• Patients with untreated focal liver observations scheduled for follow-up multiphase
contrast-enhanced CT or MRI, biopsy or surgical excision as part of clinical standard of
care. CEUS should be performed within 4 weeks before or after follow-up imaging or within 4
weeks before biopsy or surgical excision.

Exclusion Criteria:

- Patients who are pregnant or lactating

- Patients with focal liver observations less than 5 mm or greater than 5 cm in size

- Patients with contraindications to CEUS

- Patients with contraindications to both CT and MRI

- Patients who are medically unstable, terminally ill, or whose clinical course is
unpredictable

- Liver nodule previously treated with trans-arterial or thermal ablation

- Patients who have received an investigational drug in the 30 days before CEUS, or will
receive one within 72 hour after their CEUS exam