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A Prospective Intra-individual Cohort Study to Compare Gadoxetic Acid (Primovist®)-Enhanced Magnetic Resonance Image and Ultrasonography for the Surveillance of Early Stage Hepatocellular Carcinoma in Patients at High-risk

20 Years
Open (Enrolling)
Cirrhosis of Liver

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Trial Information

A Prospective Intra-individual Cohort Study to Compare Gadoxetic Acid (Primovist®)-Enhanced Magnetic Resonance Image and Ultrasonography for the Surveillance of Early Stage Hepatocellular Carcinoma in Patients at High-risk

Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer-related deaths
worldwide. Cirrhosis, particularly when related to viral hepatitis, is the most notable risk
factor for HCC and is found in nearly 80-90% of cases.

The stage of disease at the time of diagnosis largely determines the effectiveness of
treatment. The treatment of advanced HCC continues to be primarily palliative, with curative
options only available for early HCC. Unfortunately, less than 30% of patients are
diagnosed early enough to meet criteria for resection, transplantation, or local ablation.

Surveillance strives to detect HCC at an early stage when it is amenable to curative therapy
to reduce mortality. Current practice guidelines recommend surveillance of cirrhotic
patients with ultrasonography (USG) every 6 months. However, USG has been reported to have a
sensitivity of between 65% and 80% when used as a screening test. However, with the
advancement of cirrhosis, the sensitivity of USG decreases, while the risk for HCC

Gadoxetic acid (Primovist®)-enhanced magnetic resonance imaging (MRI) of the liver has been
demonstrated to be of clinical value for local staging before HCC surgery and for the
assessment of patients with inconclusive conventional imaging findings. The detection
sensitivity of Primovist-MRI has been known to be as high as 90-95%, which is significantly
higher than USG or multiphase computer tomography (CT) scan. MRI does not have radiation
exposure, which is a meaningful merit to be used as a surveillance test. However, MRI has
never been considered for surveillance or screening of HCC.

Thus, the hypothesis to be proved by this study is as follows; Primovist-MRI should show
significantly higher sensitivity compared to USG for the detection of early stage HCC when
both of these imaging modalities are used with the interval of 6 months in patients with
cirrhosis at high risk of developing HCC. The investigators will also analyze whether the
specificity of Primovist-MRI are not compromised by its high sensitivity.

Inclusion Criteria:

Patients with liver cirrhosis with the 1 year risk of HCC of 5% or higher meeting all of
following criteria;

1. The evidence of cirrhosis of any etiology within 12 months prior to screening
Definition of cirrhosis by any of following methods

- 1) Histologically by liver biopsy;

- 2) Non-histologically by evidence of portal hypertension in the presence of
chronic liver disease;

- Evidence of portal hypertension, including any of followings;

1. The identification of splenomegaly on USG, CT, or MRI examinations
with typical features of cirrhosis

2. The identification of esophageal or gastric varices on endoscopic

2. High Risk Index (>=2.33); Risk Index = 1.65 (if the prothrombin activity is <=75%) +
1.41 (if the age is 50 years or older) + 0.92 (if the platelet count is
<=100x10(3)/mm3) + 0.74 (if the presence of anti-hepatitis C virus [HCV] or hepatitis
B surface antigen [HBsAg] is positive).

3. Older than 20 years of age

4. Absence of previous or current history of HCC

5. Absence of HCC should be identified by liver USG, dynamic CT, or contrast-enhanced
MRI within 6 months prior to screening

6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2

7. Patient is able to comply with scheduled visits, evaluation plans, and other study

8. Patient is willing to provide written informed consent

Exclusion Criteria:

Presence of any of following criteria;

1. Active or suspected cancer other than HCC, or a history of malignancy where the risk
of recurrence is >20% within 2 years

2. Significant medical comorbidities in which survival is predicted to be less than 3

3. Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73m2

4. Precautions for MRI (cardiac pacemaker, ferromagnetic implants, etc.)

5. Severe claustrophobia that may interfere with protocol compliance.

6. Any other condition which, in the opinion of the Investigator, would make the patient
unsuitable for enrollment or could interfere with the completing the study.

Type of Study:


Study Design:

Observational Model: Cohort, Time Perspective: Prospective

Outcome Measure:

The detection sensitivity of early stage HCC

Outcome Description:

The number of definite HCC nodules of early stage detected by a given modality divided by the total number of definite HCC nodules of early stage detected by any of 2 modalities plus interval cancers Early stage (stage A or 0) HCC is defined by the Barcelona Clinic Liver Cancer staging system (BCLC): A single HCC <5 cm or <=3 lesions each <3 cm in diameter, without gross vascular invasion or extrahepatic metastasis.

Outcome Time Frame:

during the 1.5-year study period (from the date of first screening to 6 months following the last screening)

Safety Issue:


Principal Investigator

Young-Suk Lim, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Asan Medical Center


South Korea: Institutional Review Board

Study ID:




Start Date:

November 2011

Completion Date:

December 2014

Related Keywords:

  • Cirrhosis of Liver
  • hepatocellular carcinoma
  • surveillance
  • gadoxetic acid
  • MRI
  • Carcinoma
  • Liver Cirrhosis
  • Fibrosis
  • Carcinoma, Hepatocellular