Gadoxetic Acid-MRI Versus Ultrasonography for the Surveillance of Hepatocellular Carcinoma in High-risk Patients
Gadoxetic Acid-MRI Versus Ultrasonography for the Surveillance of Hepatocellular Carcinoma in High-risk Patients
Current practice guidelines recommend surveillance for hepatocellular carcinoma (HCC) in
 liver cirrhosis patients with ultrasonography (USG) every 6 months. However, with the
 advancement of cirrhosis, the sensitivity of USG decreases, while the risk for HCC increases.
 Gadoxetic acid (Primovist®)-enhanced magnetic resonance imaging (MRI) has been demonstrated
 to be of clinical value for diagnosis of HCC with the detection sensitivity of 90-95%, which
 is significantly higher than USG. 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.
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 increases.

 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
 examination

 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
 procedures.

 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. Child-Pugh score >9

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

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

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

 6. Severe claustrophobia that may interfere with protocol compliance.

 7. 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.