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Patients with known liver cirrhosis and planned to undergo liver transplantation within 1 month will be eligible population in the study

Jae Ho Byun, MD, PhD

A prospective intra-individual study to investigate the diagnostic performance of gadoxetic acid-enhanced MR for the patients with liver cirrhosis using thin-section whole-explant as standard of reference

Liver cirrhosis is a progressive, diffuse disease of the liver characterized by hepatocyte necrosis, fibrosis, distortion of the normal hepatic architecture and a spectrum of nodular lesions that includes regenerative nodules (RN), dysplastic nodules (DN) and hepatocellular carcinomas (HCC). Since HCC is the leading cause of death among the patients with liver cirrhosis, Early and accurate diagnosis of HCC and its precursors by using optimal imaging technique is critical for its treatment and management.

Recently state-of-the-art magnetic resonance (MR) imaging with gadoxetic acid, which works both an extracellular and hepatocyte-specific contrast agent, has been increasing used to evaluate the patients with liver cirrhosis. Several studies correlated gadoxetic acid-enhanced MR of HCC and hepatocellular nodules with the pathology from biopsy or surgical resection specimens. However, all of those studies are limited by its lack of complete correlation between pathologic and imaging findings and the resulting bias being toward the positive studies. Ideally, the use of whole explant pathologic correlation would be helpful for exact characterization of HCC and its precursors on gadoxetic acid-enhanced MR.

The question of our study is how accurate gadoxetic acid-enhanced MR is in the evaluation of the patients with cirrhotic liver to detect HCC and dysplastic nodules and, by using thin-section whole-explant correlation following liver transplantation as the reference standard.

Gadoxetic Acid-enhanced MR Evaluation of Hepatocellular Carcinoma and Dysplastic Nodules in the Cirrhotic Liver

Gadoxetic Acid-enhanced MR Evaluation of Hepatocellular Carcinoma and Dysplastic Nodules in the Cirrhotic Liver: Prospective Pathologic Correlation With Explanted Liver

To assess the diagnostic sensitivity and specificity of gadoxetic acid-enhanced MR imaging to detect dysplastic nodules in the cirrhotic liver, using thin-section whole-explant as standard of reference

To characterize borderline hepatocelluar nodules (i.e.,1-3cm sized nodules without arterial hypervascularity) in the cirrhotic liver detected on hepatobiliary phase of gadoxetic acid-enhanced MR

Bayer

Jae Ho Byun

Associate Professor

Coagulants

Thrombin

Patients with liver cirrhosis with the 1-year risk of HCC of 5% or higher

; 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).

Young-Suk Lim, MD, PhD

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.

Gadoxetic Acid-MRI Versus Ultrasonography for the Surveillance of Hepatocellular Carcinoma in High-risk Patients

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

- The number of patients with definite HCC detected by a given modality divided by the total number of patients with definite HCC detected by any of 2 modalities plus interval cancers

* The number of patients with early stage HCC detected by a given modality divided by the total number of patients with early stage HCC 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.

* The number of patients with HCC nodules of very early stage detected by a given modality divided by the total number of definite HCC nodules of very early stage detected by any of 2 modalities plus interval cancers.
* Very early stage (stage 0) HCC is defined by the Barcelona Clinic Liver Cancer staging system (BCLC): A single HCC \<2 cm without gross vascular invasion or extrahepatic metastasis.

The false-positive rate was defined as the number of tests with positive findings by a specific imaging modality in patients without a HCC.

The positive predictive value was the number of true positive test results in patients with the positive tests in a specific modality.

Asan Medical Center

Professor

The patients were evaluated by three rounds of screening tests with paired US and gadoxetic acid-enhanced MRI at 6-month intervals

US+MRI

The patients were evaluated by three rounds of screening tests with paired US and gadoxetic acid-enhanced MRI at 6-month intervals.

Age, Continuous

Sex: Female, Male

Korean

Race/Ethnicity, Customized

South Korea

Region of Enrollment

Professor Young-Suk Lim

The HCC detection rate was defined as the number of patients with HCC detected by a given modality divided by the total number of patients with HCC detected by all modalities and by follow-up dynamic CT scan. The HCC detection rates from ultrasonography and MRI were compared.

Ultasonography

Gadoxetic Acid-enhanced MRI

Detection Rate of Patients With HCC

Detection Rate of Patients With Early Stage HCC

Of the 43 patients, 32 (74.4%) had very early-stage.

Detection Rate of Patients With Very Early Stage HCC

False Positive Rate

Positive Predictive Value for HCC

Overall Study

This group meets eligibility criteria, and undergo contrast-enhanced ultrasound (CEUS) and scheduled gadoxetic acid MRI (gadoxetic acid-enhanced liver MRI; EOB-MRI; Gd-EOB-MRI)

CEUS is performed using SonoVue (Bracco, Milan, Italy) intravenous administration in eligible participants within a month before/after EOB-MRI.

contrast-enhanced ultrasound

EOB-MRI is performed using standard dose of hepatocyte specific contrast media (primovist or eovist) according to standard protocol of our institution.

EOB-MRI

Jeong Min Lee, MD

This study aims to compare the diagnostic accuracy of Contrast-enhanced ultrasound (CEUS) for diagnosing hepatocellular carcinoma (HCC) with that of gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) using non-invasive diagnostic criteria (American Association for the Study of Liver Disease (AASLD or Liver Imaging Reporting and Data System (LI-RADS) v2018 and Korean Liver Cancer Study Group- National Cancer Center Korea (KLCSG-NCC) v2018).

Evaluation of Diagnostic Accuracy of CEUS for HCC Diagnosis

Evaluation of Diagnostic Accuracy of Contrast-enhanced Ultrasound (CEUS) and Gadoxetic Acid-enhanced Liver MRI for Diagnosis of Hepatocellular Carcinoma in Patients With Liver Cirrhosis

accuracy, sensitivity, specificity of CEUS for HCC diagnosis

accuracy, sensitivity, specificity of MRI using LI-RADS v2018 for HCC diagnosis

accuracy, sensitivity, specificity of MRI using KLCSG-NCC guideline v2018 for HCC diagnosis

Bracco Corporate

Seoul National University Hospital

Is a non comparative study. a magnetic resonance will be done using gadoxetic acid : 0.025mmol/Kg

all patients will have a magnetic resonance with gadobutrol as reference for diagnosis; in participants an additional magnetic resonance will be done with the new contrast agent to verify if the diagnostic can be done.

GADOXETIC ACID

Carmen Ayuso, Prof, PhD MD

This is a study to evaluate the primovist as a new contrast agent useful to diagnostic of hepatocellular carcinoma

The investigators plan to define the imaging patterns of hepatocellular carcinoma in cirrhotic patients when studied with gadoxetic acid magnetic resonance imaging including the dynamic phase and the hepatobiliary phase at 10 and 20 minutes after contrast injection and to evaluate the usefulness of liver magnetic resonance imaging with gadoxetic acid in the differentiation between benign and malignant nodules in the cirrhotic liver. To determine the diagnosis and clinical significance of the infracentimetric additional nodules detected in the hepatobiliary phase

Magnetic Resonance With Gadoxetic Acid for the Diagnosis of Hepatocellular Carcinoma in Patients With Liver Cirrhosis. Evaluation of Its Impact for the Non-invasive Diagnosis

Proportion of hepatocellular carcinoma diagnosed using gadoxetic acid magnetic resonance imaging (accuracy for diagnosis)

magnetic resonance imaging sensitivity - number of patients that need fine-needle biopsy to the diagnosis.

the patients would be followed until the diagnosis would be stablished. Is expected that this would be before 9 months.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gadoxetic Acid-enhanced MR Evaluation of Hepatocellular Carcinoma and Dysplastic Nodules in the Cirrhotic Liver	NCT01501240	Liver Cirrhosis Carcinoma, Hepa...		20 Years - 80 Years	Asan Medical Center
Gadoxetic Acid-MRI Versus Ultrasonography for the Surveillance of Hepatocellular Carcinoma in High-risk Patients	NCT01446666	Cirrhosis of Li...		20 Years -	Asan Medical Center
Gadoxetic Acid-MRI Versus Ultrasonography for the Surveillance of Hepatocellular Carcinoma in High-risk Patients	NCT01446666	Cirrhosis of Li...		20 Years -	Asan Medical Center
Evaluation of Diagnostic Accuracy of CEUS for HCC Diagnosis	NCT03742453	Hepatocellular ...	contrast-enhanc... EOB-MRI	20 Years -	Seoul National University Hospital
Magnetic Resonance With Gadoxetic Acid for the Diagnosis of Hepatocellular Carcinoma in Patients With Liver Cirrhosis. Evaluation of Its Impact for the Non-invasive Diagnosis	NCT01575574	Hepatocellular ...	GADOXETIC ACID	18 Years -	Fundacion Clinic per a la Recerca Biomédica
Gadoxetic Acid-enhanced MR Evaluation of Hepatocellular Carcinoma and Dysplastic Nodules in the Cirrhotic Liver	NCT01501240	Liver Cirrhosis Carcinoma, Hepa...		20 Years - 80 Years	Asan Medical Center
Gadoxetic Acid-enhanced MR Evaluation of Hepatocellular Carcinoma and Dysplastic Nodules in the Cirrhotic Liver	NCT01501240	Liver Cirrhosis Carcinoma, Hepa...		20 Years - 80 Years	Asan Medical Center
Magnetic Resonance With Gadoxetic Acid for the Diagnosis of Hepatocellular Carcinoma in Patients With Liver Cirrhosis. Evaluation of Its Impact for the Non-invasive Diagnosis	NCT01575574	Hepatocellular ...	GADOXETIC ACID	18 Years -	Fundacion Clinic per a la Recerca Biomédica

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