Hepatocyte-specific Versus Extracellular Contrast Agents for Liver MRI: Prospective, Intra-individual Comparison of Diagnostic Performance for Hepatocellular Carcinoma

Adult patients with chronic hepatitis B and cirrhosis of any etiology who are found to have suspected liver cancer are potentially eligible for the study. All enrolled patients will undergo two MRI scans using two different contrast agents. The type of contrast agent for the 1st MRI will be performed using hepatocyte-specific contrast agent. The participant will undergo the 2nd MRI using extracellular contrast agent. The MRI examinations will be independently interpreted by two different radiologists. The radiologists will evaluate focal hepatic lesions and categorize them according to the LI-RADS v2018 and EASL 2018. Once the diagnosis is made, the participants will be provided with the standard of care. After the initial treatment, the participants will be followed up with multi-phasic dynamic contrast-enhanced CT every 3 or 6 months for at least 2 years. Based on the prospectively written radiology reports, the diagnostic performances will be calculated and compared between MRI with hepatocyte-specific contrast agent and MRI with extracellular contrast agent, using the pathology and clinical criteria as the reference standard.

Study Overview

• Status: Unknown
• Conditions: Liver Cirrhosis; Chronic Hepatitis
• Intervention / Treatment: Other: hepatocyte-specific contrast agent, extracellular contrast agent

• Study Type: Interventional
• Enrollment (Anticipated): 129
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Older than 20 years

2. HBsAg (+) with chronic hepatitis or cirrhosis, anti-HCV (+) with cirrhosis, or cirrhosis of any etiology

   • The presence of cirrhosis will be determined based on the histologic or radiologic findings, including liver surface nodularity, margin blunting, segmental hypertrophy/atrophy, and findings secondary to portal hypertension (i.e., splenomegaly, esophageal or gastric varices, ascites, or reverse portal vein flow).
3. Child-Pugh class A or B

4. Up to three suspicious focal lesions between 10 mm and 30 mm found on US, CT, or MRI

   • Patients with a history of HCC treated by surgery or tumor ablation could be included, but only new nodules at a distance of > 2 cm from previously treated lesions were considered.

Exclusion Criteria:

1. Currently pregnant or lactating
2. Risk group for the use of gadolinium-enhanced MRI including severely decreased renal function (stage 4 or 5 chronic renal failure with eGFR ˂ 30 mL/min/1.73 m2), claustrophobia
3. Patients with history of chemoembolization or systemic treatment for liver cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: contrast agents for liver MRI	Other: hepatocyte-specific contrast agent, extracellular contrast agent; The type of contrast agent for the 1st MRI will be performed using hepatocyte-specific contrast agent (Primovist). The participant will undergo the 2nd MRI using extracellular contrast agent (Gadovist).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity	The comparison of sensitivity between MRI using hepatocyte-specific contrast agent and extracellular contrast agent in the diagnosis of hepatocellular carcinoma The per-lesion sensitivity will be compared using McNemar's test.	an expected average of 2 weeks
Specificity	The comparison of specificity between MRI using hepatocyte-specific contrast agent and extracellular contrast agent in the diagnosis of hepatocellular carcinoma. The per-lesion sensitivity will be compared using McNemar's test.	an expected average of 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inter-reader agreement between two radiologists	The inter-reader agreement between two radiologists for the LI-RADS v2018 categorization and diagnosis of HCC according to EASL 2018 in each MRI using hepatocyte-specific contrast agent and extracellular contrast agent. The inter-reader agreement will be evaluated using Cohen κ coefficient.	an expected average of 2 weeks

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2019
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: March 21, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2019
• Last Update Submitted That Met QC Criteria: March 25, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: HBsAg(+) with chronic hepatitis or cirrhosis; anti-HCV(+) with cirrhosis; cirrhosis of any etiology
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Fibrosis; Hepatitis; Carcinoma, Hepatocellular; Hepatitis, Chronic; Liver Cirrhosis
• Other Study ID Numbers: 4-2018-1047

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No