Combining Biomarkers (AFP, AFP-L3, and PIVKA-II) and Image Tools for Early Detection of Hepatocellular Carcinoma

May 30, 2020 updated by: Soon Ho Um, Korea University

Clinical Usefulness of Combining Biomarkers (AFP, AFP-L3, and PIVKA-II) With Abdominal Sonography or Computed Tomography for Early Detection of Hepatocellular Carcinoma

In this study, three biomarkers tests (AFP, AFP-L3 and PIVKA-II) and abdominal sonography or CT scans are performed every 6 months to detect hepatocellular carcinoma (HCC) early in patients with cirrhosis, a high-risk group of HCC. The aim of this study is to confirm the early HCC diagnosis rate in patients with cirrhosis and compare the detection efficacy between tests.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Early diagnosis of HCC is the most important factor in improving the prognosis of the disease. A surveillance test for early diagnosis of HCC in Korea is to perform alfa fetoprotein (AFP) and abdominal sonography every 6-months in high-risk groups. However, the detection rate of HCC using AFP and abdominal sonography is very low. There are several reports that the combination of the multiple biomarker tests including AFP, AFP L3, and PIVKA-II increased the early HCC detection only one test. Therefore, in the surveillance test for HCC, the combination of three tests with sonography would be helpful in the early diagnosis of HCC. However, there was few prospective large-scale studies about this issue.

Compared with abdominal sonography, contrast-enhanced CT or MRI is more useful in finding intrahepatic lesions of liver cirrhosis. However, there is no evidence data on combining sono/CT and biomarkers could improve the diagnosis for early HCC. Thus, it is essential to verify this prospectively in the real clinical practices to make recommendations based on a high level of evidence in the future. The investigators are conducting a prospective study which examines three biomarker tests and sonography every six months and contrast-enhanced CT annually for HCC surveillance in patients with cirrhosis.

Study Type

Interventional

Enrollment (Anticipated)

1418

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Korea, Republic of
      • Daegu, Korea, Republic of, 42601
        • Recruiting
        • Keimyung University Dongsan Medical Center
        • Contact:
          • Byoungkuk Jang
      • Seoul, Korea, Republic of, 08308
        • Recruiting
        • Korea University Guro Hospital
        • Contact:
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
          • Yunjoon Kim
      • Seoul, Korea, Republic of, 05505
        • Recruiting
        • Asan Medical Center
        • Contact:
          • Youngseok Yim
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Samsung Medical Center
        • Contact:
          • Yonghan Paik
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Severance Hospital
        • Contact:
          • Doyoung Kim
      • Seoul, Korea, Republic of, 02841
        • Recruiting
        • Korea University Anam Hospital
        • Contact:
      • Seoul, Korea, Republic of, 01757
        • Recruiting
        • Inje University Sanggye Paik Hospital
        • Contact:
      • Seoul, Korea, Republic of, 04401
        • Recruiting
        • SoonChunHyang University Seoul Hospital
        • Contact:
      • Seoul, Korea, Republic of, 05030
        • Recruiting
        • Konkuk University Hospital
        • Contact:
          • Wonhyeok Choe
      • Seoul, Korea, Republic of, 04763
        • Recruiting
        • Hanyang University Hospital
        • Contact:
          • Daewon Jun
      • Seoul, Korea, Republic of, 06591
        • Recruiting
        • The Catholic University of Korea Seoul St.Mary's Hospital
        • Contact:
          • Jeong Won Jang
      • Seoul, Korea, Republic of, 06973
        • Recruiting
        • Chung-Ang University Hosptial
        • Contact:
          • Hyungjoon Kim
    • Gyeonggi-do
      • Ansan, Gyeonggi-do, Korea, Republic of, 15355
        • Recruiting
        • Korea University Ansan Hospital
        • Contact:
        • Contact:
      • Uijeongbu, Gyeonggi-do, Korea, Republic of, 11765
        • Recruiting
        • The Catholic University of Korea Uijeongbu St.Mary's Hospital
        • Contact:
          • Changwook Kim

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with liver cirrhosis meeting one of the followings:

    i. Histologically confirmed liver cirrhosis ii. Imaging findings with liver cirrhosis (liver surface undulation, irregularity, or nodularity by US, CT, or MRI) plus one of followings: liver stiffness measurement ≥ 12.5 kilopascal, esophago-gastric varices, thrombocytopenia (<120,000/mm3), hypoalbuminemia (<3.5 g/dL), splenomegaly ≥12 cm) iii. Imaging findings with liver cirrhosis together with biomarkers suggesting liver cirrhosis (APRI ≥2.0 or fibrosis-4 ≥3.6) iv. Imaging findings with liver cirrhosis with history of hepatic decompensation (ascites, esophago-gastric variceal bleeding, jaundice, hepatic encephalopathy))

  • Expected survival more than 1 year
  • Child Pugh score 5-10 at the time of enrollment
  • Serum creatinine ≤1.5mg/dL
  • Age between 19 and 75 years old
  • No significant underlying medical illness affecting patient's survival
  • Patients available for regular follow-up according to the study protocol

Exclusion Criteria:

  • History of HCC
  • AFP >20 ng/mL
  • Hepatic nodule ≥ 1 cm by US or CT Exceptionally, nodules showing characteristic features of benign lesion such as hemangioma or pathologically conformed benign lesion are permitted for study inclusion.
  • Hepatic nodule less than 1 cm on US but imaging findings suggesting HCC by contrast enhanced US, CT, or MRI
  • Child-Pugh score ≥ 11
  • History of liver transplantation
  • Expecting liver transplantation within 1 year
  • Hypersensitivity on CT contrast dye
  • Any contraindication for CT
  • Not able to perform abdominal US
  • Other uncontrolled malignancy
  • Patients taking warfarin

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Surveillance
All participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually.
Diagnostic test: AFP-L3
AFP-L3 will be tested using serum sample every 6 months.
Other Names:
  • Lens culinaris agglutinin-reactive fraction of AFP
Diagnostic test: AFP
AFP will be tested using serum sample every 6 months.
Other Names:
  • Alpha fetoprotein
Diagnostic test: PIVKA-II
PIVKA-II will be tested using serum sample every 6 months.
Other Names:
  • Protein induced by vitamin K absence or antagonist-II
  • des-gamma-carboxy prothrombin
Diagnostic test: Sonography
Sonography will be tested by experts every 6 months.
Other Names:
  • Ultrasound
  • US
Diagnostic test: CT
Contrast-enhanced CT will be tested annually.
Other Names:
  • Computed tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HCC occurrence
Time Frame: 3 years after enrollment
Detection of HCC occurrence by three biomarkers and two image modalities
3 years after enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Early HCC occurrence
Time Frame: 3 years after enrollment
Detection of HCC less than 2cm
3 years after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Korea University

Collaborators

Samsung Medical Center
Asan Medical Center
Seoul National University Hospital
Korea University Anam Hospital
Korea University Guro Hospital
Chung-Ang University Hosptial, Chung-Ang University College of Medicine
Inje University
Hanyang University
The Catholic University of Korea
Severance Hospital
Keimyung University Dongsan Medical Center
Soonchunhyang University Hospital
Konkuk University Hospital
Korea University Ansan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2016

Primary Completion (Anticipated)

June 30, 2023

Study Completion (Anticipated)

February 28, 2026

Study Registration Dates

First Submitted

May 20, 2020

First Submitted That Met QC Criteria

May 30, 2020

First Posted (Actual)

June 4, 2020

Study Record Updates

Last Update Posted (Actual)

June 4, 2020

Last Update Submitted That Met QC Criteria

May 30, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HCCAFPL3

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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