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

NCT ID: NCT04414956

Last Updated: 2020-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

1418 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-01

Study Completion Date

2026-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Liver Cirrhosis Hepatocellular Carcinoma Surveillance

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Patients with cirrhosis will receive the surveillance test using three biomarker tests and sonography every six months and contrast-enhanced CT annually
Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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Surveillance

All participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually.

Group Type OTHER

AFP-L3

Intervention Type DIAGNOSTIC_TEST

AFP-L3 will be tested using serum sample every 6 months.

AFP

Intervention Type DIAGNOSTIC_TEST

AFP will be tested using serum sample every 6 months.

PIVKA-II

Intervention Type DIAGNOSTIC_TEST

PIVKA-II will be tested using serum sample every 6 months.

Sonography

Intervention Type DIAGNOSTIC_TEST

Sonography will be tested by experts every 6 months.

CT

Intervention Type DIAGNOSTIC_TEST

Contrast-enhanced CT will be tested annually.

Interventions

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AFP-L3

AFP-L3 will be tested using serum sample every 6 months.

Intervention Type DIAGNOSTIC_TEST

AFP

AFP will be tested using serum sample every 6 months.

Intervention Type DIAGNOSTIC_TEST

PIVKA-II

PIVKA-II will be tested using serum sample every 6 months.

Intervention Type DIAGNOSTIC_TEST

Sonography

Sonography will be tested by experts every 6 months.

Intervention Type DIAGNOSTIC_TEST

CT

Contrast-enhanced CT will be tested annually.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Lens culinaris agglutinin-reactive fraction of AFP Alpha fetoprotein Protein induced by vitamin K absence or antagonist-II des-gamma-carboxy prothrombin Ultrasound US Computed tomography

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Korea University Ansan Hospital

OTHER

Sponsor Role collaborator

Soonchunhyang University Hospital

OTHER

Sponsor Role collaborator

Korea University Guro Hospital

OTHER

Sponsor Role collaborator

The Catholic University of Korea

OTHER

Sponsor Role collaborator

Samsung Medical Center

OTHER

Sponsor Role collaborator

Asan Medical Center

OTHER

Sponsor Role collaborator

Korea University Anam Hospital

OTHER

Sponsor Role collaborator

Keimyung University Dongsan Medical Center

OTHER

Sponsor Role collaborator

Severance Hospital

OTHER

Sponsor Role collaborator

Hanyang University

OTHER

Sponsor Role collaborator

Konkuk University Hospital

OTHER

Sponsor Role collaborator

Seoul National University Hospital

OTHER

Sponsor Role collaborator

Inje University

OTHER

Sponsor Role collaborator

Chung-Ang University Hosptial, Chung-Ang University College of Medicine

OTHER

Sponsor Role collaborator

Korea University

OTHER

Sponsor Role lead

Responsible Party

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Soon Ho Um

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Korea University Ansan Hospital

Ansan, Gyeonggi-do, South Korea

Site Status RECRUITING

The Catholic University of Korea Uijeongbu St.Mary's Hospital

Uijeongbu-si, Gyeonggi-do, South Korea

Site Status RECRUITING

Keimyung University Dongsan Medical Center

Daegu, , South Korea

Site Status RECRUITING

Inje University SangGye Paik Hospital

Seoul, , South Korea

Site Status RECRUITING

Korea University Anam Hospital

Seoul, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital

Seoul, , South Korea

Site Status RECRUITING

Soonchunhyang University Seoul Hospital

Seoul, , South Korea

Site Status RECRUITING

Hanyang University Hospital

Seoul, , South Korea

Site Status RECRUITING

Konkuk University Hospital

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

The Catholic University of Korea Seoul St.Mary's Hospital

Seoul, , South Korea

Site Status RECRUITING

Chung-Ang University Hosptial

Seoul, , South Korea

Site Status RECRUITING

Korea University Guro Hospital

Seoul, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Hyung Joon Yim, MD,PhD

Role: CONTACT

+82-31-412-6565

Soon Ho Um, MD,PhD

Role: CONTACT

+82-2-920-5019

Facility Contacts

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Hyung Joon Yim

Role: primary

+82-31-412-6565

Tae Hyung Kim

Role: backup

+82-31-412-4832

Changwook Kim

Role: primary

Byoungkuk Jang

Role: primary

Eileen L. Yoon

Role: primary

Soon Ho Um

Role: primary

+82-2-920-6555

Yunjoon Kim

Role: primary

Doyoung Kim

Role: primary

Jae Young Jang

Role: primary

DaeWon Jun

Role: primary

Wonhyeok Choe

Role: primary

Youngseok Yim

Role: primary

Yonghan Paik

Role: primary

Jeong Won Jang

Role: primary

Hyungjoon Kim

Role: primary

Ji Hoon Kim

Role: primary

References

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El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011 Sep 22;365(12):1118-27. doi: 10.1056/NEJMra1001683. No abstract available.

Reference Type BACKGROUND
PMID: 21992124 (View on PubMed)

Korean Liver Cancer Study Group (KLCSG); National Cancer Center, Korea (NCC). 2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver. 2015 May 23;9(3):267-317. doi: 10.5009/gnl14460.

Reference Type BACKGROUND
PMID: 25918260 (View on PubMed)

Yim HJ, Suh SJ, Um SH. Current management of hepatocellular carcinoma: an Eastern perspective. World J Gastroenterol. 2015 Apr 7;21(13):3826-42. doi: 10.3748/wjg.v21.i13.3826.

Reference Type BACKGROUND
PMID: 25852267 (View on PubMed)

European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012 Apr;56(4):908-43. doi: 10.1016/j.jhep.2011.12.001. No abstract available.

Reference Type BACKGROUND
PMID: 22424438 (View on PubMed)

Yim SY, Seo YS, Jung CH, Kim TH, Lee JM, Kim ES, Keum B, Jong YK, An H, Kim JH, Yim HJ, Kim DS, Jeen YT, Yeon JE, Lee HS, Chun HJ, Byun KS, Um SH, Kim CD, Ryu HS. The management and prognosis of patients with hepatocellular carcinoma: what has changed in 20 years? Liver Int. 2016 Mar;36(3):445-53. doi: 10.1111/liv.12960. Epub 2015 Oct 12.

Reference Type RESULT
PMID: 26352789 (View on PubMed)

Sterling RK, Jeffers L, Gordon F, Venook AP, Reddy KR, Satomura S, Kanke F, Schwartz ME, Sherman M. Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2009 Jan;7(1):104-13. doi: 10.1016/j.cgh.2008.08.041. Epub 2008 Sep 17.

Reference Type RESULT
PMID: 18849011 (View on PubMed)

Taketa K, Sekiya C, Namiki M, Akamatsu K, Ohta Y, Endo Y, Kosaka K. Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions. Gastroenterology. 1990 Aug;99(2):508-18. doi: 10.1016/0016-5085(90)91034-4.

Reference Type RESULT
PMID: 1694805 (View on PubMed)

Taketa K, Endo Y, Sekiya C, Tanikawa K, Koji T, Taga H, Satomura S, Matsuura S, Kawai T, Hirai H. A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma. Cancer Res. 1993 Nov 15;53(22):5419-23.

Reference Type RESULT
PMID: 7693340 (View on PubMed)

Oka H, Saito A, Ito K, Kumada T, Satomura S, Kasugai H, Osaki Y, Seki T, Kudo M, Tanaka M; Collaborative Hepato-Oncology Study Group of Japan. Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein. J Gastroenterol Hepatol. 2001 Dec;16(12):1378-83. doi: 10.1046/j.1440-1746.2001.02643.x.

Reference Type RESULT
PMID: 11851836 (View on PubMed)

Nakamura S, Nouso K, Sakaguchi K, Ito YM, Ohashi Y, Kobayashi Y, Toshikuni N, Tanaka H, Miyake Y, Matsumoto E, Shiratori Y. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006 Sep;101(9):2038-43. doi: 10.1111/j.1572-0241.2006.00681.x. Epub 2006 Jul 18.

Reference Type RESULT
PMID: 16848811 (View on PubMed)

Choi JY, Jung SW, Kim HY, Kim M, Kim Y, Kim DG, Oh EJ. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol. 2013 Jan 21;19(3):339-46. doi: 10.3748/wjg.v19.i3.339.

Reference Type RESULT
PMID: 23372355 (View on PubMed)

Yoon YJ, Han KH, Kim DY. Role of serum prothrombin induced by vitamin K absence or antagonist-II in the early detection of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Scand J Gastroenterol. 2009;44(7):861-6. doi: 10.1080/00365520902903034.

Reference Type RESULT
PMID: 19391065 (View on PubMed)

Seo SI, Kim HS, Kim WJ, Shin WG, Kim DJ, Kim KH, Jang MK, Lee JH, Kim JS, Kim HY, Kim DJ, Lee MS, Park CK. Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol. 2015 Apr 7;21(13):3928-35. doi: 10.3748/wjg.v21.i13.3928.

Reference Type RESULT
PMID: 25852278 (View on PubMed)

Lim TS, Kim DY, Han KH, Kim HS, Shin SH, Jung KS, Kim BK, Kim SU, Park JY, Ahn SH. Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients. Scand J Gastroenterol. 2016 Mar;51(3):344-53. doi: 10.3109/00365521.2015.1082190. Epub 2015 Sep 4.

Reference Type RESULT
PMID: 26340708 (View on PubMed)

Di Martino M, De Filippis G, De Santis A, Geiger D, Del Monte M, Lombardo CV, Rossi M, Corradini SG, Mennini G, Catalano C. Hepatocellular carcinoma in cirrhotic patients: prospective comparison of US, CT and MR imaging. Eur Radiol. 2013 Apr;23(4):887-96. doi: 10.1007/s00330-012-2691-z. Epub 2012 Nov 18.

Reference Type RESULT
PMID: 23179521 (View on PubMed)

Kudo M, Matsui O, Izumi N, Iijima H, Kadoya M, Imai Y, Okusaka T, Miyayama S, Tsuchiya K, Ueshima K, Hiraoka A, Ikeda M, Ogasawara S, Yamashita T, Minami T, Yamakado K; Liver Cancer Study Group of Japan. JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer. 2014 Oct;3(3-4):458-68. doi: 10.1159/000343875.

Reference Type RESULT
PMID: 26280007 (View on PubMed)

Chou R, Cuevas C, Fu R, Devine B, Wasson N, Ginsburg A, Zakher B, Pappas M, Graham E, Sullivan SD. Imaging Techniques for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 May 19;162(10):697-711. doi: 10.7326/M14-2509.

Reference Type RESULT
PMID: 25984845 (View on PubMed)

Other Identifiers

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HCCAFPL3

Identifier Type: -

Identifier Source: org_study_id

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