Combining Biomarkers (AFP, AFP-L3, and PIVKA-II) and Image Tools for Early Detection of Hepatocellular Carcinoma
- Conditions
- SurveillanceHepatocellular CarcinomaLiver Cirrhosis
- Interventions
- Diagnostic Test: AFP-L3Diagnostic Test: AFPDiagnostic Test: PIVKA-IIDiagnostic Test: SonographyDiagnostic Test: CT
- Registration Number
- NCT04414956
- Lead Sponsor
- Korea University
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1418
-
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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Surveillance AFP-L3 All participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually. Surveillance AFP All participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually. Surveillance Sonography All participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually. Surveillance CT All participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually. Surveillance PIVKA-II All participants will be examined with three biomarker tests and sonography every six months and contrast-enhanced CT annually.
- Primary Outcome Measures
Name Time Method HCC occurrence 3 years after enrollment Detection of HCC occurrence by three biomarkers and two image modalities
- Secondary Outcome Measures
Name Time Method Early HCC occurrence 3 years after enrollment Detection of HCC less than 2cm
Trial Locations
- Locations (15)
Korea University Ansan Hospital
🇰🇷Ansan, Gyeonggi-do, Korea, Republic of
The Catholic University of Korea Uijeongbu St.Mary's Hospital
🇰🇷Uijeongbu, Gyeonggi-do, Korea, Republic of
Inje University SangGye Paik Hospital
🇰🇷Seoul, Korea, Republic of
Soonchunhyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Konkuk University Hospital
🇰🇷Seoul, Korea, Republic of
Hanyang University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Chung-Ang University Hosptial
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St.Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of