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

Korea University

Status

Enrolling

Conditions

Surveillance

Liver Cirrhosis

Hepatocellular Carcinoma

Treatments

Diagnostic Test: Sonography

Diagnostic Test: CT

Diagnostic Test: AFP-L3

Diagnostic Test: PIVKA-II

Diagnostic Test: AFP

Study type

Interventional

Funder types

Other

Identifiers

NCT04414956

HCCAFPL3

Details and patient eligibility

About

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.

Full 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.

Enrollment

1,418 estimated patients

Sex

All

Ages

19 to 75 years old

Volunteers

No Healthy Volunteers

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