Liver Cirrhosis, Hepatocellular Carcinoma, Surveillance
Conditions
Keywords
Liver Cirrhosis, Hepatocellular Carcinoma, Surveillance, AFP-L3, AFP, PIVKA-II, Sonography, CT
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.
Interventions
DIAGNOSTIC_TESTAFP
AFP will be tested using serum sample every 6 months.
DIAGNOSTIC_TESTPIVKA-II
PIVKA-II will be tested using serum sample every 6 months.
DIAGNOSTIC_TESTAFP-L3
AFP-L3 will be tested using serum sample every 6 months.
DIAGNOSTIC_TESTSonography
Sonography will be tested by experts every 6 months.
DIAGNOSTIC_TESTCT
Contrast-enhanced CT will be tested annually.
Sponsors
Korea University Ansan Hospital
Soonchunhyang University Hospital
Korea University Guro Hospital
The Catholic University of Korea
Samsung Medical Center
Asan Medical Center
Korea University Anam Hospital
Keimyung University Dongsan Medical Center
Severance Hospital
Hanyang University
Konkuk University Hospital
Seoul National University Hospital
Inje University
Chung-Ang University Hosptial, Chung-Ang University College of Medicine
Korea University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Intervention model description
Patients with cirrhosis will receive the surveillance test using three biomarker tests and sonography every six months and contrast-enhanced CT annually
Eligibility
Sex/Gender
ALL
Age
19 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HCC occurrence | 3 years after enrollment | Detection of HCC occurrence by three biomarkers and two image modalities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early HCC occurrence | 3 years after enrollment | Detection of HCC less than 2cm |
Countries
South Korea
Contacts
Primary ContactHyung Joon Yim, MD,PhD
Backup ContactSoon Ho Um, MD,PhD
Outcome results
None listed