Clinical trial NCT04414956: Combining Biomarkers (AFP, AFP-L3, and PIVKA-II) and Image Tools for Early Detection of Hepatocellular Carcinoma
Official title: Clinical Usefulness of Combining Biomarkers (AFP, AFP-L3, and PIVKA-II) With Abdominal Sonography or Computed Tomography for Early Detection of Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Liver Cirrhosis
Hepatocellular Carcinoma
Surveillance
Keywords: Liver Cirrhosis
Hepatocellular Carcinoma
Surveillance
AFP-L3
AFP
PIVKA-II
Sonography
CT
Lead sponsor: Korea University
Sponsor class: OTHER
Collaborators: name: Korea University Ansan Hospital
name: Soonchunhyang University Hospital
name: Korea University Guro Hospital
name: The Catholic University of Korea
name: Samsung Medical Center
name: Asan Medical Center
name: Korea University Anam Hospital
name: Keimyung University Dongsan Medical Center
name: Severance Hospital
name: Hanyang University
name: Konkuk University Hospital
name: Seoul National University Hospital
name: Inje University
name: Chung-Ang University Hosptial, Chung-Ang University College of Medicine
First posted: 2020-06-04
Enrollment: 1418
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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
Primary purpose: SCREENING

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.

Eligibility criteria: 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

Primary outcomes:
measure: HCC occurrence
timeFrame: 3 years after enrollment
Secondary outcomes:
measure: Early HCC occurrence
timeFrame: 3 years after enrollment
Other outcomes:
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
state: Gyeonggi-do
city: Uijeongbu
country: Korea, Republic of
facility: The Catholic University of Korea Uijeongbu St.Mary's Hospital
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Seoul
country: Korea, Republic of
facility: Inje University SangGye Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Soonchunhyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St.Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hosptial
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
Study officials:
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