Evaluation of Diagnostic Efficiency of PIVKA-II and Other Tumor Markers in HCC

Study Overview
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Brief Summary
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The incidence of Hepatocellular carcinoma (HCC) is increasing worldwide. However, most of HCC cases were at advanced stage when the diagnosis established.Early diagnosis improves the prognosis.The study is intended to evaluate the diagnostic efficiency of Protein Induced by Vitamin K Absence or antagonist-II(PIVKA-II). This study is a international multicenter study joined by several hospitals in China,Singapore,Thailand and Vietnam. Participants including healthy control,HCC,metastatic liver cancer,Hepatitis B virus(HBV) and liver cirrhosis are consecutively recruited into the cohort. All the serum samples are collected before any treatments and will be tested in single center in order to decrease bias. Serum samples were tested for PIVKA-II,alpha-fetoprotein and biochemical indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT),alpha-l-fucosidase(AFU),etc.

Detailed Description
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Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide.Early diagnosis improves the prognosis. Protein induced by vitamin K antagonist-II (PIVKA-II), also known as des-γ-carboxyprothrombin (DCP) or acarboxy prothrombin, is an abnormal form of prothrombin induced by vitamin K absence or antagonist-II. The study is intended to evaluate the diagnostic efficiency of Protein Induced by Vitamin K Absence or antagonist-II(PIVKA-II). PIVKA-II as an effective tumor marker for hepatocellular carcinoma(HCC) has been widely used in the western countries where most cases are hepatitis C virus(HCV) related.However, the majority of HCCs in China are HBV related. Despite the extensive application of PIVKA-II in some hospitals from China, the diagnostic efficiency including sensitivity,specificity,positive predictive value and negative predictive value still needs more clinical data to evaluate. The research purposes list as follows：1.Determination of diagnostic Cut-off value 2.Evaluation of diagnostic efficiency of PIVKA-II 3.Evaluation of the combination of PIVKA-II and other tumor markers for HCC. This study is an international multicenter study joined by several hospitals in China,Singapore,Thailand and Vietnam. Participants including healthy control,HCC,metastatic liver cancer,HBV and liver cirrhosis are consecutively recruited into the cohort. All the serum samples are collected before any treatments and will be tested in single center in order to decrease bias. Serum samples were tested for PIVKA-II,Alpha-fetoprotein(AFP)，alpha-fetoprotein L3 and biochemical indexes including ALT,AST,GGT,AFU,etc. The diagnosis of HCC was based on histopathology. All HCC diagnoses were confirmed at the time of analysis.The Student's t-test (or Mann-Whitney test) was used to compare continuous variables, and the chi-square test (or Fisher's exact test) was used for categorical variables. A receiver operator characteristic (ROC) curve was used to assess the performance characteristic of PIVKA-II,AFP,AFP-L3 measurement.

Official Title
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Evaluation of Diagnostic and Differential Diagnostic Significance of a Combination of PIVKA-II and Other Tumor Markers in Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Diagnostic Test: PIVKA-II


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 85 Receiving no treatment before diagnosis Establishing Diagnosis according to the Asian Pacific Association for the Study of Liver(APASL) criteria Exclusion Criteria: Clinical data missing Laboratory tests information missing Serum samples doesn't qualified Obstructive jaundice patients Medical history of taking warfarin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy control<br>The healthy control group consist of people undergoing routine medical examination. Serum samples are collected. | Diagnostic Test: PIVKA-II<br>* Serum samples are tested for tumor markers including PIVKA-II,AFP,AFP-L3% and biochemical tests.<br>* Other names: DCP;|
| Metastatic liver cancer patients<br>Serum samples are collected. | Diagnostic Test: PIVKA-II<br>* Serum samples are tested for tumor markers including PIVKA-II,AFP,AFP-L3% and biochemical tests.<br>* Other names: DCP;|
| Hepatocellular carcinoma patients<br>Serum samples are collected before liver resection. | Diagnostic Test: PIVKA-II<br>* Serum samples are tested for tumor markers including PIVKA-II,AFP,AFP-L3% and biochemical tests.<br>* Other names: DCP;|
| Chronic liver disease patients<br>This group is comprised of liver cirrhosis and chronic hepatitis B patients. The diagnosis of liver cirrhosis are based on triple-phase contrast enhanced computed tomography, magnetic resonance imaging. | Diagnostic Test: PIVKA-II<br>* Serum samples are tested for tumor markers including PIVKA-II,AFP,AFP-L3% and biochemical tests.<br>* Other names: DCP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PIVKA-II | Using PIVKA-II assay kit(chemiluminescent microparticle immunoassay). | Day one | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AFP,AFP-L3% |  | Day one | 
| ALT, AST，γ-GT， AFU |  | Day one | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alpha-fetoprotein, Hepatocellular carcinoma, Protein induced by vitamin K absence or antagonist-II, Differential diagnosis, Des-γ-carboxy prothrombin, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein-fetoprotein