PIVKA-II Combined With Alpha-Fetoprotein for Diagnostic and Prognostic Value of Hepatic Tumors in Infants (PIVKA-II)

PIVKA-II Combined With Alpha-Fetoprotein for Diagnostic and Prognostic Value of Hepatic Tumors in Infants: Protocol for a Multicenter, Observational Study

Although hepatic tumors are uncommon in the perinatal period they are associated with significant morbidity and mortality in affected patients. The study is intended to evaluate the diagnostic efficiency of Protein Induced by Vitamin K Absence or antagonist-II(PIVKA-II) combining with alpha-fetoprotein in hepatic tumor of infant. This study is a multicenter study joined by several hospitals in China. Participants including hepatoblastoma, hepatic hemangioendothelioma and healthy control are consecutively recruited into the cohort. All the serum samples are collected before and after each treatment 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.

Study Overview

• Status: Completed
• Conditions: Hepatoblastoma; Hepatic Hemangioendothelioma
• Intervention / Treatment: Diagnostic test: PIVKA-II

Detailed Description

Hepatic tumors seldom occur in the perinatal period. They comprise approximately 5% of the total neoplasms of various types occurring in the fetus and neonate. Infantile hemangioendothelioma is the leading primary hepatic tumor followed by hepatoblastoma. Although alpha-fetoprotein has been well recognized as biomarker of hepatic tumors, it should be mentioned that this protein in normal infants is highly elevated during the first 2 months of life.

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. An elevated serum level of PIVKA-II is reported to be associated with hepatocellular (HCC). Many studies have shown that PIVKA-II is applicable for HCC surveillance and has been written into the guideline of JSH, which achieves remarkably good results.

The study is intended to evaluate diagnostic and differential diagnostic accuracy of PIVKA-II combining with alpha-fetoprotein in hepatic tumor of infant.

This study is a multicenter study joined by several hospitals in China. Participants including hepatoblastoma, hepatic hemangioendothelioma and healthy control. All the serum samples are collected before and after each treatment and will be tested in single center in order to decrease bias. Serum samples were tested for PIVKA-II, Alpha-fetoprotein(AFP)， and biochemical indexes including ALT, AST, GGT, AFU, etc. The diagnosis of hepatoblastoma and hepatic hemangioendothelioma was based on enhanced CT scanning and/or histopathology. 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 diagnostic and differential diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP.

• Study Type: Observational
• Enrollment (Actual): 257

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The participants will be recruited through inpatient department.

Description

Inclusion Criteria:

• Age between 1 month and 12 month
• Receiving no treatment before diagnosis
• With written informed consent

Exclusion Criteria:

• Clinical data missing
• Serum samples doesn't qualified
• Vitamin K absence

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
hepatoblastoma; The diagnosis of hepatoblastoma is based on enhanced CT scanning and/or histopathology.	Diagnostic test: PIVKA-II; Serum samples are tested for tumor markers including PIVKA-II, AFP, and biochemical tests.; Other Names: DCP
hepatic hemangioendothelioma; The diagnosis of hepatic hemangioendothelioma is based on enhanced CT scanning and/or histopathology.	Diagnostic test: PIVKA-II; Serum samples are tested for tumor markers including PIVKA-II, AFP, and biochemical tests.; Other Names: DCP
Healthy control; The healthy control group consist of people undergoing routine medical examination.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of PIVKA-II	Using PIVKA-II assay kit (ARCHITECT I2000SR REFURB, Abbott, America).	Baseline Time, Postoperative Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of AFP	Using the AFP assay (ARCHITECT AFP, Abbott, America).	Baseline Time, Postoperative Day 1

Collaborators and Investigators

• Sponsor: Shanghai Children's Medical Center
• Collaborators: The First Affiliated Hospital of Anhui Medical University; Zhengzhou Children's Hospital; Qilu Children's Hospital of Shandong University; Children's Hospital of Nanjing Medical University; Sun Yat-sen Memorial Hospital,Sun Yat-sen University; Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine; Chidren's Hospital of Fudan University; Chongqing Children's Hospital, Chongqing Medical University; Anhui Children's Hospital
• Investigators: Study Chair: Min Xu, Doctor, Shanghai Children's Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: August 20, 2018
• First Submitted That Met QC Criteria: August 22, 2018
• First Posted (Actual): August 24, 2018

Study Record Updates

• Last Update Posted (Actual): July 23, 2021
• Last Update Submitted That Met QC Criteria: July 16, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: infant; hepatoblastoma; Alpha-fetoprotein; Protein induced by vitamin K absence or antagonist-II; Differential diagnosis; Hepatic Hemangioendothelioma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplasms, Complex and Mixed; Hemangioma; Neoplasms, Vascular Tissue; Liver Neoplasms; Hepatoblastoma; Hemangioendothelioma
• Other Study ID Numbers: General surgery of SCMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No