Copyright
©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin
Xiang-Jun Qian, Zhu-Mei Wen, Xiao-Ming Huang, Hui-Juan Feng, Shan-Shan Lin, Yan-Na Liu, Sheng-Cong Li, Yu Zhang, Wen-Guang Peng, Jia-Rui Yang, Zhe-Yu Zheng, Lei Zhang, Da-Wei Zhang, Feng-Min Lu, Li-Juan Liu, Wei-Dong Pan
Xiang-Jun Qian, Xiao-Ming Huang, Wen-Guang Peng, Jia-Rui Yang, Zhe-Yu Zheng, Lei Zhang, Da-Wei Zhang, Wei-Dong Pan, Department of Pancreatic Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
Xiang-Jun Qian, Yan-Na Liu, Feng-Min Lu, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Zhu-Mei Wen, Hui-Juan Feng, Sheng-Cong Li, Yu Zhang, Li-Juan Liu, Department of Laboratory Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, Fujian Province, China
Shan-Shan Lin, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, United States
Author contributions: Qian XJ, Wen ZM, and Huang XM contributed to acquisition of data, analysis and interpretation of data, drafting of the manuscript, and statistical analysis; Feng HJ, Li SC, Zhang Y, Peng WG, Yang JR, Zheng ZY, and Zhang L contributed to acquisition of data and critical revision of the manuscript for important intellectual content; Lin SS, Liu YN, and Zhang DW contributed to administrative, technical, material support, and critical revision of the manuscript for important intellectual content; Lu FM, Liu LJ, and Pan WD contributed to study concept and design, obtained funding and material support, study supervision and critical revision of the manuscript for important intellectual content; all authors of this research have approved the final version of the article; Qian XJ, Wen ZM, and Huang XM contributed equally to this work; Lu FM, Liu LJ, and Pan WD contributed equally to this work.
Supported by the National Key Clinical Discipline, Fuzhou “14th Five-Year Plan” Clinical Key Specialty (laboratory medicine) and the National Science Foundation of China, No. 82002587.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Peking University Health Science Center (Approval No. IRB00001052-19081).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The datasets analyzed during the current study are available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Wei-Dong Pan, MD, Doctor, Professor, Surgeon, Department of Pancreatic Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, No. 26 Erheng Road, Tianhe District, Guangzhou 510655, Guangdong Province, China.
panwd@mail.sysu.edu.cn
Received: November 16, 2022
Peer-review started: November 16, 2022
First decision: December 11, 2022
Revised: December 30, 2022
Accepted: February 16, 2023
Article in press: February 16, 2023
Published online: February 28, 2023
Processing time: 103 Days and 19.8 Hours
BACKGROUND
Serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) is a promising biomarker for hepatocellular carcinoma (HCC) surveillance.
AIM
To identify the contributing factors related to the abnormal elevation of PIVKA-II level and assess their potential influence on the performance of PIVKA-II in detecting HCC.
METHODS
This study retrospectively enrolled in 784 chronic liver disease (CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve (AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-II for HCC, respectively.
RESULTS
Elevated PIVKA-II levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase (ALP), and total bilirubin (TBIL) for CLD patients and aspartate aminotransferase (AST) and tumor size for HCC patients (all P < 0.05). Serum PIVKA-II were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal (ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST (all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-II was significantly higher compared to that in patients with TBIL > 1 × ULN (0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant (0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.
CONCLUSION
Serum PIVKA-II has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.
Core Tip: This study demonstrated that elevated serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) were positively associated with serum total bilirubin (TBIL) in patients with chronic liver disease (CLD), and the levels of PIVKA-II in CLD patients with normal serum TBIL were significantly lower than those in CLD patients with abnormal serum TBIL. Serum PIVKA-II has better performance in detecting hepatocellular carcinoma (HCC) at an early stage for CLD patients with normal serum TBIL, which was more prominently perceived in patients with viral etiology and hepatitis B virus alone. These findings may be important for surveillance counseling of early-stage HCC.
