Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2021; 27(28): 4687-4696
Published online Jul 28, 2021. doi: 10.3748/wjg.v27.i28.4687
Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein improves diagnostic accuracy for hepatocellular carcinoma
Han Ah Lee, Yoo Ra Lee, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Hyunggin An, Hyung Joon Yim, Yoon Tae Jeen, Jong Eun Yeon, Kwan Soo Byun, Yeon Seok Seo
Han Ah Lee, Yoo Ra Lee, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Hyung Joon Yim, Yoon Tae Jeen, Jong Eun Yeon, Kwan Soo Byun, Yeon Seok Seo, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, South Korea
Hyunggin An, Department of Biostatistics, Korea University Anam Hospital, Seoul 02841, South Korea
Author contributions: Seo YS carried out the concept and design, provided administrative, technical or material support; Lee HA and Seo YS are responsible for methodology development, wrote, reviewed and/or revised the manuscript; Lee HA, Lee YR, Lee YS, Kim JH, An H, Yim HJ, Jeen YT, Yeon JE, Byun KS, and Seo YS retrograde data acquisition, analysis and interpretation; An H and Seo YS are responsible for learning supervision.
Institutional review board statement: This study protocol followed the ethical guidelines of the 1975 Declaration of Helsinki, and the institutional review board of Korea University Anam Medical Center.
Informed consent statement: The requirement for informed consent was waived owing to the retrospective nature of the study.
Conflict-of-interest statement: Authors have nothing to disclose.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at drseo@korea.ac.kr. Consent was not obtained but the presented data are anonymized and risk of identification is low.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yeon Seok Seo, MD, PhD, Professor, Department of Internal Medicine, Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, South Korea. drseo@korea.ac.kr
Received: January 27, 2021
Peer-review started: January 27, 2021
First decision: February 24, 2021
Revised: March 10, 2021
Accepted: July 13, 2021
Article in press: July 13, 2021
Published online: July 28, 2021
Processing time: 179 Days and 7 Hours
Abstract
BACKGROUND

Diagnostic accuracy of various tumor markers and their combinations for hepatocellular carcinoma (HCC) was not fully investigated.

AIM

To evaluate the diagnostic accuracy of alpha-fetoprotein (AFP), the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) and their combination for HCC diagnosis.

METHODS

Patients with newly detected liver mass or elevated serum AFP levels were considered eligible. Serum AFP level, AFP-L3 fraction, and PIVKA-II level were measured at the first visit.

RESULTS

In total, 622 patients were included; 355 patients (57.1%) had chronic liver disease, and 208 (33.4%) had liver cirrhosis. HCC was diagnosed in 160 patients (25.7%). The area under the receiver operating characteristics curves (AUROCs) of the serum AFP, AFP-L3 fraction, AFP-L3, and PIVKA-II levels for the diagnosis of HCC were 0.775, 0.792, 0.814, and 0.834, respectively. A novel diagnostic model was developed by classifying patients in a 1:1 ratio into training and validation sets. Using the binary regression analysis of the training cohort, the AFP, AFP-L3 fraction, and PIVKA-II (ALPs) score was calculated as follows: ALPs score = 3.8 × [serum AFP level (ng/mL) × AFP-L3 fraction (%) × 0.01] + 0.2 × PIVKA-II level (mAU/mL). The AUROC of the ALPs score for diagnosis of HCC was 0.878, significantly higher than that of serum AFP level (P < 0.001), AFP-L3 fraction (P < 0.001), PIVKA-II level (P = 0.036), and AFP-L3 level (P = 0.006). The optimal ALPs score cut-off was 5.3 (sensitivity, 85.0%, specificity 80.1%). The validation cohort showed similar results.

CONCLUSION

The ALPs score calculated using serum AFP level, AFP-L3 fraction, and PIVKA-II level showed improved accuracy in HCC diagnosis.

Keywords: Alpha-fetoprotein; Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein; Protein induced by vitamin K absence or antagonist-II; Hepatocellular carcinoma

Core Tip: The value of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) for improving diagnostic accuracy of hepatocellular carcinoma has not been fully evaluated. We investigated performance of AFP-L3 in patients with newly detected liver mass or elevated serum AFP level. In total of 622 patients, we observed significantly higher diagnostic accuracy of AFP-L3 level than with AFP level (P < 0.001). In addition, we developed a novel diagnostic model, AFP, AFP-L3 fraction, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) score, derived from AFP level, AFP-L3 fraction, and PIVKA-II level, and it showed significantly higher area under the receiver operating characteristics curves of 0.878 than those of AFP level, AFP-L3 fraction, and PIVKA-II level (all P < 0.05).