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 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:
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.
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
Research background

Identifying useful biomarkers to diagnose hepatocellular carcinoma (HCC) remains important priority in clinical research. Recently, various tumor markers including protein induced by vitamin K absence or antagonist-II (PIVKA-II), and novel blood parameter, the Lens culinaris agglutinin- reactive fraction of alpha-fetoprotein (AFP-L3), have been introduced and evaluated.

Research motivation

Several studies showed improved HCC diagnostic ability of the combination of AFP, AFP-L3, and PIVKA-II, than either AFP or PIVKA-II. However, because of the small sample size and the specific characteristics of the study population, conflicting results have been reported.

Research objectives

We aimed to investigate and compare the predictive ability of AFP, AFP-L3, and PIVKA-II as well as their combination for HCC diagnosis in this retrospective study with a large number of patients. Further, we developed and validated a new diagnostic model for HCC.

Research methods

Patients referred from primary clinics to the Korea University Medical Center for newly noted space occupying lesion in liver or elevated serum AFP level between 2015 and 2019 were enrolled. Their serum AFP level, AFP-L3 fraction, and PIVKA-II level were measured in blood samples collected at their first visit.

Research results

It was observed that AFP-L3 level exhibited a considerably higher diagnostic accuracy than with AFP level (P < 0.001). In addition, a novel diagnostic model for HCC, ALPs score, derived from the AFP level, AFP-L3 fraction, and PIVKA-II level showed highest area under the receiver operating characteristics curves of 0.878 for HCC diagnosis. It was significantly higher than those of the AFP level, AFP-L3 fraction, and PIVKA-II level (all P < 0.05).

Research conclusions

Finally, AFP-L3 level, calculated by multiplying the AFP level with the AFP-L3 fraction had a significantly higher diagnostic ability than the AFP level for HCC diagnosis. The novel diagnostic model, ALPs score was more valuable compared to individual tumor markers for HCC diagnosis.

Research perspectives

Further studies including patients with specific liver disease and studies for external validation and cost-effectiveness are required.