Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 21, 2013; 19(3): 339-346
Published online Jan 21, 2013. doi: 10.3748/wjg.v19.i3.339
Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP
Jong Young Choi, Seung Won Jung, Hee Yeon Kim, Myungshin Kim, Yonggoo Kim, Dong Goo Kim, Eun-Jee Oh
Jong Young Choi, Hee Yeon Kim, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea
Seung Won Jung, Myungshin Kim, Yonggoo Kim, Eun-Jee Oh, Department of Laboratory Medicine and Laboratory Development Evaluation Center, School of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea
Dong Goo Kim, Department of Surgery, School of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea
Author contributions: Choi JY and Jung SW contributed equally to the work; Choi JY and Oh EJ designed the research; Jung SW performed the majority of experiments; Kim HY, Kim M and Kim Y provided analytical tools and were also involved in editing the manuscript; Choi JY and Kim DG provided the collection of all the human material for this work; Choi JY and Oh EJ wrote the manuscript.
Supported by The Industrial Core Technology Development Program funded by the Ministry of Knowledge Economy, No. 10033183
Correspondence to: Dr. Eun-Jee Oh, Department of Laboratory Medicine and Laboratory Development Evaluation Center, School of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul 137-701, South Korea. ejoh@catholic.ac.kr
Telephone: +82-2-22581641 Fax: +82-2-22581719
Received: July 16, 2012
Revised: October 25, 2012
Accepted: November 6, 2012
Published online: January 21, 2013
Processing time: 189 Days and 7.8 Hours
Abstract

AIM: To evaluate diagnostic value of α-fetoprotein (AFP)-L3 and prothrombin induced by vitamin K absence-II (PIVKA-II) in hepatocellular carcinoma (HCC).

METHODS: One hundred and sixty-eight patients during routine HCC surveillance were included in this study. Of the 168 patients, 90 (53.6%) had HCC including newly developed HCC (n = 82) or recurrent HCC after treatment (n = 8). Sera were obtained during their first evaluation for HCC development and at the time of HCC diagnosis before commencing HCC treatment. HCC was diagnosed by histological examination, appropriate imaging characteristics-computed tomography or magnetic resonance imaging. Control sera were collected from 78 patients with benign liver disease (BLD), which were obtained during routine surveillance with a suspicion of HCC. AFP, AFP-L3 and PIVKA-II were measured in the same serum by microchip capillary electrophoresis and liquid-phase binding assay on a micro-total analysis system Wako i30 auto analyzer. The performance characteristics of three tests and combined tests for the diagnosis of HCC were obtained using receiver operating characteristic curves in all populations and subgroups with AFP < 20 ng/mL.

RESULTS: Of 90 HCC patients, 38 (42.2%) patients had AFP < 20 ng/mL, 20 (22.2%) patients had AFP 20-200 ng/mL and 32 (35.6%) patients had AFP > 200 ng/mL. Of the 78 BLD patients, 74 (94.9%) patients had AFP < 20 ng/mL. After adjustment for age and HBV infection status, AFP-L3 levels were higher in HCC than in BLD among patients with low AFP levels (< 20 ng/mL) (P < 0.001). In a total of 168 patients, areas under the curve (AUC) for HCC were 0.879, 0.887, 0.801 and 0.939 for AFP, AFP-L3, PIVKA-II and the combined markers, respectively. The combined AUC for three markers showed higher value than the AUCs of individual marker (P < 0.05). AFP-L3 had higher AUC value than PIVKA-II for HCC detection in entire patients (P = 0.043). With combination of AFP-L3 (cut-off > 5%) and PIVKA-II (cut-off > 40 AU/L), the sensitivity were 94.4% and specificity were 75.6% in all patients. In 112 patients with low AFP levels (< 20 ng/mL), AUCs of AFP-L3, PIVKA-II and combine AFP-L3 and PIVKA-II tests were 0.824, 0.774 and 0.939, respectively. AFP-L3 with a cut-off value of 5% showed sensitivity of 71.1% and specificity of 83.8%, and PIVKA-II with a cut-off value of 40 AU/L had sensitivity of 57.9% and specificity of 95.9% in patients with low AFP levels. The combination of AFP-L3 and PIVKA-II increased the sensitivity and specificity up to 92.1% and 79.7%, respectively, in low AFP group. Combined markers detected 81.8% of early stage HCC (Union for International Cancer Control stage I), 86.7% of small sized tumor (< 2 cm) and 91.7% of single tumor of HCC in the low AFP group. In multivariate analysis, AFP-L3 was correlated with AFP and tumor size, and PIVKA-II was correlated with laboratory tests including serum aspartate aminotransferase, total bilirubin, platelets and albumin levels. PIVKA-II had no correlation with AFP, AFP-L3 or tumor characteristics.

CONCLUSION: Combined determination of AFP-L3 and PIVKA-II could improve the diagnostic value for HCC detection in patients with or without increased AFP levels.

Keywords: α-fetoprotein; Prothrombin induced by vitamin K absence-II; Hepatocellular carcinoma; Diagnosis; Tumor marker