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Journal of Gastroenterology

, Volume 50, Issue 1, pp 76–84 | Cite as

A novel serum marker, glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP), for assessing liver fibrosis

  • Takeo Toshima
  • Ken Shirabe
  • Toru Ikegami
  • Tomoharu Yoshizumi
  • Atsushi Kuno
  • Akira Togayachi
  • Masanori Gotoh
  • Hisashi Narimatsu
  • Masaaki Korenaga
  • Masashi Mizokami
  • Akihito Nishie
  • Shinichi Aishima
  • Yoshihiko Maehara
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

Recently, a novel marker, hyperglycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP), was developed for liver fibrosis using the glycan “sugar chain”-based immunoassay; however, the feasibility of WFA+-M2BP for assessing liver fibrosis has not been proven with clinical samples of hepatitis.

Methods

Serum WFA+-M2BP values were evaluated in 200 patients with chronic liver disease who underwent histological examination of liver fibrosis. The diagnostic accuracy of WFA+-M2BP values was compared with various fibrosis markers, such as ultrasound based-virtual touch tissue quantification (VTTQ), magnetic resonance imaging based-liver-to-major psoas muscle intensity ratio (LMR), and serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index (APRI).

Results

Serum WFA+-M2BP levels in patients with fibrosis grades F0, F1, F2, F3, and F4 had cutoff indices 1.62, 1.82, 3.02, 3.32, and 3.67, respectively, and there were significant differences between fibrosis stages F1 and F2, and between F2 and F3 (P < 0.01). The area under the receiver operating characteristic curves for the diagnosis of fibrosis (F ≥ 3) using serum WFA+-M2BP values (0.812) was almost comparable to that using VTTQ examination (0.814), but was superior to the other surrogate markers, including LMR index (0.766), APRI (0.694), hyaluronic acid (0.683), and type 4 collagen (0.625) (P < 0.01 each).

Conclusions

Serum WFA+-M2BP values based on a glycan-based immunoassay is an accurate, reliable, and reproducible method for the assessment of liver fibrosis. This approach could be clinically feasible for evaluation of beneficial therapy through the quantification of liver fibrosis in hepatitis patients if this measurement application is commercially realized.

Keywords

Liver fibrosis Chronic hepatitis M2BP Mac-2 binding protein VTTQ Fibrosis marker 

Abbreviations

ALT

Alanine aminotransferase

APRI

Aspartate transaminase-to-platelet ratio index

ARFI

Acoustic radiation force impulse

AST

Aspartate aminotransferase

COI

Cutoff index

Gd-EOB-DTPA

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid

HBsAg

Hepatitis B virus surface antigen

HBV

Hepatitis B virus

HCV

Hepatitis C virus

HCVAb

Hepatitis C virus antibody

LMR

Liver-to-major psoas muscle intensity ratio

m/s

Meters per second

MRI

Magnetic resonance imaging

NPV

Negative predictive value

nonBnonC

Negative for hepatitis B virus surface antigen and hepatitis C virus antibody

PBC

Primary biliary cirrhosis

PPV

Positive predictive value

ROC

Receiver operating characteristic

VTTQ

Virtual Touch™ Tissue Quantification

WFA+-M2BP

Wisteria floribunda agglutinin-positive Mac-2 binding protein

Notes

Acknowledgments

This study was supported by a Grant-in-Aid from the Ministry of Health, Labour and Welfare, Japan (H23-kannen-011). This research was performed by the Hepatitis Glyco-biomarker Study Group.

Conflict of interest

The authors declare that they have no conflict of interest and have no financial interests linked to this work.

Supplementary material

535_2014_946_MOESM1_ESM.pdf (96 kb)
Supplementary material 1 (PDF 96 kb)
535_2014_946_MOESM2_ESM.doc (60 kb)
Supplementary material 2 (DOC 59 kb)

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Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Takeo Toshima
    • 1
  • Ken Shirabe
    • 1
  • Toru Ikegami
    • 1
  • Tomoharu Yoshizumi
    • 1
  • Atsushi Kuno
    • 2
  • Akira Togayachi
    • 2
  • Masanori Gotoh
    • 2
  • Hisashi Narimatsu
    • 2
  • Masaaki Korenaga
    • 3
  • Masashi Mizokami
    • 3
  • Akihito Nishie
    • 4
  • Shinichi Aishima
    • 5
  • Yoshihiko Maehara
    • 1
  1. 1.Department of Surgery and Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Research Center for Medical Glycoscience (RCMG)National Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  3. 3.The Research Center for Hepatitis and ImmunologyNational Center for Global Health and MedicineIchikawaJapan
  4. 4.Department of Clinical Radiology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  5. 5.Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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