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



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.


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).


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).


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.


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



Alanine aminotransferase


Aspartate transaminase-to-platelet ratio index


Acoustic radiation force impulse


Aspartate aminotransferase


Cutoff index


Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid


Hepatitis B virus surface antigen


Hepatitis B virus


Hepatitis C virus


Hepatitis C virus antibody


Liver-to-major psoas muscle intensity ratio


Meters per second


Magnetic resonance imaging


Negative predictive value


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


Primary biliary cirrhosis


Positive predictive value


Receiver operating characteristic


Virtual Touch™ Tissue Quantification


Wisteria floribunda agglutinin-positive Mac-2 binding protein



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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