Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein more reliably distinguishes liver fibrosis stages in non-alcoholic fatty liver disease than serum Mac-2 binding protein

Masanori Atsukawa; Akihito Tsubota; Tomomi Okubo; Taeang Arai; Ai Nakagawa; Norio Itokawa; Chisa Kondo; Keizo Kato; Tsutomu Hatori; Hiroshi Hano; Tsunekazu Oikawa; Naoya Emoto; Masanori Abe; Masayoshi Kage; Katsuhiko Iwakiri

doi:10.1111/hepr.13046

Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein more reliably distinguishes liver fibrosis stages in non-alcoholic fatty liver disease than serum Mac-2 binding protein

Hepatol Res. 2018 May;48(6):424-432. doi: 10.1111/hepr.13046. Epub 2018 Jan 10.

Authors

Masanori Atsukawa^{1

2}, Akihito Tsubota³, Tomomi Okubo¹, Taeang Arai¹, Ai Nakagawa¹, Norio Itokawa¹, Chisa Kondo¹, Keizo Kato⁴, Tsutomu Hatori⁵, Hiroshi Hano⁶, Tsunekazu Oikawa⁷, Naoya Emoto⁸, Masanori Abe⁹, Masayoshi Kage¹⁰, Katsuhiko Iwakiri²

Affiliations

¹ Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
² Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan.
³ Core Research Facilities for Basic Science, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
⁴ Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba, Japan.
⁵ Department of Pathology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
⁶ Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
⁷ Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, Japan.
⁸ Department of Internal Medicine, Division of Endocrinology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
⁹ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
¹⁰ Molecular Targeting Therapeutics Division, Research Center for Innovative Cancer Therapy, Kurume University, Fukuoka, Japan.

PMID: 29274190
DOI: 10.1111/hepr.13046

Abstract

Aim: Serum Mac-2 binding protein (M2BP) and Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA⁺ -M2BP) are used to estimate the liver fibrosis stage in chronic liver diseases. However, few head-to-head studies have been carried out to compare the two biomarkers in non-alcoholic fatty liver disease (NAFLD).

Methods: Serum M2BP and WFA⁺ -M2BP levels were compared against clinical characteristics and liver histological manifestations in the same samples collected from 213 biopsy-proven NAFLD patients.

Results: Median levels (range) of M2BP and WFA⁺ -M2BP were 1.58 (0.70-7.75) pg/mL and 0.85 (0.22-11.32) cut-off index (COI), respectively. Fibrosis stages 1, 2, 3, and 4 were determined in 136, 37, 17, and 23 patients, respectively. Median levels of both biomarkers increased stepwise with fibrosis progression. The M2BP and WFA⁺ -M2BP levels showed a significant positive correlation (r = 0.643, P = 2.91 × 10^-26 ), but a marked discrepancy between both biomarkers was noted in five stage 4 and three stage 1 patients, who had high WFA⁺ -M2BP but relatively low M2BP levels. Most of these outliers had findings suggestive of more advanced fibrosis. For diagnosing any fibrosis severity, WFA⁺ -M2BP had greater area under the receiver operating characteristic curve (AUC) and predictive accuracy than M2BP. Among eight fibrosis markers/indices, WFA⁺ -M2BP yielded the second highest AUC (0.832) and the highest predictive accuracy (82.2%) to diagnose cirrhosis. In addition, WFA⁺ -M2BP showed the second highest predictive accuracy to diagnose severe fibrosis (78.4%) and significant fibrosis (76.1%).

Conclusion: This head-to-head comparison suggests that WFA⁺ -M2BP is superior to M2BP for distinguishing liver fibrosis stages in NAFLD patients. A marked discrepancy between the two biomarkers may be indicative of advanced NAFLD (UMIN000023286).

Keywords: Mac-2BP; WFA+-Mac-2BP; fibrosis; liver cirrhosis; non-alcoholic fatty liver disease.