Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein as a Screening Tool for Significant Liver Fibrosis in Health Checkup.

Nobuharu Tamaki,Yuka Hayakawa,Masayuki Kurosaki,Yoshie Itakura,Hiroyuki Nakanishi,Kenta Takaura,Shuhei Sekiguchi,Rohit Loomba,Koji Yamashita,Kaoru Tsuchiya,Yuka Takahashi,Namiki Izumi,Leona Osawa,Shun Kaneko,Chiaki Maeyashiki,Kento Inada,Sakura Kirino,Yutaka Yasui,Jun Itakura,Masakazu Higuchi

doi:10.3390/ijms22010040

Abstract

Chronic liver disease is generally widespread, and a test for screening fibrotic subjects in a large population is needed. The ability of Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) to detect significant fibrosis was investigated in health checkup subjects in this research. Of 2021 health checkup subjects enrolled in this prospective cross-sectional study, those with WFA+-M2BP ≥ 1.0 were defined as high risk. Liver fibrosis was evaluated using magnetic resonance elastography (MRE) in subjects with high risk. The primary outcome was the positive predictive value (PPV) of WFA+-M2BP for significant fibrosis (liver stiffness ≥ 2.97 kPa by MRE). This trial was registered with the UMIN clinical trial registry, UMIN000036175. WFA+-M2BP ≥ 1.0 was observed in 5.3% of the 2021 subjects. The PPV for significant fibrosis with the threshold of WFA+-M2BP at ≥1.0, ≥1.1, ≥1.2, ≥1.3, ≥1.4, and ≥1.5 was 29.2%, 36.4%, 43.5%, 42.9%, 62.5%, and 71.4%, respectively. A WFA+-M2BP of 1.2 was selected as the optimal threshold for significant fibrosis among high-risk subjects, and the PPV, negative predictive value, sensitivity, and specificity for significant fibrosis were 43.5%, 84.0%, 71.4%, and 61.8%, respectively. WFA+-M2BP ≥ 1.2 was significantly associated with significant fibrosis, with an odds ratio (OR) of 4.04 (95% confidence interval (CI): 1.1–16, p = 0.04), but not FIB-4 ≥ 2.67 (OR: 2.40, 95%CI: 0.7–8.6, p-value = 0.2). In conclusion, WFA+-M2BP is associated with significant fibrosis and could narrow down potential subjects with liver fibrosis. The strategy of narrowing down fibrosis subjects using WFA+-M2BP may be used to screen for fibrotic subjects in a large population.

Highlights

Identification of subjects with liver fibrosis in chronic liver disease (CLD) is important because liver fibrosis strongly correlates with prognosis and mortality [1,2]
The co-existence of Hepatic stellate cells (HSCs) and Kupffer cells activates HSCs and increases alpha-smooth muscle actin expression. These findings indicate that WFA+-M2BP plays an important role in the progression of liver fibrosis, and WFA+-M2BP is associated with the fibrosis stage
When compared to subjects with WFA+-M2BP ≥ 1.0 and those with WFA+M2BP < 1.0, albumin levels and platelet counts were significantly lower in subjects with WFA+-M2BP ≥ 1.0, and the presence of diabetes mellitus was significantly higher in subjects with WFA+-M2BP ≥ 1.0

Summary

Introduction

Identification of subjects with liver fibrosis in chronic liver disease (CLD) is important because liver fibrosis strongly correlates with prognosis and mortality [1,2]. These subjects have no subjective symptoms, and early detection is difficult. As subjects with liver fibrosis must be identified from a large population, widely available modalities are needed to identify subjects with fibrosis. Serum biomarkers are widely used to evaluate liver fibrosis and prognosis in patients with CLD. In a first-line screening, serum biomarkers would be used to narrow down subjects with potential fibrosis, and imaging modalities or liver biopsy would be used as a second-line, more detailed test. The utility of serum markers for detecting or excluding subjects with fibrosis has been reported [5,6], most studies have been performed in hospital cohorts, and the utility of serum markers in a population-based cohort is limited, while a suitable serum marker for screening a population-based cohort has not yet been determined

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