title: Serum Mac-2 binding protein levels as a novel diagnostic biomarker for prediction of disease severity and nonalcoholic steatohepatitis.
abstract: OBJECTIVE
  Mac-2 binding protein (Mac-2 bp) is one of the major fucosylated glycoproteins, which we identified with glycol-proteomic analyses. We previously reported that fucosylated glycoproteins are secreted into bile, but scarcely secreted into sera in normal liver and hypothesized that the fucosylation-based sorting machinery would be disrupted in ballooning hepatocytes due to the loss of cellular polarity. In the present study, we investigated the availability of Mac-2 bp for differential diagnosis of nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD) as a biomarker.
  
  
  METHODS
  Serum Mac-2 bp levels were determined with our developed ELISA kit. Our cohort of 127 patients with NAFLD had liver biopsy to make a histological diagnosis of NASH and simple fatty liver.
  
  
  RESULTS
  Mac-2 bp levels were significantly elevated in NASH patients compared with non-NASH (simple steatosis) patients (2.132 ± 1.237 vs. 1.103 ± 0.500 μg/mL, p < 0.01). The area under the receiver-operating characteristic curve for predicting NASH by Mac-2 bp was 0.816. Moreover, multivariate logistic regression analyses showed Mac-2 bp levels could predict the fibrosis stage and the presence of ballooning hepatocytes in NAFLD patients.
  
  
  CONCLUSIONS
  These results support the potential usefulness of measuring Mac-2 bp levels in clinical practice as a biomarker for NASH.
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.|Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Abeno-ku, Osaka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Gastroenterology, Ikeda Municipal Hospital, Ikeda, Osaka, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sawai
authors.affiliation: Department of Gastroenterology, Otemae Hospital, Osaka, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Doi
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.|Department of Surgery, Matsumoto Hospital, Kakogawa, Hyogo, Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Uozumi
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Mizutani
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Maaya
authors.initials: M
authors.lastname: Akita
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Motoya
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Sachiho
authors.initials: S
authors.lastname: Kida
authors.affiliation: Immuno-Biological Laboratories, Fujioka, Gunma, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kinoshita
authors.affiliation: Immuno-Biological Laboratories, Fujioka, Gunma, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Maruyama
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yakushijin
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ezaki
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kiso
authors.affiliation: Department of Gastroenterology, Ikeda Municipal Hospital, Ikeda, Osaka, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Imai
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Abeno-ku, Osaka, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.affiliation: Department of Molecular Biochemistry & Clinical Investigation, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D005643:Fucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000175:diagnosis*; D011379:Prognosis
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D008562:Membrane Glycoproteins; C114782:TAA90K protein, human; D005643:Fucose
keywords: Ballooning hepatocyte; Liver fibrosis; Mac-2bp/90K; N-glycan; NASH/NAFLD