title: Evaluation of Fucosylated Haptoglobin and Mac-2 Binding Protein as Serum Biomarkers to Estimate Liver Fibrosis in Patients with Chronic Hepatitis C.
abstract: Fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac-2 bp) are identified as cancer biomarkers, based on the results from a glyco-proteomic analysis. Recently, we reported that these glyco-biomarkers were associated with liver fibrosis and/or ballooning hepatocytes in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the ability of these glycoproteins to estimate liver fibrosis in 317 patients with chronic hepatitis C. We measured the serum Fuc-Hpt and Mac-2 bp levels using a lectin-antibody ELISA and ELISA, respectively. The serum levels of both Fuc-Hpt and Mac-2 bp increased with the progression of liver fibrosis. The multivariate analysis revealed that Mac-2 bp was an independent factor associated with moderate liver fibrosis (F ≥ 2). In contrast, Fuc-Hpt was an independent factor associated with advanced liver fibrosis (F ≥ 3). In terms of evaluating liver fibrosis, the serum levels of these glycomarkers were correlated with well-known liver fibrosis indexes, such as the aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB4) index. An assay that combined the APRI or FIB4 index and the Fuc-Hpt or Mac-2 bp levels increased the AUC value for diagnosing hepatic fibrosis. Interestingly, the cumulative incidence of hepatocellular carcinoma (HCC) was significantly higher in the patients with elevated serum levels of Fuc-Hpt and Mac-2 bp. In conclusion, both Fuc-Hpt and Mac-2 bp could be useful glyco-biomarkers of liver fibrosis and predictors of HCC in patients with chronic hepatitis C.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Tawara
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.affiliation: Department of Gastroenterological Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan.
authors.forename: Sadaharu
authors.initials: S
authors.lastname: Iio
authors.affiliation: Department of Gastroenterological Medicine, Higashiosaka City General Hospital, Higashiosaka, Osaka, Japan.
authors.forename: Ichizou
authors.initials: I
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Shigekawa
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Hikita
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Sakamori
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000453:epidemiology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006242:Haptoglobins / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000473:pathology* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D008113:Liver Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D006242:Haptoglobins; D008562:Membrane Glycoproteins; C114782:TAA90K protein, human