title: A secreted form of the asialoglycoprotein receptor, sH2a, as a novel potential noninvasive marker for liver fibrosis.
abstract: OBJECTIVE
  The human asialoglycoprotein receptor is a membrane heterooligomer expressed exclusively in hepatocytes. A soluble secreted form, sH2a, arises, not by shedding at the cell surface, but by intracellular cleavage of its membrane-bound precursor, which is encoded by an alternatively spliced form of the receptor H2 subunit. Here we determined and report that sH2a, present at constant levels in serum from healthy individuals is altered upon liver fibrosis, reflecting the status of hepatocyte function.
  
  
  METHODS
  We measured sH2a levels in serum using a monoclonal antibody and an ELISA assay that we developed, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of 44 hepatitis C patients, which had METAVIR-scored biopsies, with 28 healthy individuals.
  
  
  RESULTS
  sH2a levels varied minimally for the healthy individuals (150±21 ng/ml), whereas the levels deviated from this normal range increasingly in correlation with fibrosis stage. A simple algorithm combining sH2a levels with those of alanine aminotransferase allowed prediction of fibrosis stage, with a very high area under the ROC curve of 0.86.
  
  
  CONCLUSIONS
  sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function.
authors.affiliation: Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Veselkin
authors.forename: Maria
authors.initials: M
authors.lastname: Kondratyev
authors.forename: Yoav
authors.initials: Y
authors.lastname: Lurie
authors.forename: Efrat
authors.initials: E
authors.lastname: Ron
authors.forename: Moshe
authors.initials: M
authors.lastname: Santo
authors.forename: Shimon
authors.initials: S
authors.lastname: Reif
authors.forename: Irma
authors.initials: I
authors.lastname: Elashvili
authors.forename: Lana
authors.initials: L
authors.lastname: Bar
authors.forename: Gerardo Z
authors.initials: GZ
authors.lastname: Lederkremer
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D037263:Asialoglycoprotein Receptor / Q000097:blood* / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D001663:Bilirubin / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016001:Confidence Intervals; D005260:Female; D006526:Hepatitis C / Q000097:blood / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D037263:Asialoglycoprotein Receptor; D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin
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