title: Hyaluronic acid as a non-invasive biomarker of liver fibrosis.
abstract: Chronic liver diseases may cause inflammation and progressive scarring, over time leading to irreversible hepatic damage (cirrhosis). As a result, the need to assess and closely monitor individuals for risk factors of components of matrix deposition and degradation, as well as the severity of the fibrosis using biomarkers, has been increasingly recognized.
  
  
  OBJECTIVE
  Our aim is to review the use of biomarker for diagnosing and defining the severity of liver fibrosis.
  
  
  METHODS
  A systematic literature review was done using the terms "hyaluronic acid" and "liver fibrosis" as well as the name of each biomarker or algorithm known to be employed. PubMed and Google Scholar were searched, and English language articles indexed between January 2010 and October 2014 in which HA was used as a marker of liver fibrosis were retrieved, regardless of the underlying liver disease. Each author read the publications separately and the results were analyzed and discussed.
  
  
  RESULTS
  Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression, or both. Serum biomarkers, including HA, have been used for many years. Emerging biomarkers such as metalloproteinases have been proposed as tools that provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of extracellular matrix degradation provide powerful predictions of risk. In order for biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in gender and ethnic origin are a necessity.
  
  
  CONCLUSIONS
  This review attempts to provide a comprehensive analysis of the emerging risk biomarkers of liver fibrosis and to describe the clinical significance and analytical considerations of each biomarker pointing out sentinel features of disease progression.
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, CEO In Vitro Drug Safety & BioTechnology, Banting Institute, 100 College Street, Lab 217, Toronto, Ontario M5G 0A3, Canada.
authors.forename: Manuela G
authors.initials: MG
authors.lastname: Neuman
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, CEO In Vitro Drug Safety & BioTechnology, Banting Institute, 100 College Street, Lab 217, Toronto, Ontario M5G 0A3, Canada; Sunnybrook HSC, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Cohen
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, CEO In Vitro Drug Safety & BioTechnology, Banting Institute, 100 College Street, Lab 217, Toronto, Ontario M5G 0A3, Canada.
authors.forename: Radu M
authors.initials: RM
authors.lastname: Nanau
mesh_terms: D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D019698:Hepatitis C, Chronic / Q000097:blood; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis*; D011379:Prognosis; D012016:Reference Values; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D006820:Hyaluronic Acid
keywords: Fibrosis; Histological activity index; Hyaluronic acid; Liver biopsy; Non-invasive biomarkers