title: Serum hyaluronan--a non-invasive test for diagnosing liver cirrhosis.
abstract: BACKGROUND
  Hyaluronan is a glucosaminoglycan synthesized by the mesenchymal cells and degraded by hepatic sinusoidal endothelial cells by a specific receptor-mediated process. Elevated levels are associated with the sinusoidal capillarization that is seen in cirrhosis.
  
  
  METHODS
  Serum hyaluronan was measured, using a radiometric assay (Pharmacia, Sweden) in 221 patients with biopsy-proven chronic liver disease of a variety of aetiologies (alcohol n = 70, autoimmune chronic active hepatitis n = 23, primary biliary cirrhosis n = 17, hepatitis C n = 69, cryptogenic n = 15, various n = 27). All patients were fasted, and their liver function tests, full blood count, prothrombin time and Child-Pugh score were assessed at the time of the liver biopsy.
  
  
  RESULTS
  Hyaluronan levels (microg/l) were significantly higher in patients with liver cirrhosis (cirrhosis n = 127, mean 440, 95% CI 367-515) (P < 0.0001) compared with hepatic fibrosis (n = 23, mean 144, 95% CI 69-190), chronic hepatitis (n = 60, mean 63, 95% CI 37-91) and fatty liver (n = 11, mean 107, 95% CI 37-177). Within the cirrhotic population, there was no significant difference in hyaluronan levels between different aetiologies, but hyaluronan level increased proportionally to the severity of cirrhosis. Overall, a hyaluronan level > 100 microg/l had a 78% specificity and 83% sensitivity for diagnosing cirrhosis, while the specificity was increased to 96% for all patients with hyaluronan levels > 300 microg/l. The highest specificity and sensitivity were seen at a cut-off value of 100 microg/l in patients with alcohol-associated liver disease (89%, 87%) and hepatitis C (93%, 72%) respectively. Within patient cohorts, there was a significant correlation (P < 0.01) between hyaluronan and albumin, platelet count and bilirubin, but not with alanine aminotransferase.
  
  
  CONCLUSIONS
  Measurement of fasted serum hyaluronan reliably differentiated cirrhotic from non-cirrhotic liver disease and can be regarded as a useful test in the diagnosis of liver cirrhosis, particularly when a liver biopsy is contraindicated.
authors.affiliation: University Department of Internal Medicine, The Royal Infirmary, University of Edinburgh, UK. J.Plevris@ed.ac.uk
authors.forename: J N
authors.initials: JN
authors.lastname: Plevris
authors.forename: G H
authors.initials: GH
authors.lastname: Haydon
authors.forename: K J
authors.initials: KJ
authors.lastname: Simpson
authors.forename: R
authors.initials: R
authors.lastname: Dawkes
authors.forename: C A
authors.initials: CA
authors.lastname: Ludlum
authors.forename: D J
authors.initials: DJ
authors.lastname: Harrison
authors.forename: P C
authors.initials: PC
authors.lastname: Hayes
mesh_terms: D001706:Biopsy; D003362:Cost-Benefit Analysis; D005234:Fatty Liver / Q000097:blood; D006025:Glycosaminoglycans / Q000097:blood; D019698:Hepatitis C, Chronic / Q000097:blood; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis* / Q000191:economics; D016015:Logistic Models; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000191:economics / Q000379:methods; D012720:Severity of Illness Index
chemical_list: D006025:Glycosaminoglycans; C020341:glucosaminoglycans; D006820:Hyaluronic Acid