Serum hyaluronan--a non-invasive test for diagnosing liver cirrhosis.
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.
Plevris
J N
JN
University Department of Internal Medicine, The Royal Infirmary, University of Edinburgh, UK. J.Plevris@ed.ac.uk
Haydon
G H
GH
Simpson
K J
KJ
Dawkes
R
R
Ludlum
C A
CA
Harrison
D J
DJ
Hayes
P C
PC
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
D006025:Glycosaminoglycans; C020341:glucosaminoglycans; D006820:Hyaluronic Acid