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Serum hyaluronan--a non-invasive test for diagnosing liver cirrhosis
J N Plevris1, G H Haydon, K J Simpson
1University Department of Internal Medicine, The Royal Infirmary, University of Edinburgh, UK. J.Plevris@ed.ac.uk
Introduction:
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.
Methodology:
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.
Conclusion:
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.