PLASMA YKL-40 - A NEW POTENTIAL MARKER OF FIBROSIS IN PATIENTS WITH ALCOHOLIC CIRRHOSIS

Background: YKL-40 (human cartilage glycoprotein-39, or 38-kDa heparin -binding glycoprotein) is a mammalian member of a protein family that includes bacterial chitinases. YKL-40 mRNA is expressed by human liver and may play a role in tissue remodelling. The aims were to assess wh ether circulating YKL-40 is released or extracted in the hepatosplanch nic system and to localize YKL-40 in liver tissue. Methods: Plasma YKL -40 was determined by radioimmunoassay in 25 patients with liver disea ses (alcoholic cirrhosis (n = 20), chronic active hepatitis (n = 2), c irrhosis of unknown aetiology (n = 2), and fatty liver (n = 1)) and in 18 subjects with normal liver function during a haemodynamic investig ation with catheterization of liver vein and the femoral artery. Immun ohistochemical studies of the localization of YKL-40 in cryostat liver biopsy specimens were obtained from eight other patients with alcohol ic liver disease. Results: Plasma YKL-40 was significantly increased i n patients with alcoholic cirrhosis (median, 523 mu g/l; P < 0.001) co mpared with controls (106 mu g/l), and plasma YKL-40 in the hepatic ve in was higher (P < 0.01) than that of the artery in both the patients and controls, showing release of YKL-40 from the hepatosplanchnic area . The release rate of YKL-40 from the hepatosplanchnic area was higher in patients with liver disease than in controls (11.0 versus 2.1 mu g /min, P < 0.05). Furthermore, the highest plasma YKL-40 levels were fo und in patients with a moderate or severe degree of liver fibrosis, an d immunohistochemical studies showed positive staining for YKL-40 anti gen in areas of the liver biopsy with fibrosis. Conclusions: The incre ased plasma YKL-40 in patients with alcoholic cirrhosis may reflect th e remodelling of liver fibrosis.