Chondrex (YKL-40), a potential new serum fibrosis marker in patients with alcoholic liver disease.

OBJECTIVES: Chondrex (YKL-40) is a mammalian member of a protein family that includes bacterial chitinases. The pattern of its expression in certain tissues such as human liver or cartilage suggests a function in remodelling or degradation of extracellular matrix. The purpose of this study was to assess whether circulating YKL-40 might be a serum fibrosis marker in alcoholics. METHODS: Plasma YKL-40 was determined in 146 consecutive heavy drinkers (106 men, 40 women; mean age, 49.2 +/- 9.0 years). Liver biochemical parameters and serum fibrosis markers such as hyaluronate were also measured. Fibrosis and inflammation in liver biopsy were evaluated using a semi-quantitative scoring system. RESULTS: Plasma YKL-40 increased in parallel with the severity of fibrosis (P<0.00001). YKL-40 also increased in the presence of hepatic inflammation (P<0.01). Receiver operating characteristic curves of Chondrex revealed that a threshold of 330 microg/l gave a specificity of 88.5%; however, the sensitivity was only 50.8%. Only 11.5% of patients without severe fibrosis displayed a Chondrex plasma level above this threshold. A positive correlation was found between Chondrex and hyaluronate (r=0.40, P<0.0001), and a negative correlation was shown between Chondrex and the prothrombin index (r=-0.37, P<0.0001). CONCLUSIONS: The severity of liver fibrosis is associated with elevated circulating Chondrex levels. The overlap in YKL-40 values prevents use of Chondrex in a screening programme. High levels of Chondrex (above 330 microg/l) are predictive of severe liver fibrosis. Increased plasma YKL-40 may reflect the remodelling of liver fibrosis in alcoholics.

Non invasive prediction of severe fibrosis in patients with alcoholic liver disease.

OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of noninvasive markers of liver fibrosis in alcoholic liver disease. PATIENTS AND METHODS: Fifty-four clinical and biochemical parameters including serum fibrosis markers (hyaluronate and transforming growth factor beta1) were analyzed in 146 consecutive heavy drinkers (106 men, 40 women; mean age 49.2 years). Following liver biopsy, fibrosis was evaluated using a semi-quantitative scoring system (no fibrosis (0) to severe fibrosis (3 + )). Multivariate analysis was performed to determine the markers that were best correlated with the fibrosis score. RESULTS: Fifty-nine patients (40.4 %) had severe fibrosis (3 +) while 87 (59.6 %) had no fibrosis or moderate fibrosis (0 to 2 +). In multivariate analysis, serum hyaluronate and the prothrombin index were the best markers for the prediction of severe fibrosis. Hyaluronate and the prothrombin index had a diagnostic accuracy of 91.1 % and 89.7 %, respectively in the whole population. Finally, a significant negative correlation was found between hyaluronate and the prothrombin index (r =- 0.86, P <0.0001). CONCLUSIONS: Using only hyaluronate and the prothrombin index, 9 out of 10 alcoholic patients can be correctly classified according to the severity of liver fibrosis.