Chondrex (YKL-40), a potential new serum fibrosis marker in patients with alcoholic liver disease.
OBJECTIVE
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.
Tran
A
A
Liver Unit, Archet 2 Hospital, Nice, France. tran@unice.fr
Benzaken
S
S
Saint-Paul
M C
MC
Guzman-Granier
E
E
Hastier
P
P
Pradier
C
C
Barjoan
E M
EM
Demuth
N
N
Longo
F
F
Rampal
P
P
D054392:Adipokines; D001324:Autoantigens / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D037102:Lectins; D008099:Liver / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood* / Q000145:classification / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012720:Severity of Illness Index
D054392:Adipokines; D001324:Autoantigens; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins