Peripheral CXCR3-associated chemokines as biomarkers of fibrosis in chronic hepatitis C virus infection.
BACKGROUND
CXCR3-associated chemokines CXCL9-CXCL11 promote histologic progression in chronic hepatitis C virus (HCV) infection, as indicated by elevated intrahepatic levels of messenger RNA in patients with advanced inflammation and fibrosis. We evaluated the potential of peripheral chemokine levels to discriminate among patients with chronic HCV infection who had different stages of fibrosis.


METHODS
Peripheral levels of CXCR3-associated chemokines were measured by enzyme-linked immunosorbent assay of plasma samples obtained from 93 patients with chronic HCV infection. Of the subjects, 79 (85%) were white, and 68 (73%) were infected with HCV genotype 1.


RESULTS
Expression of all 3 chemokines, when analyzed as a group, was significantly associated with intrahepatic inflammation and fibrosis. Plasma levels of CXCL10 were significantly elevated in patients with advanced fibrosis, whereas CXCL9 levels were significantly elevated in patients with advanced inflammation. By proportional odds multivariate modeling, we observed an association between fibrosis and CXCL10 (P< .002) as well as between fibrosis and inflammation (P<.001). Of the individual parameters, the CXCL10 level was most useful in identifying patients with more-severe (stage 3-4) fibrosis. Discriminatory ability was improved by the combination of CXCL10 and CXCL9.


CONCLUSIONS
The strong association between CXCR3-associated chemokines and fibrosis suggests that they may have promise as noninvasive markers of hepatic fibrosis in a predominantly white HCV genotype 1-infected population.
Division of Gastroenterology and Hepatology and Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, USA.
Marija
M
Zeremski
Rositsa
R
Dimova
Queenie
Q
Brown
Ira M
IM
Jacobson
Marianthi
M
Markatou
Andrew H
AH
Talal
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood*; D054370:Chemokine CXCL9 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012372:ROC Curve; D054367:Receptors, CXCR3 / Q000097:blood*
D015415:Biomarkers; C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D054367:Receptors, CXCR3