Serum markers of hepatic fibrogenesis in cystic fibrosis liver disease.
OBJECTIVE
Hepatic fibrosis contributes to adverse outcome in cystic fibrosis (CF). Early detection of CF liver disease (CFLD) may identify patients at risk of significant complications. To evaluate the utility of serum markers to detect hepatic fibrosis in children with CFLD vs. CF patients without liver disease (CFnoLD) and controls.


METHODS
Sera from 36 CFLD, 30 CFnoLD and 39 controls were assessed for tissue inhibitor of matrix metalloproteinase (MMP) (TIMP)-1, collagen (CL)-IV, MMP-2, hyaluronic acid (HA) and prolyl hydroxylase (PH) by enzyme immunoassay and were correlated with hepatic fibrosis score in CFLD.


RESULTS
TIMP-1, PH and CL-IV were increased in CFLD vs. CFnoLD and controls. Fibrosis score was negatively correlated with TIMP-1 (r=-0.34, P=0.06) and PH (r=-0.48, P=0.008). Receiver-operating characteristics analysis showed CL-IV (AUC 0.785, P<0.0001) and TIMP-1 (AUC 0.765, P<0.0001) differentiated CFLD from CFnoLD and controls, while PH (AUC 0.814, P<0.0001) predicted early fibrogenesis. Diagnostic accuracy improved using logistic regression combining (i) CL-IV, TIMP-1, PH to identify CFLD (AUC 0.831, P<0.0001) and (ii) TIMP-1, PH to identify CFLD patients with no fibrosis (AUC 0.852, P<0.02).


CONCLUSIONS
Elevated TIMP-1, CL-IV, PH may be indicators of hepatic fibrogenesis in CF. Increased TIMP-1, PH may be early markers of CFLD.
The Hepatic Fibrosis Group, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Qld 4029, Australia.
Tamara N
TN
Pereira
Peter J
PJ
Lewindon
Jeffery L
JL
Smith
Therese L
TL
Murphy
Douglas J
DJ
Lincoln
Ross W
RW
Shepherd
Grant A
GA
Ramm
D000293:Adolescent; D000375:Aging / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000097:blood; D003550:Cystic Fibrosis / Q000097:blood / Q000150:complications*; D005260:Female; D006801:Humans; D007223:Infant; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D011393:Procollagen-Proline Dioxygenase / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D015415:Biomarkers; D024141:Collagen Type IV; D019715:Tissue Inhibitor of Metalloproteinase-1; D011393:Procollagen-Proline Dioxygenase