Elevated serum type IV collagen: a sensitive indicator of the presence of cirrhosis in haemochromatosis.
OBJECTIVE
Hereditary haemochromatosis can now be diagnosed by genetic testing, although determining the presence or absence of cirrhosis remains crucial to patient management. While many studies have investigated the utility of various serum markers of cirrhosis in chronic liver diseases, few have examined specifically patients with hereditary haemochromatosis. The aim of this study was to assess the utility of serum type IV collagen and serum laminin in diagnosing hepatic fibrosis and cirrhosis in patients with hereditary haemochromatosis.


METHODS
The study group consisted of 42 patients with hereditary haemochromatosis and 19 Caucasian controls. Serum type IV collagen, laminin, matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-1) concentrations were measured by enzyme-linked immunosorbant assay in serum from patients with haemochromatosis and control subjects. Liver biopsies from patients with haemochromatosis were graded for fibrosis and correlated with serum markers of hepatic fibrosis.


RESULTS
Serum type IV collagen concentration was significantly increased in haemochromatosis patients compared to controls (130+/-79 ng/ml vs 81 +/- 17 ng/ml, p<0.05) and was significantly correlated with both the grade of histological fibrosis (r=0.67, p<0.0001) and serum MMP-2 levels (r=0.42, p<0.05). A serum type IV collagen concentration > 115 ng/ml (mean+2 SD of controls) was 100% sensitive and 69% specific in detecting severe (grade 3) fibrosis and cirrhosis. The sensitivity results of serum laminin and TIMP-1 were 11% and 56% respectively.


CONCLUSIONS
Elevated serum type IV collagen is a sensitive indicator of the presence of severe fibrosis and cirrhosis in patients with haemochromatosis. Useful markers of hepatic fibrosis in other chronic liver diseases may not be applicable to haemochromatosis.
George
D K
DK
Joint Clinical Sciences Program, University of Queensland Department of Medicine and Queensland Institute of Medical Research, Brisbane, Australia.
Ramm
G A
GA
Walker
N I
NI
Powell
L W
LW
Crawford
D H
DH
D015415:Biomarkers / Q000097:blood; D003094:Collagen / Q000097:blood*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D018093:Gelatinases / Q000097:blood; D006432:Hemochromatosis / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism; D007797:Laminin / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000097:blood; D011237:Predictive Value of Tests; D012016:Reference Values; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D044465:White People
D015415:Biomarkers; D007797:Laminin; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D007501:Iron; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2