Elevated serum type IV collagen: a sensitive indicator of the presence of cirrhosis in haemochromatosis

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Abstract

Background/Aim: 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.

Section snippets

Patients

Forty-two patients with haemochromatosis were studied in this study. The diagnosis of haemochromatosis was made by established clinical and biochemical criteria 1., 2. and confirmed by histological and biochemical assessment of liver biopsy specimens. The hepatic iron index (HII) was >2.0 in 40 of the 42 patients. One patient did not have a hepatic iron concentration (HIC) measurement but had grade 4 iron deposition on Perls' stain and was HLA identical to a sibling with established

Histology

Histological evaluation of liver biopsies showed eight patients had no fibrosis (grade 0), whereas eight, 16 and five patients had grade 1, 2 and 3 fibrosis, respectively. Five patients had cirrhosis (grade 4). Fourteen patients had mild (grade 1) acinar or portal inflammation.

Serum laminin

There was no significant difference between the mean serum laminin concentration of control subjects and patients with haemochromatosis (251±112 ng/ml vs 237±143 ng/ml). Within the group of haemochromatosis patients there

Discussion

These results demonstrate that an elevated serum type IV collagen concentration is a sensitive indicator of severe fibrosis or cirrhosis in patients with hereditary haemochromatosis and can be used in clinical decision making as to whether liver biopsy is indicated in patients identified as having homozygous haemochromatosis by genetic testing. The results of this study also demonstrate that serum fibrosis markers shown to be useful in other chronic liver diseases do not necessarily extrapolate

Acknowledgements

This study was funded by a grant from the National Health and Medical Research Council of Australia (GAR, LWP, DHGC). Dr. George was supported by a Bancroft Scholarship from The Queensland Institute of Medical Research and a Wellcome Travel Scholarship.

Portions of this work have been presented at the annual meeting of the European Association for the Study of Liver and have been published in abstract form (J Hepatol 1998; 28(Suppl): A142).

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