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Steatohepatitis/Metabolic Liver Disease
Article first published online: 19 JUN 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 3, pages 904–911, September 2012
How to Cite
Wood, M. J., Powell, L. W., Dixon, J. L. and Ramm, G. A. (2012), Clinical cofactors and hepatic fibrosis in hereditary hemochromatosis: The role of diabetes mellitus. Hepatology, 56: 904–911. doi: 10.1002/hep.25720
Potential conflict of interest: Nothing to report.
M.J.W. is supported by a National Health and Medical Research Council (NHMRC) Medical Postgraduate Scholarship and the Royal Brisbane and Women's Hospital Research Foundation. G.A.R. and L.W.P. are supported by the NHMRC. This work was supported, in part, by a kind donation from the Hemochromatosis Society of Australia. G.A.R. is also supported by a NHMRC Senior Research Fellowship (#552409).
- Issue published online: 28 AUG 2012
- Article first published online: 19 JUN 2012
- Accepted manuscript online: 15 MAR 2012 07:27AM EST
- Manuscript Accepted: 1 MAR 2012
- Manuscript Received: 21 DEC 2011
The risk of hepatic fibrosis and cirrhosis in hereditary hemochromatosis relates to the degree of iron loading, but iron alone does not explain the variability in disease penetrance. This study sought to identify clinical cofactors that increase the risk of progressive liver disease. We identified 291 patients from our database who were homozygous for the C282Y mutation in HFE and had undergone a liver biopsy with quantification of hepatic iron concentration (HIC) and fibrosis staging. Data were collected from a retrospective chart review, including age, gender, alcohol consumption, medical therapy, smoking history, metabolic risk factors, mobilizable iron, and laboratory results. Male gender, excess alcohol consumption, HIC, and the presence of diabetes were independently associated with increasing fibrosis stage in multivariate analysis. Of these, the presence of diabetes showed the strongest association (odds ratio, 7.32; P = 0.03). The presence of steatosis was associated with higher fibrosis scores, but this was of borderline statistical significance. Risk factors for hepatic steatosis were male gender, impaired glucose tolerance, and increased body mass index. Conclusion: The presence of diabetes was associated with more severe hepatic fibrosis independent of iron loading, male gender, and alcohol consumption. The mechanism for this association is unknown and deserves further evaluation; however, it is possible that diabetes produces an additional hepatic oxidative injury from hyperglycemia. Thus, management of such cofactors in patients with hemochromatosis is important to reduce the risk of liver injury and fibrosis. (Hepatology 2012;56:904–911)