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World J Gastroenterol. Sep 21, 2007; 13(35): 4673-4689
Published online Sep 21, 2007. doi: 10.3748/wjg.v13.i35.4673
HFE gene in primary and secondary hepatic iron overload
Giada Sebastiani, Ann P Walker
Giada Sebastiani, Venetian Institute of Molecular Medicine (VIMM), Padova and Digestive Diseases, Hepatology and Clinical Nutrition Department, Umberto I Hospital, Venice, Italy
Ann P Walker, Department of Medicine, University College London, London, United Kingdom
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Giada Sebastiani, Venetian Institute of Molecular Medicine (VIMM), Padova and Digestive Diseases, Hepatology and Clinical Nutrition Department, Umberto I Hospital, Venice, Italy. giagioseba@iol.it
Telephone: +39-49-8212293 Fax: +39-49-8211826
Received: March 30, 2007
Revised: May 1, 2007
Accepted: May 9, 2007
Published online: September 21, 2007
Abstract

Distinct from hereditary haemochromatosis, hepatic iron overload is a common finding in several chronic liver diseases. Many studies have investigated the prevalence, distribution and possible contributory role of excess hepatic iron in non-haemochromatotic chronic liver diseases. Indeed, some authors have proposed iron removal in liver diseases other than hereditary haemochromatosis. However, the pathogenesis of secondary iron overload remains unclear. The High Fe (HFE) gene has been implicated, but the reported data are controversial. In this article, we summarise current concepts regarding the cellular role of the HFE protein in iron homeostasis. We review the current status of the literature regarding the prevalence, hepatic distribution and possible therapeutic implications of iron overload in chronic hepatitis C, hepatitis B, alcoholic and non-alcoholic fatty liver diseases and porphyria cutanea tarda. We discuss the evidence regarding the role of HFE gene mutations in these liver diseases. Finally, we summarize the common and specific features of iron overload in liver diseases other than haemochromatosis.

Keywords: Hereditary haemochromatosis; Chronic liver diseases; Chronic hepatitis C; Hepatic iron overload; HFE gene