Review
Copyright ©2010 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Hepatol. Aug 27, 2010; 2(8): 302-310
Published online Aug 27, 2010. doi: 10.4254/wjh.v2.i8.302
Gender-related variations in iron metabolism and liver diseases
Duygu D Harrison-Findik
Duygu D Harrison-Findik, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5820, United States
Author contributions: Harrison-Findik DD wrote solely the paper.
Supported by the NIH Grant (R01AA017738) to Duygu Dee Harrison-Findik
Correspondence to: Duygu Dee Harrison-Findik, PhD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, 95820 UNMC Omaha, NE 68198-5820, United States. dharrisonfindik@unmc.edu
Telephone: +1-402-5596355 Fax: +1-402-5596494
Received: May 17, 2010
Revised: June 30, 2010
Accepted: July 7, 2010
Published online: August 27, 2010
Abstract

The regulation of iron metabolism involves multiple organs including the duodenum, liver and bone marrow. The recent discoveries of novel iron-regulatory proteins have brought the liver to the forefront of iron homeostasis. The iron overload disorder, genetic hemochromatosis, is one of the most prevalent genetic diseases in individuals of Caucasian origin. Furthermore, patients with non-hemochromatotic liver diseases, such as alcoholic liver disease, chronic hepatitis C or nonalcoholic steatohepatitis, often exhibit elevated serum iron indices (ferritin, transferrin saturation) and mild to moderate hepatic iron overload. Clinical data indicate significant differences between men and women regarding liver injury in patients with alcoholic liver disease, chronic hepatitis C or nonalcoholic steatohepatitis. The penetrance of genetic hemochromatosis also varies between men and women. Hepcidin has been suggested to act as a modifier gene in genetic hemochromatosis. Hepcidin is a circulatory antimicrobial peptide synthesized by the liver. It plays a pivotal role in the regulation of iron homeostasis. Hepcidin has been shown to be regulated by iron, inflammation, oxidative stress, hypoxia, alcohol, hepatitis C and obesity. Sex and genetic background have also been shown to modulate hepcidin expression in mice. The role of gender in the regulation of human hepcidin gene expression in the liver is unknown. However, hepcidin may play a role in gender-based differences in iron metabolism and liver diseases. Better understanding of the mechanisms associated with gender-related differences in iron metabolism and chronic liver diseases may enable the development of new treatment strategies.

Keywords: Alcohol; Hepcidin; Hepatitis C; Hemochromatosis; Non-alcoholic steatohepatitis