Body Iron and Chronic Liver Diseases

As a target organ, the liver is particularly susceptible to excess iron levels. Hepatic iron overload induces mitochondrial injury and DNA mutagenesis, being an independent factor associated with hepatic fibrosis along with cell death, and increasing the risk of hepatocellular carcinoma development. In humans with iron overload due to either genetic or acquired causes, fibrosis and cirrhosis are hallmarks of liver disease. The clinical expression of genetic hemochromatosis is 5 to 10 times more frequent in men than in women, especially because of iron losses in women by menstruation and pregnancy. Iron deficiency is prevalent in females of reproductive age. Iron deficiency anemia is more commonly found in females than males. Women, especially before menopause, have lower iron stores in the liver. Hepcidin is a circulatory peptide synthesized in the liver that appears to regulate iron absorption in the duodenum. It is noteworthy that female mice express higher hepcidin levels in the liver than males, although it is not known whether women and men differ in the level of hepatic hepcidin expression. Sex-related differences in body iron storage and metabolism may be a potential candidate to explain in part the observed sex-related differences in many chronic liver diseases.

Keywords: Hepatic iron, iron overload, mitochondrial injury, hepatic fibrosis, oxidative stress, DNA mutagenesis, cell death, hemochromatosis, menstruation, pregnancy, iron deficiency anemia, hepcidin