Introduction

The liver synthesizes transferrin and ferritin, and is the major tissue storage site of iron. Consequently, iron metabolism may be altered in chronic hepatitis. Stored ferritin may be released into the circulation due to lysis of damaged hepatocytes, leading to elevated serum ferritin concentrations. Transferrin receptor expression by hepatocytes may be up-regulated as a consequence of chronic inflammation, and lead to increased iron absorption and hepatic iron. Chronic viral hepatitis may up-regulate hepatic production of transferrin receptor or ferritin directly and effect increased hepatic iron deposition. Thus, chronic inflammatory processes in the liver such as viral hepatitis may cause increased plasma and hepatic iron concentrations by a variety of mechanisms. Ferrous iron promotes free radical formation and lipid peroxidation that mediates acute and chronic tissue damage. Because iron status influences the immune response, primary iron overload disorders and hepatic iron overload have been linked to an increased risk of bacterial infections due to Vibrio, Neisseria, and Yersinia. Iron may act as a substrate for viral replication, and therefore patients with chronic viral hepatitis and iron overload may have increased viral replication. The iron-binding proteins lactoferrin and transferrin play an important role in the immune response to infection. Although the effect of lactoferrin on hepatitis C virus replication is unknown, lactoferrin inhibits replication of herpes simplex virus, cytomegalovirus, and human immunodeficiency virus in vitro. Therefore, iron status in patients with chronic viral hepatitis may be important clinically due to its effects on hepatic inflammation and viral replication, and reducing iron stores may decrease hepatic injury in patients with chronic hepatitis.