Hepcidin and the iron enigma in HCV infection

Abstract

An estimated 30-40% of patients with chronic hepatitis C have elevated serum iron, transferrin saturation, and ferritin levels. Clinical data suggest that iron is a co-morbidity factor for disease progression following HCV infection. Iron is essential for a number of fundamental metabolic processes in cells and organisms. Mammalian iron homeostasis is tightly regulated and this is maintained through the coordinated action of sensory and regulatory networks that modulate the expression of iron-related proteins at the transcriptional and/or posttranscriptional levels. Disturbances of iron homeostasis have been implicated in infectious disease pathogenesis. Viruses, similarly to other pathogens, can escape recognition by the immune system, but they need iron from their host to grow and spread. Hepcidin is a 25-aa peptide, present in human serum and urine and represents the key peptide hormone, which modulates iron homeostasis in the body. It is synthesized predominantly by hepatocytes and its mature form is released in circulation. In this review, we discuss recent advances in the exciting crosstalk of molecular mechanisms and cell signaling pathways by which iron and hepcidin production influences HCV-induced liver disease.

Keywords: cell signaling pathways; hepatitis C virus; hepcidin; iron; lipid metabolism.

Figure 1. Hepcidin is primarily synthesized in hepatocytes and then released into the circulation. When hepcidin reaches circulation, it regulates iron metabolism by controlling iron transport to duodenal enterocytes and iron export from macrophages.

Figure 2. Schematic illustration of the crosstalk between the three main cell signaling pathways involved in the regulation of hepcidin and their modulation by HCV structural and non-structural proteins.