Iron metabolic disorder in chronic hepatitis C: insights from recent evidence

The liver is the major iron storage organ in the body, and therefore iron metabolic disorder is sometimes involved in chronic liver diseases. Chronic hepatitis C is one of the liver diseases that show hepatic iron accumulation. The present review highlights the current concept of hepatic iron overload status in chronic hepatitis C and discusses how iron metabolic disorder develops in this disease, and the impact of hepatic iron overload on disease progression and its relevance to hepatocarcinogenesis. The level of hepatic iron accumulation in chronic hepatitis C should be recognized to be basically mild to moderate and sometimes within the normal range. However, even mild to moderate iron overload in the liver contributes to disease progression and hepatocarcinogenesis in chronic hepatitis C, probably by reinforcing the oxidative stress induced by hepatitis C virus (HCV) protein. The mechanisms by which hepatic iron overload develops in chronic hepatitis C have not been fully elucidated. Reduction of the transcription activity of hepcidin by HCV-induced reactive oxygen species may in part account for it, but the regulation of hepcidin is very complex and may depend on many variables, including the particular stage of the systemic and/or hepatic inflammatory conditions and the circulating transferrin-bound iron and intracellular iron stores. This might explain the variations in hepatic iron concentrations reported among patients with HCV-related chronic liver disease.