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Increased hepatic iron content may be observed in patients with chronic hepatitis C infection, and may contribute to disease severity. The presence of hemochromatosis gene mutations is associated with increased hepatic iron accumulation and may lead to accelerated disease progression. Hepatic iron depletion has been postulated to decrease the risk of hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C. It is possible that iron depletion stabilizes or improves liver histology and slows disease progression in these individuals. The present article reviews the prevalence and risk factors for hepatic iron overload in chronic hepatitis C, with emphasis on the available data regarding the efficacy of iron depletion in the treatment of this common liver disease.