Iron, hemochromatosis, and hepatocellular carcinoma.
Hereditary hemochromatosis (HH) is associated with an increased risk for hepatocellular carcinoma (HCC). The risk previously had been estimated to be as high as 200-fold increased. Recent studies suggest that the risk for HCC in HFE -associated HH may be much lower and occurs predominantly in patients with cirrhosis at the time of diagnosis. The risk for HCC also is increased among patients with African iron overload and possibly in other iron-loading disorders such as homozygous beta thalassemia. The greatly increased iron stores in the liver observed in these disorders can stimulate carcinogenesis via both direct and indirect pathways. The prevalence of HCC also appears to be higher among patients with end-stage liver disease undergoing liver transplantation. It is not clear whether mildly to moderately increased hepatic iron stores or HFE mutations are associated independently with an increased risk for HCC among patients with other types of liver disease. In this article, the incidence and prevalence of HCC in patients with HH and other liver diseases associated with iron overload are discussed as well as the possible mechanisms for the increased risk for hepatic carcinogenesis in these disorders.
Kowdley
Kris V
KV
University of Washington, Box 356174, 1959 NE Pacific Street, Seattle, Washington 98195, USA. kkowdley@u.washington.edu
D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000503:physiopathology*; D049109:Cell Proliferation; D006432:Hemochromatosis / Q000150:complications*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D015994:Incidence; D007501:Iron / Q000009:adverse effects* / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic; D008113:Liver Neoplasms / Q000453:epidemiology / Q000503:physiopathology*; D008565:Membrane Proteins / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron