Hepatic iron overload and hepatocellular carcinoma

Abstract

In recent years it has become increasingly evident that excess body iron may be complicated by the supervention of hepatocellular carcinoma (HCC). Hereditary hemochromatosis (HH) was the first condition in which hepatic iron overload was shown to predispose to the development of HCC. The inherited predisposition to excessive absorption of dietary iron in HH is almost always the result of homozygosity of the C282Y mutation of the HFE gene, which causes inappropriately low secretion of hepcidin. HCC develops in 8-10% of patients with HH and is responsible for approximately 45% of deaths in the HCC patients. Cirrhosis is almost always present when HCC is diagnosed. Dietary iron overload is a condition which occurs in rural-dwelling Black Africans in southern Africa as a result of the consumption, over time, of large volumes of alcohol home-brewed in iron containers and having, as a consequence, a high iron content. Iron loading of the liver results and may be complicated by malignant transformation of the liver (relative risk of approximately 10.0). Accompanying cirrhosis does occur but is less common than that in HH. The development of HCC as a consequence of increased dietary iron, and the fact that it may develop in the absence of cirrhosis, has been confirmed in an animal model. Drinking water with a high iron content might contribute to the high incidence of HCC in parts of Taiwan. The metabolic syndrome [obesity, insulin resistance type 2 (or diabetes mellitus type 2), non-alcoholic fatty liver or non-alcoholic steatohepatitis] has in recent years become a major public health problem in some resource-rich countries. A link between excess body iron and insulin resistance or the metabolic syndrome has become apparent. The metabolic syndrome may be complicated by the supervention of HCC, and recent evidence suggests that increased body iron may contribute to this complication.