The haemochromatosis gene: a co-factor for chronic liver diseases?

There is increasing evidence that hepatotoxins, such as alcohol and the hepatitis viruses, act as co-factors in causing hepatic fibrosis and cirrhosis. For example, alcohol aggravates the hepatic damage produced by iron in hereditary haemochromatosis. We present evidence that the reverse is also true, that is, that iron loading of mild to moderate degree due to heterozygosity or homozygosity for the haemochromatosis genetic mutations acts as a significant hepatotoxin aggravating hepatic damage from other causes of liver disease. These include non-alcoholic steatohepatitis, chronic hepatitis C, porphyria cutanea tarda and possibly primary liver cell cancer. However, any additional hepatotoxic effect is due to the hepatic iron concentration and not the mutations in the haemochromatosis genes.