Iron Overload and HFE Mutations: Are They Relevant in Cryptogenic Cirrhosis?

Hereditary hemochromatosis (hh) is the most frequent genetic disease in populations of european origin. the hh gene was cloned by feder et al. in 1996, and 2 major mutations were discovered: c282y and h63d. geographical differences with mutation frequencies have been published (1, 2) with a decreasing gradient of occurrence in europe from north to south. hh leads to liver iron overload and raised liver iron concentration (lic) is associated with liver fibrosis. when the lic reaches 60μmol/g, or approximately twice the upper limit of the normal range (36μmol/g), activation of stellate cells appears. these cells are principally responsible for the beginning of liver fibrosis and fibrosis (3).