Introduction

The amount of body iron stores is a major determinant of clinical outcome in patient with hemochromatosis. Patients with greater iron overload, as assessed by hepatic iron concentration (HIC) and/or the amount of total iron removed by phlebotomy (IR), have an increased prevalence of diabetes, cardiomyopathy and hypogonadism and an increased risk of mortality. HIC greater than 400–500 mmol/g is an important risk factor for hepatic fibrosis and cirrhosis. In contrast, arthropathy is unrelated to iron stores and, unlike other clinical manifestations, is not significantly improved by phlebotomy therapy. It is generally accepted that the liver is the first site of iron deposition in persons with hemochromatosis, and that other organs are involved later. Previous studies have suggested that there may be a threshold in the liver for iron accumulation. Mandelli et al. showed that the increases of HIC became progressively smaller until HIC plateaus at a value of ∼350 mmol, after which iron accumulation progresses in extrahepatic sites as shown by the increase of both serum ferritin concentration and IR, and by the higher frequency of clinical extrahepatic manifestations excluding arthropathy.

Factors affecting the expression of iron overload

The degree of iron overload and the related clinical complications vary widely in hemochromatosis and both acquired and genetic factors influence phenotypic expression of the disease.