EASL Clinical Practice Guidelines

Recommendations for the diagnosis of HFE-HC:

  • Patients with suspected iron overload should first receive measurement of fasting transferrin saturation and serum ferritin (1B), and HFE testing should be performed only in those with increased transferrin saturation (1A).
  • Patients from liver clinics should be screened for fasting transferrin saturation and serum ferritin (1C) and offered genetic HFE testing if transferrin saturation is increased (1B).
  • HFE testing for the C282Y and H63D polymorphism should be carried out in all patients with otherwise unexplained increased serum ferritin and increased transferrin saturation (1B).
  • Diagnosis of HFE hemochromatosis should not be based on C282Y homozygosity alone, but requires evidence of increased iron stores (1B).
  • C282Y/H63D compound heterozygotes and H63D homozygotes presenting with increased serum ferritin (>200 μg/L in females, >300 μg/L in males), increased transferrin saturation (>45% in females, >50% in males) or increased liver iron should first be investigated for other causes of hyperferritinemia (1C).
  • In C282Y homozygote patients with increased iron stores, liver biopsy is no longer necessary to diagnose hemochromatosis. Liver biopsy could be offered to C282Y homozygous patients with serum ferritin above 1000 μg/L, elevated AST, hepatomegaly, or age over 40 years (1C).
  • Genetic testing of 'other hemochromatosis genes' (TFR2, SLC40A1, HAMP, HJV) could be considered in patients with increased iron stores after exclusion of C282Y homozygosity if (i) iron excess has been proven by direct assessment, i.e. by MRI or liver biopsy, and (ii) other hepatic and haematological disorders have been ruled out (2C).
  • According to the autosomal recessive transmission of HFE-HC, genetic testing of siblings of individuals with HFE-HC should be carried out. Genetic testing of other 1st degree relatives should be considered (1B). (Practical and cost effective strategies for family screening have been published [206].)