Correlates of hepcidin and NTBI according to HFE status in patients referred to a liver centre

Acta Haematol. 2015;133(2):155-61. doi: 10.1159/000363490. Epub 2014 Sep 26.


Background/aims: Innately low hepcidin levels lead to iron overload in HFE-associated hereditary haemochromatosis.

Methods: This study compared hepcidin and non-transferrin bound iron (NTBI) levels in untreated iron-loaded and non-iron-loaded C282Y homozygotes to levels in C282Y/H63D compound heterozygotes and individuals with other HFE genotypes associated with less risk of iron overload.

Results: As the genotypic risk for iron overload increased, transferrin saturation and serum NTBI levels increased while serum hepcidin levels decreased. Overweight and obese male C282Y homozygotes had significantly higher hepcidin levels than male C282Y homozygotes with a normal BMI. Pearson product-moment analysis showed that serum hepcidin levels significantly correlated with HFE status, serum ferritin, age, NTBI, transferrin saturation, gender and BMI. Subsequent multiple regression analysis showed that HFE status and serum ferritin were significant independent correlates of serum hepcidin levels.

Conclusions: In summary, this study has shown that while serum ferritin and HFE status are the most important determinants of hepcidin levels, factors such age, gender, BMI, transferrin saturation and NTBI all interact closely in the matrix of homeostatic iron balance.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Amino Acid Substitution
  • Female
  • Ferritins / blood*
  • Hemochromatosis / blood*
  • Hemochromatosis / genetics
  • Hemochromatosis Protein
  • Hepcidins / blood*
  • Hepcidins / genetics
  • Histocompatibility Antigens Class I / blood
  • Histocompatibility Antigens Class I / genetics*
  • Homozygote*
  • Humans
  • Iron / blood*
  • Iron Overload / blood
  • Iron Overload / etiology
  • Iron Overload / genetics
  • Male
  • Membrane Proteins / blood
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation, Missense*
  • Obesity / blood
  • Obesity / genetics
  • Risk Factors
  • Sex Factors


  • HFE protein, human
  • Hemochromatosis Protein
  • Hepcidins
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Ferritins
  • Iron