Hemochromatosis and transferrin receptor gene polymorphisms in chronic hepatitis C: impact on iron status, liver injury and HCV genotype

J Mol Med (Berl). 2003 Dec;81(12):780-7. doi: 10.1007/s00109-003-0493-0. Epub 2003 Oct 14.


Mild iron overload in chronic hepatitis C is associated with liver fibrosis, hepatitis C virus (HCV) genotype 1b infection, and an impaired response to interferon therapy. In this study we evaluated whether polymorphisms in the hemochromatosis gene HFE and the transferrin receptor gene TFR1 are associated with these typical findings. The study considered 246 HCV-infected patients and 200 blood donors as controls, in which C282Y, H63D, and S65C mutations ( HFE) and the S142G polymorphism ( TFR1) were detected. HCV genotype, serum ferritin levels, stainable intrahepatic iron, and grade of fibrosis according to the METAVIR score (F0-F4) were determined. In HCV-infected patients, heterozygosity for the C282Y mutation in HFE was significantly associated with elevated serum ferritin levels, stainable liver iron, and advanced fibrosis or cirrhosis (F2-F4). By multivariate logistic regression analysis the odds ratio for the development of advanced fibrosis or cirrhosis (F2-F4) was 2.5 for HCV-infected patients carrying a heterozygous C282Y mutation and 4.8 for HCV-infected patients with C282Y/H63D and C282Y/S65C compound heterozygosity. Heterozygosity for the C282Y mutation in HFE contributes to iron accumulation and fibrosis progression in chronic hepatitis C.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD
  • Female
  • Genotype
  • Hemochromatosis / genetics
  • Hemochromatosis Protein
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Iron Overload / genetics*
  • Iron Overload / virology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / virology
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Polymorphism, Genetic
  • Prognosis
  • Receptors, Transferrin / genetics*


  • Antigens, CD
  • CD71 antigen
  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Receptors, Transferrin