HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis

J Hepatol. 2003 Mar;38(3):335-42. doi: 10.1016/s0168-8278(02)00415-4.


Background/aims: The impact of heterozygous HFE mutations on the course of chronic hepatitis C and iron indices was studied.

Methods: Ferritin, transferrin saturation (TS), serum iron, C282Y and H63D mutations were determined in 401 patients with chronic hepatitis C virus (HCV) infection and 295 healthy controls. Liver histologies were available in 217 and HCV genotypes in 339 patients.

Results: Allele frequencies of the C282Y and H63D mutation did not differ between HCV patients and healthy controls (6.95 vs. 6.2%; 14.75 vs. 16.4%; n.s.). HFE heterozygous HCV patients had higher ferritin (349+/-37 vs. 193+/-15 microg/l; P<0.0005), TS (38+/-2 vs. 32+/-1%; P<0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P<0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P<0.006) and fibrosis scores (1.9+/-0.2 vs. 1.4+/-0.1; P<0.003) compared to HFE wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P<0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P<0.05) for H63D heterozygotes compared to HFE wildtypes. Considering all HFE heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P<0.009) for cirrhosis and 3.1 (CI 1.3-7.3; P<0.009) for fibrosis were calculated.

Conclusions: C282Y or H63D heterozygosity is an independent risk factor for liver fibrosis and cirrhosis in HCV infected individuals. Screening for HFE mutations should be considered in HCV infection.

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Hemochromatosis Protein
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / pathology
  • Heterozygote*
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Iron / blood
  • Liver / pathology
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Odds Ratio


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