1. HFE mutations and chronic hepatitis C: H63D and C282Y heterozygosity are independent risk factors for liver fibrosis and cirrhosis
- Author
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Claus Niederau, Claudia Mellenthin, Andreas Donner, Andreas Erhardt, Reinhard Willers, Günther Kappert, Dieter Häussinger, Andrea Maschner-Olberg, and Ortwin Adams
- Subjects
Adult ,Liver Cirrhosis ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Heterozygote ,Cirrhosis ,Hepatitis C virus ,Iron ,medicine.disease_cause ,Loss of heterozygosity ,Gene Frequency ,Odds Ratio ,Medicine ,Humans ,Genetic Predisposition to Disease ,Hemochromatosis Protein ,Allele frequency ,Hemochromatosis ,Alleles ,Hepatology ,biology ,medicine.diagnostic_test ,business.industry ,Transferrin saturation ,Histocompatibility Antigens Class I ,nutritional and metabolic diseases ,Membrane Proteins ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Ferritin ,Liver ,Case-Control Studies ,Immunology ,Mutation ,biology.protein ,Serum iron ,Female ,business - Abstract
The impact of heterozygous HFE mutations on the course of chronic hepatitis C and iron indices was studied.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.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; P0.0005), TS (38+/-2 vs. 32+/-1%; P0.0005), serum iron (144+/-6 vs. 121+/-3 microg/dl; P0.0005), semiquantitative liver iron staining (0.26+/-0.07 vs. 0.09+/-0.03; P0.006) and fibrosis scores (1.9+/-0.2 vs. 1.4+/-0.1; P0.003) compared to HFE wildtypes. By multivariate regression analysis odds ratios for liver cirrhosis were 5.9 (confidence interval (CI) 1.6-22.6; P0.009) for C282Y heterozygotes and 2.9 (CI 1.0-8.4; P0.05) for H63D heterozygotes compared to HFE wildtypes. Considering all HFE heterozygous HCV patients, odds ratios of 3.6 (CI 1.4-9.3; P0.009) for cirrhosis and 3.1 (CI 1.3-7.3; P0.009) for fibrosis were calculated.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.
- Published
- 2003