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

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 μg/l; P<0.0005), TS (38±2 vs. 32±1%; P<0.0005), serum iron (144±6 vs. 121±3 μg/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.