HFE C282Y gene variant is a risk factor for the progression to decompensated liver disease in chronic viral hepatitis C subjects in the Czech population

Abstract

Aim: To determine the prevalence of selected HFE polymorphisms (C282Y, H63D and S65C) among patients with chronic viral hepatitis B and C and to investigate their role in the progression of liver disease. Methods: A total of 207 subjects with chronic B or C viral hepatitis and 243 healthy controls were enrolled in the case-control study. Cases were further classified into three groups according to the clinical stage of liver disease: (A) virus carriers; (B) compensated liver disease; and (C) decompensated liver disease. HFE polymorphisms were detected by polymerase chain reaction-based methodology. Fisher's exact test, χ2 and Kruskal-Wallis tests were used to test for differences in variables studied between groups. Haplotypes were inferred in silico and their distribution compared by permutation test. Modified survival (time-to-event) analysis was used to test for the differences in the progression to the decompensated liver disease in carriers of C282Y wild-type versus mutated genotypes. Results: The frequency of HFE genotypes, alleles and haplotypes differed neither between HBV nor HCV patients versus controls. In HCV subjects: (i) the frequency of the 282Y allele was significantly higher in the (C) group compared to (B) group (12.5 vs 2.2%, respectively, P = 0.002, Fisher's exact test); and (ii) carriers of the 282Y mutation exhibited significantly faster progression to decompensated liver disease than wild-type carriers (P = 0.044, log-rank test). Conclusion: Carriage of the minor HFE C282Y polymorphism is associated with decompensated liver disease and its earlier onset in the subjects with chronic viral hepatitis C in the Czech population. © 2007 The Japan Society of Hepatology.