Clinical impact of HFE Mutations in portuguese patients with Chronic Hepatitis C

INTRODUCTION: Chronic hepatitis C (CHC) is often associated with alterations in iron and lipid metabolisms, which may affect the long-term prognosis and the response to antiviral treatment. Some studies suggested that the occurrence of HFE mutations may contribute to modulate these metabolisms in CHC. Here, the prevalence of two HFE mutations (C282Y and H63D) was determined in a group of Portuguese CHC patients and the findings were correlated with clinical, histological and virulogical features. MATERIALS AND METHODS: 183 CHC patients (118 males and 65 females), mean age 45.84±11.46 years and IMC 25.45±3.96 Kg/m2. Eighty two (44.8%) were treated with standard antiviral therapy and divided into 3 groups: non response (NR)-25.6%, relapse (RR)-9.8% and sustained response (SR)-64.6%. HCV-RNA and genotype were determined by PCR. Liver steatosis, fibrosis stage and degree of necroinflammation (grading) were assessed by liver biopsy (Peter Scheuer score) and clinical parameters were measured by standard techniques: AST, ALT, GGT, lipid profile (LDL, HDL, total cholesterol and triglycerides), iron metabolism (iron, ferritin, transferrin and transferrin saturation), haptoglobin, ceruloplasmin, insulin, glucose, peptide-C and HOMA. Antioxidant potential (tGSH/GSSG ratio) was evaluated by spectrofluorimetry. HFE_H63D and C282Y polymorphisms were analyzed by PCR-RFLP and statistical analysis was performed with SPSS 16.0 (level of significance of p<0.05). Patients’ exclusion criteria: other chronic liver diseases, alcohol ingestion >40g/day, HIV infection, metabolic and autoimmune diseases. RESULTS: Sixty two patients (33.9%) carried one or two mutant H63D allele (HD+DD), being 4.4% homozygous (DD). C282Y polymorphism was present in 5.5% of the patients; all were heterozygous. No difference was found comparing HFE_H63D and _C282Y polymorphisms with the type of antiviral response. Regarding H63D, we observe a decrease in the degree of necroinflammation (grading) and in tGSH/GSSG ratio and an increase in total cholesterol for carriers of the mutant allele (HD+DD) comparing to HH individuals (p=0.004; p=0.006; p=0.042, respectively). For C282Y, our study revealed that heterozygous CY had higher serum iron and transferrin saturation levels (p=0.038; p=0.006, respectively) and lower total cholesterol (p