title: Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin.
abstract: BACKGROUND
  Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy.
  
  
  OBJECTIVE
  To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin.
  
  
  METHODS
  A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks.
  
  
  RESULTS
  Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test).
  
  
  CONCLUSIONS
  Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.
authors.affiliation: Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Silvia
authors.initials: S
authors.lastname: Coelho-Borges
authors.forename: Hugo
authors.initials: H
authors.lastname: Cheinquer
authors.forename: Fernando Herz
authors.initials: FH
authors.lastname: Wolff
authors.forename: Nelson
authors.initials: N
authors.lastname: Cheinquer
authors.forename: Luciano
authors.initials: L
authors.lastname: Krug
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D005293:Ferritins / Q000097:blood*; D005838:Genotype; D000071020:Hemochromatosis Protein; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012367:RNA, Viral; D012254:Ribavirin; D005293:Ferritins; D007372:Interferons