title: The H63D genetic variant of the HFE gene is independently associated with the virological response to interferon and ribavirin therapy in chronic hepatitis C.
abstract: BACKGROUND
  Conflicting results have been reported in studies evaluating the relationship between serum markers of iron overload, liver iron deposits, and HFE mutations (C282Y and H63D) in chronic hepatitis C patients, and also their impact on the response to therapy in these patients.
  
  
  OBJECTIVE
  To evaluate the role of HFE mutations in the severity of liver disease and in the response to therapy in chronic hepatitis C.
  
  
  METHODS
  Two hundred and sixty-four hepatitis C patients treated with standard interferon and ribavirin were divided into two groups according to type of antiviral response: sustained virological response (SVR) and nonresponse or relapse. We evaluated the relationship between HFE mutation and the type of antiviral response, clinical data, biochemical tests, liver histopathology, virological data, and HFE mutations.
  
  
  RESULTS
  Of the 264 patients, 88 (32.1%) had SVR whereas 67.9% had nonresponse or relapse. Liver iron deposits were observed in 49.2% of the patients. The factors associated with SVR were hepatitis C virus genotype 2 or 3, transferrin saturation value of 45% or less, and detection of the H63D mutation. HFE mutation was more frequent in patients with iron deposits, but without association with serum iron biochemistry or severity of liver disease. Steatosis was more frequent in patients with liver iron deposits. CONCLUSION THE: H63D mutation was an independent factor associated with SVR in chronic hepatitis C patients, as also were hepatitis C virus genotype 2 or 3 and transferrin saturation value of 45% or less. Moreover, the H63D mutation was associated with liver iron deposits.
authors.affiliation: Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marcos V
authors.initials: MV
authors.lastname: Carneiro
authors.forename: Fernanda F
authors.initials: FF
authors.lastname: Souza
authors.forename: Andreza C
authors.initials: AC
authors.lastname: Teixeira
authors.forename: José F C
authors.initials: JF
authors.lastname: Figueiredo
authors.forename: Marcia G
authors.initials: MG
authors.lastname: Villanova
authors.forename: Marie
authors.initials: M
authors.lastname: Secaf
authors.forename: Afonso D C
authors.initials: AD
authors.lastname: Passos
authors.forename: Leandra N Z
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Fabiana P
authors.initials: FP
authors.lastname: Carneiro
authors.forename: Sérgio
authors.initials: S
authors.lastname: Zucoloto
authors.forename: Ana L
authors.initials: AL
authors.lastname: Candolo Martinelli
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D000071020:Hemochromatosis Protein; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D015995:Prevalence; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D000998:Antiviral Agents; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008565:Membrane Proteins; D011994:Recombinant Proteins; D012254:Ribavirin; D007501:Iron