title: Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C.
abstract: OBJECTIVE
  HFE mutations, a common cause of hereditary hemochromatosis (HH), are reportedly associated with hepatic iron overload, severe liver fibrosis, and good response to interferon treatment in European patients with chronic hepatitis C (CHC). HH shows ethnicity-based differences and little is known about the effects of HH mutations on CHC in the Japanese. Thus, the aim of this study was to clarify the clinical influence of HFE mutations in Japanese CHC patients.
  
  
  METHODS
  In a total of 251 patients with CHC, we analyzed the frequencies of H63D and S65C mutations in the HFE gene, and the influence of these mutations on clinical parameters and response to pegylated-interferon-alpha 2b (PEG-IFN) plus ribavirin therapy.
  
  
  RESULTS
  Fourteen patients (5.6%) carried the H63D mutation; all were heterozygotes. No S65C mutations were found. Only hemoglobin levels in the H63D heterozygotes were higher than in wild-type patients. Eleven of 14 H63D heterozygotes achieved sustained virological response (SVR). On univariate analysis, factors associated with SVR were interleukin 28B (IL28B) polymorphism, age, hepatitis C virus (HCV) genotype, HCV viral load, white blood cell count, stage of fibrosis and H63D mutation. All patients with both TT genotype in IL28B (rs8099917) and H63D mutation in HFE (n = 10) achieved SVR.
  
  
  CONCLUSIONS
  The H63D mutation has little impact on the clinical characteristics of CHC, but is related to favorable response to PEG-IFN plus ribavirin therapy, particularly in patients with the TT allele in IL28B.
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ishizu
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Katano
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishigami
authors.forename: Akihiro
authors.initials: A
authors.lastname: Itoh
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Isao
authors.initials: I
authors.lastname: Nakano
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D000071020:Hemochromatosis Protein; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D019190:Iron Overload / Q000235:genetics / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
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; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b