The H63D genetic variant of the HFE gene is independently associated with the virological response to interferon and ribavirin therapy in chronic hepatitis C.
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.
Carneiro
Marcos V
MV
Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Souza
Fernanda F
FF
Teixeira
Andreza C
AC
Figueiredo
José F C
JF
Villanova
Marcia G
MG
Secaf
Marie
M
Passos
Afonso D C
AD
Ramalho
Leandra N Z
LN
Carneiro
Fabiana P
FP
Zucoloto
Sérgio
S
Candolo Martinelli
Ana L
AL
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
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