Influence of HFE gene polymorphism on the progression and treatment of chronic hepatitis C.
We analysed liver histology findings in a large cohort of patients with chronic hepatitis C and in roughly half of them their response to interferon-alpha-based on iron parameters and HFE status. Histological activity and virological response to antiviral therapy (n = 146) were analysed in 273 immunocompetent and nonalcoholic patients with chronic hepatitis C, in terms of serum iron load, intrahepatic iron load (n = 110) and HFE mutations. Patients who were heterozygous for the C282Y and H63D mutations exhibited higher iron serum parameters than subjects without these mutations. The intrahepatic iron load was higher in H63D patients only. No association was observed between HFE mutations and histological activity. Increased iron parameters were associated with liver disease severity by univariate analysis only. Genotype 1 and ferritinaemia were associated with a poor response to antiviral therapy, whereas the H63D mutation emerged as a positive predictive factor for end of treatment and sustained antiviral response. Therefore, in chronic hepatitis C patients serum and intrahepatic iron levels were weakly correlated with histological activity, while HFE mutations were not. As for the response to interferon-alpha, elevated ferritinaemia constituted a negative predictive factor whereas the H63D mutation was a positive one. The H63D mutation might form part of an immunogenetic profile influencing the response to interferon therapy.
Unité d'Hépatologie, CHU Necker, Paris, France.
P
P
Lebray
H
H
Zylberberg
S
S
Hue
B
B
Poulet
F
F
Carnot
S
S
Martin
Y
Y
Chretien
S
S
Pol
S
S
Caillat-Zuckman
C
C
Bréchot
B
B
Nalpas
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D000071020:Hemochromatosis Protein; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007501:Iron / Q000032:analysis / Q000097:blood; D019190:Iron Overload; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome
D000998:Antiviral Agents; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D008565:Membrane Proteins; D012367:RNA, Viral; D005293:Ferritins; D007501:Iron