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Heterozygous β-globin gene mutations as a risk factor for iron accumulation and liver fibrosis in chronic hepatitis C
  1. Massimo Sartori1,
  2. Silvano Andorno1,
  3. Michela Pagliarulo1,
  4. Cristina Rigamonti2,
  5. Cristina Bozzola2,
  6. Patrizia Pergolini3,
  7. Roberta Rolla2,
  8. Anna Suno3,
  9. Renzo Boldorini2,
  10. Giorgio Bellomo2,
  11. Emanuele Albano2
  1. 1Gastroenterology Units, Ospedale Maggiore della Carità, Novara, Italy
  2. 2Department of Medical Sciences, University “Amedeo Avogadro” of East Piedmont, Novara, Italy
  3. 3Clinical Chemistry Units, Ospedale Maggiore della Carità, Novara, Italy
  1. Correspondence to:
    Professor E Albano
    Department of Medical Sciences, University “Amedeo Avogadro” of East Piedmont, Via Solaroli 17, 28100 Novara, Italy; albano{at}


Background: Iron accumulation is a well-known risk factor for the progression of chronic hepatitis C (CHC) to fibrosis. However, the profibrogenic role of the genes controlling iron homeostasis is still controversial.

Aim: To evaluate the relative role of haemachromatosis (HFE), ferroportin and β-globin gene mutations in promoting iron accumulation and fibrosis in patients with CHC.

Methods: Genetic analysis was performed together with the assessment of hepatic iron content and histology in 100 consecutive HIV-antibody and hepatitis B surface antigen-negative patients with biopsy-proven CHC.

Results: Among the patients investigated, 12 were heterozygous for various β-globin gene mutations (39[C→T], IVS1.1[G→A], 22 7 bp deletion and IVS1.6[T→C]) and 29 carried HFE (C282Y, H63D and S65C) gene mutations. One further patient was heterozygous for both HFE (H63D) and β-globin (39[C→T]) variants, whereas 58 had the wild-type alleles of both the genes. Hepatic iron concentration (HIC) and hepatic stainable iron were significantly higher (p<0.05) in patients with CHC carrying β-globin mutations than in those with HFE mutations or the wild-type alleles. Multivariate analysis confirmed that the presence of β-globin mutations was independently associated with both HIC (p = 0.008) and hepatic-stainable iron (odds ratio (OR) 6.11; 95% CI 1.56 to 23.92; p = 0.009). Moderate/severe fibrosis or cirrhosis (Ishak’s score >2) was observed in 48 of 100 patients. Logistic regression demonstrated that age (OR 1.05; 95% CI 1.02 to 1.09; p<0.005) and β-globin mutations (OR 4.99; 95% CI 1.22 to 20.3; p = 0.025) were independent predictors of the severity of fibrosis.

Conclusions: Heterozygosis for β-globin mutations is a novel risk factor for both hepatic iron accumulation and the progression to fibrosis in patients with CHC.

  • CHC, chronic hepatitis C
  • FPN1, ferroportin 1
  • HCV, hepatitis C virus
  • HFE, haemachromatosis
  • HIC, hepatic iron concentration
  • TFR2, transferrin receptor 2

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  • Published Online First 27 November 2006

  • Competing interests: None.

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