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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 Sartori (sartori{at}fauser.edu)
  1. Gastroenterology Unit, Ospedale Maggiore della Caritá, Novara, Italy
    1. Silvano Andorno (andornos{at}alice.it)
    1. Gastroenterology Unit, Ospedale Maggiore della Caritá, Novara, Italy
      1. Michela Pagliarulo (pagliarulo{at}libero.it)
      1. Dept of Medical Sciences, University of East Piedmont, Novara, Italy
        1. Cristina Rigamonti (crigamo{at}libero.it)
        1. Dept of Medical Sciences, University of East Piedmont, Novara, Italy
          1. Cristina Balzola (balzocri{at}alice.it)
          1. Dept of Medical Sciences, University of East Piedmont, Novara, Italy
            1. Patrizia Pergolini (pergolini{at}maggioreosp.novara.it)
            1. Clinical Chemistry Unit, Ospedale Maggiore della Caritá, Novara, Italy
              1. Roberta Rolla (rolla{at}med.unipmn.it)
              1. Dept of Medical Sciences, University of East Piedmont, Novara, Italy
                1. Anna Suno (sunoan{at}libero.it)
                1. Clinical Chemistry Unit, Ospedale Maggiore della Caritá, Novara, Italy
                  1. Renzo Boldorini (boldorini{at}med.unipmn.it)
                  1. Dept of Medical Sciences, University of East Piedmont, Novara, Italy
                    1. Giorgio Bellomo (giorgio.bellomo{at}maggioreosp.novara.it)
                    1. Dept of Medical Sciences, University of East Piedmont, Novara, Italy
                      1. Emanuele Albano (albano{at}med.unipmn.it)
                      1. Dept of Medical Sciences, University of East Piedmont, Novara, Italy

                        Abstract

                        Background: Iron accumulation is a well known risk factor for the progression of chronic hepatitis C (CHC) to fibrosis. However, the pro-fibrogenic role of the genes controlling iron homeostasis is still controversial. In this work we have evaluated the relative role of HFE, ferroportin, and β-globin genes 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-Ab, HBsAg 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 7bp 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, while 58 had the wild-type alleles of both the genes. Hepatic iron concentration and hepatic stainable iron were significantly higher (p<0.05) in CHC patients 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 hepatic iron concentration (p=0.008) and hepatic stainable iron (OR 6.11; 95%CI 1.56-23.92; p=0.009). Moderate/severe fibrosis or cirrhosis (Ishak's score>2) was observed in 48/100 patients. Logistic regression demonstrated that age (OR 1.05; 95%CI 1.02-1.09; p<0.005) and β-globin mutations (OR 4.99; 95%CI. 1.22-20.3; 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 CHC patients.

                        • HCV infection
                        • iron overload
                        • liver cirrhosis
                        • oxidative stress
                        • thalassemic trait

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