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26 February 2010

The role of iron overload and HFE gene mutations in the era of pegylated interferon and ribavirin treatment of chronic hepatitis C

Katarzyna SikorskaABCDEFG, Piotr StalkeBCE, Ewa Izycka-SwieszewskaBD, Tomasz RomanowskiBDEG, Krzysztof Piotr BielawskiEG

Med Sci Monit 2010; 16(3): CR137-143 :: ID: 878463

Abstract

Background
Iron overload observed in chronic hepatitis C (CHC) has been suggested to be one of the negative prognostic factors influencing liver disease progression and failure of treatment with recombinant interferon in monotherapy or in combination with ribavirin. The aim of this study was to assess occurrence of iron overload in relation to polymorphism of the HFE and the influence of both these factors on efficacy of antiviral treatment with pegylated interferon and ribavirin in patients with CHC.
Material and Method
Liver function tests, serum indices of iron metabolism, and HFE mutations were assayed in 152 patients with CHC from Poland. Histopathological examination of the liver biopsy specimen was performed in 138 patients. Sixty-one patients were treated with pegylated interferon alfa-2 and ribavirin. The comparative analysis was performed in 2 groups of patients: those with and those without elevated serum indices of iron metabolism.
Results
Increased biochemical iron metabolism parameters correlated with older age, higher ALT activity, more advanced liver fibrosis and treatment failure. Iron deposits in liver specimens were not accompanied by exacerbation of necro-inflammatory activity and advanced fibrosis. Elevated biochemical values of iron metabolism parameters and presence of hepatic iron deposits correlated positively with C282Y mutations. The lack of sustained viral response after treatment with pegylated interferon and ribavirin was observed more frequently in carriers of HFE mutations.
Conclusions
Iron overload was frequently detected in patients with CHC, and was associated only with C282Y alleles. Biochemical markers of iron overload and HFE gene mutations were negative prognostic factors of antiviral treatment.

Keywords: Polymorphism, Single Nucleotide - genetics, Polyethylene Glycols - therapeutic use, Poland, Mutation - genetics, Membrane Proteins - genetics, Liver Cirrhosis - genetics, Iron Overload - complications, Iron - metabolism, Interferon-alpha - therapeutic use, Histocompatibility Antigens Class I - genetics, Hepatitis C, Chronic - pathology, Demography, Case-Control Studies, Antiviral Agents - therapeutic use, Adolescent, Recombinant Proteins, Ribavirin - therapeutic use, young adult

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Medical Science Monitor eISSN: 1643-3750