title: Hemochromatosis gene mutations: prevalence and effects on pegylated-interferon and ribavirin therapy response in chronic hepatitis C in sardinia.
abstract: OBJECTIVE
  Considerable evidence suggests that iron could be a comorbid factor for liver injury in chronic hepatitis C (CHC). Elevated iron indices are frequently described in CHC and may impact negatively on the course of liver disease and on the response to interferon alfa therapy. The aim of this study was to evaluate the frequency of hemochromatosis gene mutations in Sardinian CHC patients, the association with iron overload and the impact on response to therapy.
  
  
  METHODS
  Sixty-nine CHC patients were enrolled. Iron indices, hepatic and viral parameters were detected. C282Y, H63D and S65C mutations were identified through a PCR. Liver biopsy was performed for hepatic fibrosis evaluation. All patients were treated for 6 months (viral genotype 2/3) or 12 months (viral genotype 1/4) with pegylated-interferon 180 mcg once weekly and ribavirin 1000-1200 mg/daily. Sustained virological response (SVR) was defined as undetectable HCV RNA 24 weeks after the end of treatment.
  
  
  RESULTS
  HFE gene mutation was detected in 29 patients (42%). The presence of HFE mutations was significantly associated with elevated transferrin saturation (P < 0.01). Hepatic fibrosis was more advanced in HFE mutation carriers (χ (2), P = 0.04). Among mutation carriers 27.5% achieved responses at the end of treatment compared with 60% of non-carriers (P = 0.005). Patients with HFE wildtype produced significant SVR compared with patients with HFE mutations (P = 0.03).
  
  
  CONCLUSIONS
  The literature shows discordant results about the prevalence, hepatic distribution and possible therapeutic implications of iron overload in chronic hepatitis C. Our findings shows that HFE gene mutations could favor, synergically with CHC and other genetic or acquired factors, the development of liver damage and could influence the outcome of interferon treatment with higher rate of non-response.
authors.affiliation: Department of Gastroenterology, Azienda Ospedaliero-Universitaria di Cagliari, SS 554 bivio per Sestu, 09130 Cagliari, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Sini
authors.affiliation: Department of Gastroenterology, Azienda Ospedaliero-Universitaria di Cagliari, SS 554 bivio per Sestu, 09130 Cagliari, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Sorbello
authors.affiliation: Department of Gastroenterology, Azienda Ospedaliero-Universitaria di Cagliari, SS 554 bivio per Sestu, 09130 Cagliari, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Civolani
authors.affiliation: Department of Gastroenterology, Azienda Ospedaliero-Universitaria di Cagliari, SS 554 bivio per Sestu, 09130 Cagliari, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Demelia
keywords: ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate aminotransferase; CHC, Chronic hepatitis C; ETR, End of treatment response; GGT, g-glutamyl transpeptidase; HCV, Hepatitis virus C infection determination; HFE gene; HFE, Human hemochromatosis protein; HH, Hereditary Hemochromatosis; SVR, Sustained virologic response; TSI, Transferin saturation index; ULN, Upper normal limit; WT, wildtype; iron overload; viral hepatitis