title: Liver iron accumulation in chronic hepatitis C patients without HFE mutations: relationships with histological damage, viral load and genotype and alpha-glutathione S-transferase levels.
abstract: BACKGROUND
  Host and viral factors have been suggested as possible causative factors for the presence of liver iron accumulation in chronic hepatitis C. However, there is no agreement regarding the influence of liver iron accumulation on the biochemical and histological severity of chronic hepatitis C. Moreover, data concerning the relationships between both viral load and genotype and liver iron accumulation are scanty.
  
  
  OBJECTIVE
  To evaluate the biochemical, histological and virological assessment of a group of chronic hepatitis C patients without risk factors for iron overload, on the basis of the presence, degree and distribution of liver iron accumulation.
  
  
  METHODS
  Fifty-three chronic hepatitis C patients (34 men, 19 women; age 44 +/- 11 years) with no risk factors for liver iron accumulation and showing no HFE mutations were chosen from a broader cohort of chronic hepatitis C patients. The presence, degree and distribution of liver iron accumulation were assessed using Deugnier's score. Relationships between the presence of liver iron accumulation and grading and staging were carried out separately. Hepatitis C virus RNA serum levels and viral genotype were compared in patients with or without liver iron accumulation. Alpha glutathione S-transferase serum levels were assessed in all patients.
  
  
  RESULTS
  Overall, liver iron accumulation was mild and was present in 19 patients (36%). It was associated with male gender (P = 0.0358), and was reflected by high serum iron levels (P = 0.001) and high ferritin levels (P < 0.0001). Hepatitis C virus RNA levels and genotype were not associated with the presence of liver iron accumulation. In multivariate analysis, ferritin was the only variable significantly associated with liver iron accumulation (P < 0.0001). Grading was higher in patients with liver iron accumulation regardless of the site of iron deposition. Fibrosis was present in all patients with iron overload; these patients were more frequently cirrhotic. Moreover, patients with mesenchymal or mixed deposition had higher staging than patients with hepatocytic or no iron deposition. This feature was reflected by higher alpha-glutathione S-transferase levels.
  
  
  CONCLUSIONS
  Liver iron accumulation is mild in chronic hepatitis C patients without HFE mutations and is mainly reflected by serum ferritin levels. Viral characteristics do not seem to play a role in iron deposition. Liver iron accumulation is associated with higher grading, advanced fibrosis and cirrhosis. Moreover, higher staging is associated with mesenchymal or mixed iron deposition. In these patients, higher alpha-glutathione S-transferase levels seem to reflect more complex damage.
authors.affiliation: Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Giannini
authors.forename: L
authors.initials: L
authors.lastname: Mastracci
authors.forename: F
authors.initials: F
authors.lastname: Botta
authors.forename: P
authors.initials: P
authors.lastname: Romagnoli
authors.forename: A
authors.initials: A
authors.lastname: Fasoli
authors.forename: D
authors.initials: D
authors.lastname: Risso
authors.forename: F
authors.initials: F
authors.lastname: Faravelli
authors.forename: P
authors.initials: P
authors.lastname: Ceppa
authors.forename: P B
authors.initials: PB
authors.lastname: Lantieri
authors.forename: G C
authors.initials: GC
authors.lastname: Icardi
authors.forename: R
authors.initials: R
authors.lastname: Testa
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D007501:Iron; D005982:Glutathione Transferase