title: Metal contents in the liver of patients with chronic liver disease caused by hepatitis C virus. Reference to hepatocellular carcinoma.
abstract: OBJECTIVE
  The aim of this study was to investigate the relationship between trace metals and the prevalence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis or hepatic cirrhosis caused by hepatitis C virus (HCV).
  
  
  METHODS
  We measured the contents of copper, iron, and zinc in HCC tissue (n = 112), dysplastic nodules (n = 7), and liver parenchyma in patients with (n = 112) and without (n = 12; 7 with grade F3 fibrosis, 5 with grade F4 fibrosis) HCC. Metals were quantified in thin-needle biopsy specimens using the particle-induced X-ray emission method (PIXE).
  
  
  RESULTS
  Copper level in liver parenchyma was higher in patients with HCC than in those without HCC (p < 0.01), while there was no such difference in hepatic iron. In patients with grade F4 fibrosis, copper content in the liver parenchyma was higher in the presence of HCC than in its absence (p < 0.05). Multiple regression analysis showed that the only factor significantly associated with the coexistence of HCC in HCV-positive patients with chronic liver disease was the copper level in the liver parenchyma.
  
  
  CONCLUSIONS
  Hepatic copper overload may contribute to the development of HCC in HCV-positive patients with chronic hepatitis or cirrhosis.
authors.affiliation: Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan. ebara@med.m.chiba-u.ac.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ebara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukuda
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hatano
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sugiura
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Saisho
authors.forename: Fukuo
authors.initials: F
authors.lastname: Kondo
authors.forename: Masae
authors.initials: M
authors.lastname: Yukawa
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000209:etiology* / Q000473:pathology / Q000821:virology; D003300:Copper / Q000032:analysis*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D058085:Iron Compounds / Q000032:analysis; D008099:Liver / Q000737:chemistry*; D008113:Liver Neoplasms / Q000737:chemistry* / Q000209:etiology* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D017967:Zinc Compounds / Q000032:analysis
chemical_list: D058085:Iron Compounds; D017967:Zinc Compounds; D003300:Copper