title: Threshold effect of liver iron content on hepatic inflammation and fibrosis in hepatitis B and C.
abstract: OBJECTIVE
  In hepatitis C, iron depletion may improve serum aminotransferases and the response to interferon, but it is not known whether inflammation and fibrosis correlate with hepatic iron content. Our aim was to establish whether hepatic iron content correlates with histological and serum indices of hepatic inflammation and fibrosis in hepatitis B and C.
  
  
  METHODS
  Total hepatic iron was measured using computerized histomorphometry, and hepatic inflammation and fibrosis using a modified Knodell score, on histological slides from 31 patients with chronic hepatitis B and 38 with hepatitis C.
  
  
  RESULTS
  Total hepatic iron was similar in the hepatitis B and C groups (0.82 +/- 1.72% and 0.56 +/- 1.12%; mean +/- SD). No iron was detectable in 11 patients with hepatitis B and 13 with hepatitis C. Alanine aminotransferase (85.96 +/- 67.1 vs 44.2 +/- 39.7 p < 0.05), aspartate aminotransferase (93.8 +/- 75.6 vs 47 +/- 33.5 IU/ml p < 0.05) and histological inflammatory score (9.33 +/- 3.51 vs 7.79 +/- 3.3 p = 0.07) were increased in those with stainable hepatic iron compared to those without. However, where iron was present, no association was found between the amount of hepatic iron and inflammatory or fibrosis scores. In hepatitis C, fibrosis was minimal in 77% of patients if iron was absent vs 24% with iron present, while marked fibrosis was present in 56% with iron vs 15% without iron (p < 0.01, Fisher's exact test).
  
  
  CONCLUSIONS
  Hepatic iron is associated with increased hepatic inflammation in chronic hepatitis B and hepatitis C and with high fibrosis scores in hepatitis C. There is a threshold effect, and once present, increasing iron does not correlate with increasing inflammation or fibrosis.
authors.affiliation: MRC/UCT Liver Research Centre, Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: N K
authors.initials: NK
authors.lastname: Beinker
authors.forename: M D
authors.initials: MD
authors.lastname: Voigt
authors.forename: M
authors.initials: M
authors.lastname: Arendse
authors.forename: J
authors.initials: J
authors.lastname: Smit
authors.forename: I A
authors.initials: IA
authors.lastname: Stander
authors.forename: R E
authors.initials: RE
authors.lastname: Kirsch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D005260:Female; D006509:Hepatitis B / Q000097:blood / Q000378:metabolism*; D006526:Hepatitis C / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D012044:Regression Analysis
chemical_list: D007501:Iron