title: Iron levels in hepatocytes and portal tract cells predict progression and outcomes of patients with advanced chronic hepatitis C.
abstract: OBJECTIVE
  Iron may influence severity and progression of non-hemochromatotic liver diseases. Our aim was to assess the relationship of iron and HFE genetic variations to progression and outcomes in the HALT-C Trial and whether PegIFN therapy influenced iron variables.
  
  
  METHODS
  Participants were randomized to receive long-term PegIFN [n = 400] or no therapy [n = 413] for 3.5 y, with follow-up for up to 8.7 y [median 6.0 y]. Associations of patient characteristics with iron variables at baseline and over time were carried out using Kaplan-Meier analyses, Cox regression models, and repeated measures analysis of covariance.
  
  
  RESULTS
  Participants who developed clinical outcomes [CTP > 7, ascites, encephalopathy, variceal bleeding, SBP, HCC, death] had significantly higher baseline scores for stainable iron in hepatocytes and in portal tract cells than those without. There were significant direct correlations between stainable iron in portal triads and lobular and total Ishak inflammatory and fibrosis scores [P < 0.0001]. Iron in triads at baseline increased risk of outcomes (HR = 1.35, P = 0.02). Stainable iron in hepatocytes decreased, whereas that in portal stromal cells increased significantly [P < 0.0001] over time. Serum iron and TIBC fell significantly over time [P < 0.0001], as did serum ferritin [P = 0.0003]. Chronic PegIFN treatment did not affect stainable iron. HFE genetic variations did not correlate with outcomes, including development of hepatocellular carcinoma.
  
  
  CONCLUSIONS
  Stainable iron in hepatocytes and portal tract cells is a predictor of progression and clinical and histological outcomes in advanced chronic hepatitis C. Chronic low-dose PegIFN therapy did not improve outcomes, nor iron variables.
authors.affiliation: Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Lambrecht
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.forename: Deepa
authors.initials: D
authors.lastname: Naishadham
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stoddard
authors.forename: Thomas
authors.initials: T
authors.lastname: Rogers
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011168:Portal System / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D007501:Iron; C100416:peginterferon alfa-2a