title: Serum ferritin concentration predicts hepatic fibrosis better than hepatic iron concentration in human HFE-Haemochromatosis.
abstract: Ferritin is purported to have proinflammatory and profibrogenic effects on hepatic stellate cells. Thus, rather than acting as a passive indicator of hepatic iron concentration (HIC) in haemochromatosis, ferritin may directly influence fibrosis. This study evaluated whether serum ferritin is a better predictor of hepatic fibrosis compared to variables previously associated with increased fibrosis risk in haemochromatosis.
  
  
  
  We identified 291 C282Y HFE-homozygous patients who had undergone liver biopsy for histological fibrosis staging and measurement of HIC. Ordinal logistic regression determined the best model for fibrosis stage not including serum ferritin. Then, serum ferritin was introduced into this model to assess whether the predictive power of the model was significantly increased and to evaluate the effect on other predictors of fibrosis.
  
  
  
  Ordinal logistic regression analyses without serum ferritin demonstrated that log HIC (OR 2.89; P < .001), male gender (OR 2.93; P = .005), alcohol consumption (g/day) (OR 1.01; P = .004), steatosis (OR 2.86; P = .01), arthritis (OR 2.46; P = .01) predicted increasing fibrosis stage (n=217). Addition of serum ferritin in multivariate analysis substantially improved the predictive power of the model (χ2= 37.15; P < .01) and was highly predictive of fibrosis stage (OR 5.44; P < .001). Inclusion of serum ferritin in this model rendered the effects of HIC, gender, alcohol and steatosis to non-significance.
  
  
  
  In haemochromatosis, serum ferritin is a better predictor of fibrosis stage than HIC, gender, steatosis and alcohol. These data support a hypothesis that ferritin may play a role in fibrosis rather than simply acting as a passive indicator of iron storage.
authors.affiliation: Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.|Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.|School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Marnie J
authors.initials: MJ
authors.lastname: Wood
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.|Greenslopes Hospital, The Gallipoli Medical Research Foundation, Brisbane, Queensland, Australia.
authors.forename: Darrell H G
authors.initials: DHG
authors.lastname: Crawford
authors.affiliation: Biostatistics Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Leesa F
authors.identifier: 0000-0002-8921-9265
authors.initials: LF
authors.lastname: Wockner
authors.affiliation: Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.|School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.|Centre for the Advancement of Clinical Research, Royal Brisbane and Women's Hospital and the University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia.
authors.forename: Lawrie W
authors.initials: LW
authors.lastname: Powell
authors.affiliation: Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.|School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Grant A
authors.identifier: 0000-0001-7058-6201
authors.initials: GA
authors.lastname: Ramm
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D001315:Australia; D005234:Fatty Liver / Q000150:complications* / Q000473:pathology; D005260:Female; D005293:Ferritins / Q000097:blood*; D006432:Hemochromatosis / Q000150:complications* / Q000235:genetics; D000071020:Hemochromatosis Protein / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000097:blood; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood* / Q000235:genetics / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D005293:Ferritins; D007501:Iron
keywords: HFE-Haemochromatosis; alcohol; hepatic fibrosis; hepatic iron concentration; serum ferritin