Extrahepatic Iron Loading Associates With the Propensity to Develop Advanced Hepatic Fibrosis in Hemochromatosis

John K. Olynyk; Timothy G. St. Pierre; James Chen; David M. Frazer; Louise E. Ramm; Grant A. Ramm

Gastro Hep Advances (Jan 2024)

Extrahepatic Iron Loading Associates With the Propensity to Develop Advanced Hepatic Fibrosis in Hemochromatosis

John K. Olynyk,
Timothy G. St. Pierre,
James Chen,
David M. Frazer,
Louise E. Ramm,
Grant A. Ramm

Affiliations

John K. Olynyk: Curtin Medical School, Curtin University, Bentley, Western Australia, Australia; Department of Gastroenterology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia; Correspondence: Address correspondence to: John K. Olynyk, MD, Curtin Medical School, Curtin University, Kent St., Bentley 6102, Western Australia, Australia.
Timothy G. St. Pierre: School of Physics, Mathematics, and Computing, University of Western Australia, Crawley, Western Australia, Australia
James Chen: Department of Gastroenterology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
David M. Frazer: Molecular Nutrition Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; School of Biomedical Sciences, Queensland University of Technology, Gardens Point, Queensland, Australia; School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia
Louise E. Ramm: Molecular Nutrition Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
Grant A. Ramm: Molecular Nutrition Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; Faculty of Medicine, The University of Queensland, Herston, Queensland, Australia

Journal volume & issue: Vol. 3, no. 4
pp. 454 – 460

Abstract

Read online

Background and Aims: Hemostatic iron regulator-hemochromatosis can result in progressive iron-loading and advanced hepatic fibrosis in some individuals. We studied total body and hepatic iron loading to determine whether the distribution of iron-loading influences the risk of advanced fibrosis. Methods: One hundred thirty-eight men and 66 women with hemochromatosis who underwent liver biopsy for staging of hepatic fibrosis had evaluation of hepatic iron concentration (HIC), hepatic iron index (HIC/age), total body iron stores (mobilizable iron), and mobilizable iron/HIC ratio (a marker of total body iron relative to hepatic iron). The potential impact of liver volume on mobilizable iron stores was assessed using magnetic resonance imaging in a separate cohort of 19 newly diagnosed individuals with hemochromatosis. Results: Of 204 biopsied subjects, 41 had advanced fibrosis and exhibited 60% greater accumulation of mobilizable iron relative to HIC (mean 0.070 ± 0.008 g Fe/[μmol Fe/g]) compared with 163 subjects with low-grade fibrosis (mean 0.044 ± 0.002 g Fe/[μmol Fe/g], P < .0001). Linear regression modeling confirmed a discrete advanced hepatic fibrosis phenotype associated with greater mobilizable iron stores relative to HIC. The ratios of the upper to lower 95% limits of the distributions of liver volumes and the mobilizable iron/HIC ratios were 2.7 (95% confidence interval 2.3–3.0) and 9.7 (95% confidence interval 8.0–11.7), respectively, indicating that the distribution of liver volumes is not sufficiently wide to explain the variability in mobilizable iron/HIC ratios, suggesting that significant extrahepatic iron loading is present in those with advanced hepatic fibrosis. Conclusion: Advanced hepatic fibrosis develops in hemostatic iron regulator-hemochromatosis individuals who also have excessive extrahepatic mobilizable iron stores.

Published in Gastro Hep Advances

ISSN: 2772-5723 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.sciencedirect.com/journal/gastro-hep-advances

About the journal

Abstract

Keywords