Hepatic iron is the major determinant of serum ferritin in NAFLD patients

John D. Ryan, Andrew E. Armitage, Jeremy F. Cobbold, Rajarshi Banerjee, Oscar Borsani, Paola Dongiovanni, Stefan Neubauer, Reza Morovat, Lai Mun Wang, Sant Rayn Pasricha, Silvia Fargion, Jane Collier, Eleanor Barnes, Hal Drakesmith, Luca Valenti, Michael Pavlides

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Abstract

Background and Aims: Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinaemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinaemia in NAFLD. Methods: Ferritin levels were examined with markers of iron status, inflammation and liver injury across the clinical spectrum of NAFLD using blood, tissue and magnetic resonance (MR) imaging. A separate larger group of NAFLD patients with hepatic iron staining and quantification were used for validation. Results: Serum ferritin correlated closely with the iron regulatory hormone hepcidin, and liver iron levels determined by MR. Furthermore, ferritin levels reflected lower serum adiponectin, a marker of insulin resistance, and liver fat, but not cytokine or CRP levels. Ferritin levels differed according to fibrosis stage, increasing from early to moderate disease, and declining in cirrhosis. A similar pattern was found in the validation cohort of NAFLD patients, where ferritin levels were highest in those with macrophage iron deposition. Multivariate analysis revealed liver iron and hepcidin levels as the major determinants of serum ferritin. Conclusions: While hyperferritinaemia is associated with markers of liver injury and insulin resistance, serum hepcidin and hepatic iron are the strongest predictors of ferritin levels. These findings highlight the role of disordered iron homeostasis in the pathogenesis of NAFLD, suggesting that therapies aimed at correcting iron metabolism may be beneficial.

Original languageEnglish
Pages (from-to)164-173
JournalLiver International
Volume38
Issue number1
DOIs
Publication statusPublished - 2018

Fingerprint

Ferritins
Iron
Liver
Serum
Hepcidins
Insulin Resistance
Fibrosis
Non-alcoholic Fatty Liver Disease
Inflammation
Adiponectin
Wounds and Injuries
Homeostasis
Magnetic Resonance Spectroscopy
Multivariate Analysis
Fats
Macrophages
Magnetic Resonance Imaging
Hormones
Staining and Labeling
Cytokines

Keywords

  • MRI
  • NAFLD
  • Ferritin
  • Hepcidin
  • Liver iron

ASJC Scopus subject areas

  • Hepatology

Cite this

Ryan, J. D., Armitage, A. E., Cobbold, J. F., Banerjee, R., Borsani, O., Dongiovanni, P., ... Pavlides, M. (2018). Hepatic iron is the major determinant of serum ferritin in NAFLD patients. Liver International, 38(1), 164-173. https://doi.org/10.1111/liv.13513

Hepatic iron is the major determinant of serum ferritin in NAFLD patients. / Ryan, John D.; Armitage, Andrew E.; Cobbold, Jeremy F.; Banerjee, Rajarshi; Borsani, Oscar; Dongiovanni, Paola; Neubauer, Stefan; Morovat, Reza; Wang, Lai Mun; Pasricha, Sant Rayn; Fargion, Silvia; Collier, Jane; Barnes, Eleanor; Drakesmith, Hal; Valenti, Luca; Pavlides, Michael.

In: Liver International, Vol. 38, No. 1, 2018, p. 164-173.

Research output: Contribution to journalArticle

Ryan, JD, Armitage, AE, Cobbold, JF, Banerjee, R, Borsani, O, Dongiovanni, P, Neubauer, S, Morovat, R, Wang, LM, Pasricha, SR, Fargion, S, Collier, J, Barnes, E, Drakesmith, H, Valenti, L & Pavlides, M 2018, 'Hepatic iron is the major determinant of serum ferritin in NAFLD patients', Liver International, vol. 38, no. 1, pp. 164-173. https://doi.org/10.1111/liv.13513
Ryan, John D. ; Armitage, Andrew E. ; Cobbold, Jeremy F. ; Banerjee, Rajarshi ; Borsani, Oscar ; Dongiovanni, Paola ; Neubauer, Stefan ; Morovat, Reza ; Wang, Lai Mun ; Pasricha, Sant Rayn ; Fargion, Silvia ; Collier, Jane ; Barnes, Eleanor ; Drakesmith, Hal ; Valenti, Luca ; Pavlides, Michael. / Hepatic iron is the major determinant of serum ferritin in NAFLD patients. In: Liver International. 2018 ; Vol. 38, No. 1. pp. 164-173.
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abstract = "Background and Aims: Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinaemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinaemia in NAFLD. Methods: Ferritin levels were examined with markers of iron status, inflammation and liver injury across the clinical spectrum of NAFLD using blood, tissue and magnetic resonance (MR) imaging. A separate larger group of NAFLD patients with hepatic iron staining and quantification were used for validation. Results: Serum ferritin correlated closely with the iron regulatory hormone hepcidin, and liver iron levels determined by MR. Furthermore, ferritin levels reflected lower serum adiponectin, a marker of insulin resistance, and liver fat, but not cytokine or CRP levels. Ferritin levels differed according to fibrosis stage, increasing from early to moderate disease, and declining in cirrhosis. A similar pattern was found in the validation cohort of NAFLD patients, where ferritin levels were highest in those with macrophage iron deposition. Multivariate analysis revealed liver iron and hepcidin levels as the major determinants of serum ferritin. Conclusions: While hyperferritinaemia is associated with markers of liver injury and insulin resistance, serum hepcidin and hepatic iron are the strongest predictors of ferritin levels. These findings highlight the role of disordered iron homeostasis in the pathogenesis of NAFLD, suggesting that therapies aimed at correcting iron metabolism may be beneficial.",
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T1 - Hepatic iron is the major determinant of serum ferritin in NAFLD patients

AU - Ryan, John D.

AU - Armitage, Andrew E.

AU - Cobbold, Jeremy F.

AU - Banerjee, Rajarshi

AU - Borsani, Oscar

AU - Dongiovanni, Paola

AU - Neubauer, Stefan

AU - Morovat, Reza

AU - Wang, Lai Mun

AU - Pasricha, Sant Rayn

AU - Fargion, Silvia

AU - Collier, Jane

AU - Barnes, Eleanor

AU - Drakesmith, Hal

AU - Valenti, Luca

AU - Pavlides, Michael

PY - 2018

Y1 - 2018

N2 - Background and Aims: Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinaemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinaemia in NAFLD. Methods: Ferritin levels were examined with markers of iron status, inflammation and liver injury across the clinical spectrum of NAFLD using blood, tissue and magnetic resonance (MR) imaging. A separate larger group of NAFLD patients with hepatic iron staining and quantification were used for validation. Results: Serum ferritin correlated closely with the iron regulatory hormone hepcidin, and liver iron levels determined by MR. Furthermore, ferritin levels reflected lower serum adiponectin, a marker of insulin resistance, and liver fat, but not cytokine or CRP levels. Ferritin levels differed according to fibrosis stage, increasing from early to moderate disease, and declining in cirrhosis. A similar pattern was found in the validation cohort of NAFLD patients, where ferritin levels were highest in those with macrophage iron deposition. Multivariate analysis revealed liver iron and hepcidin levels as the major determinants of serum ferritin. Conclusions: While hyperferritinaemia is associated with markers of liver injury and insulin resistance, serum hepcidin and hepatic iron are the strongest predictors of ferritin levels. These findings highlight the role of disordered iron homeostasis in the pathogenesis of NAFLD, suggesting that therapies aimed at correcting iron metabolism may be beneficial.

AB - Background and Aims: Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinaemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinaemia in NAFLD. Methods: Ferritin levels were examined with markers of iron status, inflammation and liver injury across the clinical spectrum of NAFLD using blood, tissue and magnetic resonance (MR) imaging. A separate larger group of NAFLD patients with hepatic iron staining and quantification were used for validation. Results: Serum ferritin correlated closely with the iron regulatory hormone hepcidin, and liver iron levels determined by MR. Furthermore, ferritin levels reflected lower serum adiponectin, a marker of insulin resistance, and liver fat, but not cytokine or CRP levels. Ferritin levels differed according to fibrosis stage, increasing from early to moderate disease, and declining in cirrhosis. A similar pattern was found in the validation cohort of NAFLD patients, where ferritin levels were highest in those with macrophage iron deposition. Multivariate analysis revealed liver iron and hepcidin levels as the major determinants of serum ferritin. Conclusions: While hyperferritinaemia is associated with markers of liver injury and insulin resistance, serum hepcidin and hepatic iron are the strongest predictors of ferritin levels. These findings highlight the role of disordered iron homeostasis in the pathogenesis of NAFLD, suggesting that therapies aimed at correcting iron metabolism may be beneficial.

KW - MRI

KW - NAFLD

KW - Ferritin

KW - Hepcidin

KW - Liver iron

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