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Consensus Statement on the definition and classification of metabolic hyperferritinaemia

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Version 1 2023-03-23, 14:46
journal contribution
posted on 2023-03-23, 14:46 authored by Luca Valenti, Elena Corradini, Leon A Adams, Elmar Aigner, Saleh Alqahtani, Marco Arrese, Edouard Bardou-Jacquet, Elisabetta Bugianesi, Jose-Manuel Fernandez-Real, Domenico Girelli, Hannes Hagström, Benjamin Henninger, Kris Kowdley, Guido Ligabue, Donald McClain, Fabrice Lainé, Koji Miyanishi, Martina U Muckenthaler, Alessia Pagani, Patrizia Pedrotti, Antonello Pietrangelo, Daniele Prati, John RyanJohn Ryan, Laura Silvestri, C Wendy Spearman, Per Stål, Emmanuel A Tsochatzis, Francesca Vinchi, Ming-Hua Zheng, Heinz Zoller

Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes. 

Funding

Ministero della Salute, Ricerca Finalizzata RF-2016-02364358, RC Rete cardiologica ‘CV PREVITAL’

Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico ‘Liver BIBLE’ (PR-0391)

Innovative Medicines Initiative 2 joint undertaking of European Union’s Horizon 2020 research and innovation programme

EFPIA European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS, H2020 under grant agreement ‘101016726’

European Union, programme ‘Photonics’ under grant agreement ‘101016726’

Fondo Nacional de Ciencia y Tecnología de Chile (FONDECYT #1191145)

Agencia Nacional de Investigación y Desarrollo

ANID ACE 210009 grant NIH (P30DK124723)

Veterans Administration (2I01 BX001140) SFB1036, SFB1118 and DFG (FerrOs — FOR5146; SPP2306)

Marsilius Kolleg

National Natural Science Foundation of China (82070588)

High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032)

Swedish Cancer Society (170690)

Stockholm County Council (K2017-4579)

History

Comments

The original article is available at https://www.nature.com/

Published Citation

Valenti L. et al. Consensus statement on the definition and classification of metabolic hyperferritinaemia. Nat Rev Endocrinol. 2023;19(5):299-310.

Publication Date

17 February 2023

PubMed ID

36805052

Department/Unit

  • Beaumont Hospital
  • Medicine

Publisher

Nature Pub. Group

Version

  • Accepted Version (Postprint)