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Hepatic iron is the major determinant of serum ferritin in NAFLD patients
Author(s) -
Ryan John D.,
Armitage Andrew E.,
Cobbold Jeremy F.,
Banerjee Rajarshi,
Borsani Oscar,
Dongiovanni Paola,
Neubauer Stefan,
Morovat Reza,
Wang Lai Mun,
Pasricha SantRayn,
Fargion Silvia,
Collier Jane,
Barnes Eleanor,
Drakesmith Hal,
Valenti Luca,
Pavlides Michael
Publication year - 2018
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13513
Subject(s) - hepcidin , ferritin , medicine , cirrhosis , insulin resistance , endocrinology , nonalcoholic fatty liver disease , adiponectin , gastroenterology , inflammation , fatty liver , insulin , disease
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.