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J Hepatol. 2011 Sep;55(3):647-653. doi: 10.1016/j.jhep.2010.12.007. Epub 2010 Dec 17.

Early interplay of intra-hepatic iron and insulin resistance in children with non-alcoholic fatty liver disease.

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Laboratorio di Malattie Epatiche Auto-Immuni e Metaboliche, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy. Electronic address:
Laboratorio di Malattie Epatiche Auto-Immuni e Metaboliche, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy.
Section of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona and CIBER Fisiopatología de la Obesidad y Nutrición, Girona, Spain.
Unità di Medicina Trasfusionale ed Immuno-Ematologia, Ospedale Santa Maria Goretti, Latina, Italy.
Dipartimento di Medicina Interna, Università degli Studi di Milano, Ospedale Maggiore "Ca' Granda", IRCCS, Milano, Italy.



The liver is a crucial organ at the crossroads of iron and glucose metabolism. The aim of the study was to assess intra-hepatic iron in young patients with non-alcoholic fatty liver disease (NAFLD) and its association with insulin resistance and severity of liver damage.


Intrahepatic iron content was assessed (Pearl's stain grade) in 66 patients (41 males, age 3.3-17.6years) with biopsy-proven NAFLD. Mutations of the Hereditary Hemochromatosis (HFE) gene were determined by sequence allele-specific polymerase chain reaction. Insulin resistance was estimated by means of the Oral Glucose Tolerance Test and the Insulin Sensitivity Index (ISI); the Insulino-Genic Index was also calculated. Tumor necrosis factor-alpha and interleukin-6 were measured.


Low-mild intra-hepatic iron deposition was observed in one out of five children (n=15, 22%), and it was not associated with HFE mutations, carried by 17 patients (26%). Among carriers of HFE mutations, four had siderosis. No abnormalities were observed in systemic indices of iron balance. Serum ferritin was within normal adult ranges in all patients (33.6±7.6ng/ml), but it was correlated with ISI (r(o)=-0.361; p=0.003). No significant difference was observed in insulin sensitivity, iron balance, inflammatory milieu, and liver histology between patients with and without hepatic siderosis.


In young obese individuals with NAFLD, despite normal peripheral iron parameters, mild intra-hepatic iron deposition is a frequent finding, but it is not associated with insulin resistance or severity of liver damage. Longitudinal studies are required to define the long-term relevance of these findings.

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