Melania Manco1, Anna Alisi2, Jose-Manuel Fernandez Real3, Francesco Equitani4, Rita DeVito2, Luca Valenti5, Valerio Nobili2. 1. Laboratorio di Malattie Epatiche Auto-Immuni e Metaboliche, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy. Electronic address: melania.manco@opbg.net. 2. Laboratorio di Malattie Epatiche Auto-Immuni e Metaboliche, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy. 3. Section of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona and CIBER Fisiopatología de la Obesidad y Nutrición, Girona, Spain. 4. Unità di Medicina Trasfusionale ed Immuno-Ematologia, Ospedale Santa Maria Goretti, Latina, Italy. 5. Dipartimento di Medicina Interna, Università degli Studi di Milano, Ospedale Maggiore "Ca' Granda", IRCCS, Milano, Italy.
Abstract
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Katharina Mörwald; Elmar Aigner; Peter Bergsten; Susanne M Brunner; Anders Forslund; Joel Kullberg; Hakan Ahlström; Hannes Manell; Kirsten Roomp; Sebastian Schütz; Fanni Zsoldos; Wilfried Renner; Dieter Furthner; Katharina Maruszczak; Stephan Zandanell; Daniel Weghuber; Harald Mangge Journal: Front Endocrinol (Lausanne) Date: 2020-06-18 Impact factor: 5.555