Laboratorio di Malattie Epatiche Auto-Immuni e Metaboliche, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy.
Laboratorio di Malattie Epatiche Auto-Immuni e Metaboliche, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy.
J Hepatol. 2011 Sep;55(3):647-653. doi: 10.1016/j.jhep.2010.12.007. Epub 2010 Dec 17.
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.
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.
肝脏是铁和葡萄糖代谢交汇的关键器官。本研究旨在评估非酒精性脂肪性肝病（NAFLD）年轻患者肝内铁含量及其与胰岛素抵抗和肝损伤严重程度的关系。
对 66 例经肝活检证实的 NAFLD 患者（男 41 例，年龄 3.3-17.6 岁）进行肝内铁含量评估（Pearl 染色分级）。采用序列等位基因特异性聚合酶链反应检测遗传性血色病（HFE）基因突变。采用口服葡萄糖耐量试验和胰岛素敏感性指数（ISI）评估胰岛素抵抗；还计算了胰岛素生成指数。测定肿瘤坏死因子-α和白细胞介素-6。
五分之一的儿童（n=15，22%）存在轻度肝内铁沉积，但与 HFE 突变无关，17 例（26%）患者携带 HFE 突变。在 HFE 突变携带者中，有 4 例发生血色病。未观察到铁平衡的系统指标异常。所有患者的血清铁蛋白均在正常成人范围内（33.6±7.6ng/ml），但与 ISI 呈负相关（r(o)=-0.361；p=0.003）。肝内铁沉积患者与无肝内铁沉积患者的胰岛素敏感性、铁平衡、炎症环境和肝组织学无显著差异。
在患有 NAFLD 的肥胖年轻个体中，尽管外周铁参数正常，但仍存在轻度肝内铁沉积，但其与胰岛素抵抗或肝损伤严重程度无关。需要进行纵向研究来确定这些发现的长期意义。
