BACKGROUND Perturbations in iron homeostasis have been reported to be associated with irreversible liver injury in chronic liver disease (CLD). However, it is not clear whether liver dysfunction per se underlies such dysregulation or whether other factors also contribute to it. This study attempted to examine the issues involved. METHODS Patients diagnosed to have chronic liver disease (n = 63), who underwent a medically-indicated upper gastrointestinal endoscopy, were the subjects of this study. Patients with dyspepsia, who underwent such a procedure, and were found to have no endoscopic abnormalities, were used as control subjects (n = 49). Duodenal mucosal samples were obtained to study mRNA and protein levels of duodenal proteins involved in iron absorption. A blood sample was also obtained for estimation of hematological, iron-related, inflammatory and liver function-related parameters. RESULTS Patients with CLD had impaired liver function, anemia of inflammation and lower serum levels of hepcidin than control subjects. Gene (mRNA) expression levels of duodenal ferroportin and duodenal cytochrome b (proteins involved in iron absorption) were decreased, while that of divalent metal transporter-1 (DMT-1) was unchanged. Protein expression of DMT-1 was, however, decreased while that of ferroportin was unchanged. In the CLD group, serum hepcidin was predicted independently by serum ferritin and hemoglobin, but not by C-reactive protein (a marker of inflammation). CLD patients with serum ferritin greater than 300 μg/dL had significantly greater liver dysfunction (as indicated by significantly higher serum concentrations of bilirubin, AST and ALT, and MELD scores), higher serum concentrations of CRP and hepcidin, and higher ferroportin protein expression, than those with serum ferritin ≤ 300 μg/dL. CONCLUSIONS In patients with CLD, anemia of inflammation and low serum hepcidin levels were found to paradoxically co-exist. Expression of duodenal proteins involved in iron absorption were either decreased or unaltered in these patients. The hepcidin response to higher body iron levels and/or inflammation appeared to be functional in these patients, despite the presence of liver disease.

中文翻译：

---

在慢性肝病中，铁稳态失调，但铁-铁调素轴功能正常。

背景技术据报道，铁稳态的扰动与慢性肝病（CLD）中不可逆的肝损伤有关。但是，尚不清楚肝功能障碍本身是否是这种功能失调的基础，还是其他因素也导致了这种功能失调。这项研究试图检查所涉及的问题。方法本研究的对象是经诊断为慢性肝病的患者（n = 63），他们接受了医学上的上消化道内镜检查。接受了此类手术且没有内镜异常的消化不良患者被用作对照组（n = 49）。获得十二指肠粘膜样品以研究参与铁吸收的十二指肠蛋白质的mRNA和蛋白质水平。还获得了血液样本，用于评估血液学，铁相关，炎症和肝功能相关参数。结果CLD患者的肝功能受损，炎症性贫血和铁调素的血清水平低于对照组。十二指肠铁转运蛋白和十二指肠细胞色素b（参与铁吸收的蛋白质）的基因（mRNA）表达水平降低，而二价金属转运蛋白-1（DMT-1）的基因表达水平不变。但是，DMT-1的蛋白表达下降，而铁转运蛋白的蛋白表达未改变。在CLD组中，血清铁调素是通过血清铁蛋白和血红蛋白独立预测的，而不是通过C反应蛋白（炎症的标志物）预测的。血清铁蛋白大于300μg/ dL的CLD患者的肝功能异常显着加剧（血清胆红素，AST和ALT的血清浓度明显升高，以及MELD评分表明），与血清铁蛋白≤300μg/ dL的患者相比，血清CRP和铁调素的浓度更高，铁转运蛋白的蛋白表达更高。结论在CLD患者中，发现炎症性贫血和血清Hepcidin水平低下是矛盾的并存。这些患者中参与铁吸收的十二指肠蛋白的表达降低或未改变。尽管存在肝脏疾病，这些患者对高铁水平和/或炎症的铁调素反应似乎仍然起作用。这些患者中参与铁吸收的十二指肠蛋白的表达降低或未改变。尽管存在肝脏疾病，这些患者对高铁水平和/或炎症的铁调素反应似乎仍然起作用。这些患者中参与铁吸收的十二指肠蛋白的表达降低或未改变。尽管存在肝脏疾病，这些患者对高铁水平和/或炎症的铁调素反应似乎仍然起作用。