非酒精性脂肪性肝病患者血清铁代谢指标的变化及临床意义

目的观察非酒精性脂肪性肝病(NAFLD)患者血清铁代谢指标变化及其临床意义。方法收集2014年7月-2016年4月上海市第八人民医院收治的68例NAFLD患者(NAFLD组),另选取健康体检者70例(健康对照组)。68例NAFLD患者中单纯NAFLD患者24例,伴ALT异常者44例。检测所有研究对象的AST、ALT、TC、TG水平及铁代谢指标[血清铁(SI)、血清铁蛋白(SF)、血清铁调素(HEPC)]水平,观察NAFLD患者ALT异常与血清铁代谢指标的相关性。计量资料组间比较采用独立样本t检验,计数资料组间比较采用χ~2检验,两变量间的相关性采用Pearson相关系数分析。结果 NAFLD组患者的BMI、ALT、AST、TC、TG水平均显著高于健康对照组(t值分别为9.8、8.6、8.5、9.2、2.7,P值均0.05);铁代谢指标SI、SF水平显著高于健康对照组[SI:(21.7±7.1)μmol/L vs(18.7±6.9)μmol/L,t=2.3,P=0.02;SF:(340.2±257.6)μg/L vs(119.1±81.2)μg/L,t=6.7,P0.01)],HEPC显著低于健康对照组[(12.2±5.3)μg/L vs(22.2±6.5)μg/L,t=9.9,P0.01)]。伴ALT异常NAFLD患者的血清ALT、SI、SF水平显著高于单纯NAFLD患者[ALT:(89±58)U/L vs(26±8)U/L,t=7.1,P0.01;SI:(23.4±6.2)μmol/L vs(19.6±7.9)μmol/L,t=2.2,P=0.03;SF:(406.2±290.0)μg/L vs(219.4±112.0)μg/L,t=3.7,P0.01),血清HEPC水平显著低于单纯NAFLD患者[(7.4±4.9)μg/L vs(16.1±7.8)μg/L,t=4.7,P0.01)]。Pearson相关性分析结果显示,SF与ALT、AST呈显著正相关(r值分别为0.28、0.34,P值分别为0.02、0.01)。结论 NAFLD患者存在显著铁超载,且在伴ALT异常的NAFLD患者中表现更为明显。SF与ALT、AST呈显著正相关。血清铁蛋白能在一定程度上反映NAFLD患者肝损伤严重程度。     

铁超负荷性心肌病的认识与进展

铁超负荷性心肌病在临床中较常见且病死率高,是原发性血色病和继发性铁超负荷疾病的主要死亡原因之一。由于早期症状缺乏特异性,铁超负荷性心肌病常被忽视,以至后期治疗效果差。随着心脏磁共振等技术的应用和发展,以及心肌细胞摄取铁离子机制研究的深入,铁超负荷性心肌病的早期诊断及治疗取得满意的效果。现就铁超负荷性心肌病的目前认识和研究进展进行综述。     

MRI评价肝脏铁过载的应用进展

许多研究表明,肝脏铁过载与肝炎、肝纤维化、肝硬化及肿瘤具有密切关系.目前检测铁过载的方法,如血浆铁蛋白检测、肝脏穿刺活检以及无创检查超导量子干涉仪等均具有一定的局限性,磁共振检查技术(magneticresonanceimaging,MRI)是目前公认的,能够无创、安全、准确的检查肝脏铁含量的方法.本文对肝脏铁过载及MRI在肝脏铁过载中的应用进展进行综述.     

铁过载检测与祛铁治疗

临床上对于低危骨髓增生异常综合征(myelodysplastic syndromes,MDS)、再生障碍性贫血(aplastic anemia,AA)以及β珠蛋白生成障碍性贫血等疾病的患者来说,输血治疗是挽救其生命和     

铁死亡治疗肝脏疾病的新机会

铁死亡是由Dixon于2012年发现的一种新型的细胞死亡形式,其有异于目前发现的其他细胞死亡方式,并犹如一把双刃剑在不同疾病层面发挥着不同的生物学效应。越来越多研究表明,铁死亡发生在各类急慢性肝病的发病、转归、预后等各个方面,所以了解铁死亡有利于明晰更多肝脏疾病的发病机制,而靶向调控铁死亡将有望成为治疗各类肝脏疾病的奠基石。我们通过查阅中外文献数据库,概述铁死亡独特的细胞死亡机制及其相关影响信号和通路,并介绍在各类急慢性肝病中铁死亡可能性的切入机制和靶点,为铁死亡在肝脏疾病中的应用和研究提供科学依据。     

铁螯合剂类抗疟药的研究进展

疟疾是危害人类健康的重要寄生虫病。据统计,全球约有40%人口受到威胁,每年发病人数为2·5~3亿,其中死亡人数约200万。对多种抗疟药具有抗性的恶性疟原虫正迅速扩散。因此,研制并开发新型抗疟药对控制全球疟疾具有重大意义。铁螯合剂作为一种新型抗疟化合物,近年来备受关注。     

铁过载对成骨细胞铁稳态及生物活性的影响

目的了解铁过载对成骨细胞铁稳态及生物活性的影响。方法 34℃条件下体外培养人成骨细胞(hFOB1.19),以不同浓度(50、100、200μmol/L)枸橼酸铁铵(FAC)干预,用RT-PCR检测成骨细胞铁调节基因膜转铁蛋白(FPN1)、转铁蛋白受体(TfR)和二价金属转运蛋白1(DMT1)表达的变化;用激光共聚焦扫描显微镜(CLSM)观察成骨细胞铁离子荧光强度;流式细胞仪检测成骨细胞活性氧(ROS)水平;碱性磷酸酶活性试剂盒检测碱性磷酸酶活性;Vonkossa染色法行钙结节染色。结果与对照组相比,FAC干预48h后FPN1mRNA的表达随FAC干预浓度增加呈剂量依赖性上调,TfR、DMT1mRNA的表达呈剂量依赖性下调(P0.05);FAC干预48h后成骨细胞铁离子荧光强度剂量依赖性减弱,与对照组相比差异有统计学意义(P0.05);48h后成骨细胞ROS水平随FAC干预浓度增加呈剂量依赖性升高(P0.05);FAC干预10d后各组成骨细胞碱性磷酸酶活性均随FAC浓度增高而降低,差异有统计学意义(P0.05);与对照组相比,FAC干预17d后成骨细胞钙结节染色显示矿化面积和钙结节形成随FAC浓度增加而减少。结论铁过载对成骨细胞生物活性有明显抑制作用,其机制可能与细胞内铁离子浓度增加及活性氧水平升高有关。     

慢性丙型肝炎铁代谢的失调机制

肝脏是人体储存铁离子的主要器官,因此铁离子代谢失常与慢性肝炎密切相关。目前,慢性丙型肝炎(CHC)中铁离子过载的机制并没有完全阐明。铁调素调控非常复杂,依赖于许多变量,包括不同阶段的肝脏炎症情况、转铁蛋白参与的铁离子循环以及胞内铁离子储存等,这些因素都与引起HCV相关肝脏疾病患者中铁离子浓度的变化有关。讨论了系统铁离子稳态的调控、CHC与铁离子失调的关系及诱发CHC铁离子过载的机制。认为深入认识铁离子稳态和相关信号通路之间的关系将促进HCV相关疾病的控制与治疗。     

铁过载及铁死亡与代谢相关脂肪性肝病的研究进展

铁作为机体必须的微量元素,对维持机体健康至关重要。过多的铁离子可促进活性氧的产生,从而对细胞、组织造成损伤。随着铁死亡这一铁依赖性的细胞死亡方式概念的提出,越来越多的研究聚焦到铁死亡。近年来的研究证实了铁过载及铁死亡与代谢性疾病之间的关系,为代谢相关脂肪性肝病等疾病的防治带来了曙光。该文就国内外铁过载及铁死亡与代谢相关...     

Hepcidin response to acute iron intake and chronic iron loading in dysmetabolic iron overload syndrome

Background: The pathogenesis of dysmetabolic iron overload syndrome (DIOS) is still unclear. Hepcidin is the key regulator of iron homeostasis controlling iron absorption and macrophage release. Aim: To investigate hepcidin regulation by iron in DIOS. Methods: We analysed urinary hepcidin at baseline and 24 h after a 65 mg oral iron dose in 24 patients at diagnosis and after iron depletion (n=13) and compared data with those previously observed in 23 healthy controls. Serum iron indices, liver histology and metabolic data were available for all patients. Results: At diagnosis, hepcidin values were significantly higher than in controls (P<0.001). After iron depletion, hepcidin levels decreased to normal values in all patients. At baseline, a significant response of hepcidin to iron challenge was observed only in the subgroup with lower basal hepcidin concentration (P=0.007). In iron‐depleted patients, urinary hepcidin significantly increased after oral iron test (P=0.006). Conclusions: Ours findings suggest that in DIOS, the progression of iron accumulation is counteracted by the increase in hepcidin production and progressive reduction of iron absorption, explaining why these patients develop a mild–moderate iron overload that tends to a plateau.     

Therapeutic phlebotomy is safe in children with sickle cell anaemia and can be effective treatment for transfusional iron overload

Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (?8·7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained unchanged. Therapeutic phlebotomy was safe and well‐tolerated, with net iron removal in most children who completed 30 months of protocol‐directed treatment.     

Non-invasive assessment of tissue iron overload in the liver by magnetic resonance imaging

Summary. We investigated the clinical usefulness of a standard magnetic resonance imaging (MRI) system for non-invasive determination of the liver iron concentration in 38 patients with iron overload and 15 normal controls by measurement of the signal intensity ratio between liver and skeletal muscle (SIR). However, SIR was found dependent on the applied repetition time (TR) of the MRI system, which led us to investigate this relationship in autopsy material of liver and muscle tissue specimens with various iron content. Based on these results, adjustment of SIR measurements to a constant value of TR was achieved. By use of this technique we found a close correlation between MRI and chemically determined liver iron concentration ( r ²= 0.98) as well as the serum ferritin concentration ( r ²= 0.86). The reproducibility was sufficiently good for the use of MRI in the follow-up of iron reductive treatment. The use of iron store parameters in serum was found insufficient as indicators of endpoint for venesection therapy, if 20 μmol Fe/g dry weight was applied as the upper reference limit of the liver iron concentration.
It is concluded that MRI based on SIR measurements offers a precise and reproducible non-invasive method for the determination and follow-up of iron overload within a wide range of liver iron concentrations. Our findings may increase the clinical use of MRI in haematological patients with iron overload.     

Dose-related effects of dietary iron supplementation in producing hepatic iron overload in rats

The influence of varying the level of supplemental dietary iron on the development of hepatic iron overload was examined in rats. Two days after giving birth, Porton rats were fed a diet supplemented with 0, 0.5, 1 or 2% carbonyl iron, to institute dietary iron supplementation to the young via breast milk. After weaning, the offspring continued to receive the assigned diet until 32 weeks of age. Liver biopsies were taken from some rats at 8, 16 and 24 weeks of age and from all rats at 32 weeks of age, for assessment of iron overload. For both male and female rats, hepatic iron content was increased in a dose-related manner by feeding supplemented diet. Hepatic iron content of male rats tended to reach a plateau after 8–16 weeks of supplementation, while that of female rats continued to rise throughout the experimental period, such that the hepatic iron content of female rats was 2.8-fold that of similarly treated males at 32 weeks of age. Iron supplementation was associated with only moderate retardation of growth. By choosing an appropriate level of iron supplementation, good (grade III-IV) hepatic iron loading can be achieved with minimal adverse effects on the animals’ overall health.     

HFE gene in primary and secondary hepatic iron overload

Distinct from hereditary haemochromatosis, hepatic iron overload is a common finding in several chronic liver diseases. Many studies have investigated the prevalence, distribution and possible contributory role of excess hepatic iron in non-haemochromatotic chronic liver diseases. Indeed, some authors have proposed iron removal in liver diseases other than hereditary haemochromatosis. However, the pathogenesis of secondary iron overload remains unclear. The High Fe (HFE) gene has been implicated, but the reported data are controversial. In this article, we summarise current concepts regarding the cellular role of the HFE protein in iron homeostasis. We review the current status of the literature regarding the prevalence, hepatic distribution and possible therapeutic implications of iron overload in chronic hepatitis C, hepatitis B, alcoholic and nonalcoholic fatty liver diseases and porphyria cutanea tarda.We discuss the evidence regarding the role of HFE gene mutations in these liver diseases. Finally, we summarize the common and specific features of iron overload in liver diseases other than haemochromatosis.     

Association between hepatic iron overload assessed by magnetic resonance imaging and glucose intolerance states in the general population

Background and aimWhile there is evidence that iron overload disorders are associated with type 2 diabetes, the relationship between hepatic iron overload and prediabetes remains unclear. We aimed to investigate the association between hepatic iron overload, as assessed by magnetic resonance imaging (MRI), and different glucose intolerance states in the population-based Study.Methods and resultsWe included data from 1622 individuals with MRI data, who did not have known type 2 diabetes (T2DM). Using an oral glucose tolerance testing, participants were classified as having isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) or previously unknown T2DM. Hepatic iron and fat contents were assessed through quantitative MRI. We undertook linear and multinomial logistic regression models adjusted for potential confounders and MRI-assessed hepatic fat content to examine the association of hepatic iron overload with different glucose intolerance states or continuous markers of glucose metabolism.MRI-assessed hepatic iron overload was positively associated only with both 2-h plasma glucose (β = 0.32; 95%CI 0.04–0.60) and the combined IFG + IGT category (relative risk ratio = 1.87; 95%CI 1.15–3.06). No significant associations were found between hepatic iron overload and other glucose intolerance states or biomarkers of glucose metabolism, independently of potential confounders.ConclusionsMRI-assessed hepatic iron overload was associated with higher 2-h glucose concentrations and the combined IFG + IGT category, but not with other glucose intolerance states. Our findings suggest a weak adverse impact of hepatic iron overload on glucose metabolism, but further studies are needed to confirm these findings.     

Overview of guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload

Between 2002 and 2008, a number of consensus statements and guidelines were developed by various groups around the world to educate healthcare professionals on the treatment of myelodysplastic syndromes (MDS), including the management of transfusional iron overload with iron chelation therapy. Guidelines have been developed by The Italian Society of Hematology, The UK MDS Guidelines Group, The Nagasaki Group, The National Comprehensive Cancer Network, and The MDS Foundation. These guidelines show that the approaches to managing iron overload in patients with MDS are region specific, differing in their recommendations for when iron chelation therapy should be initiated and strategies for the ongoing management of iron overload. The guidelines all agree that red blood cell transfusions are clinically beneficial to treat the symptomatic anemia in MDS, and that patients with low-risk MDS receiving transfusions are the most likely to benefit from iron chelation therapy.