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.     

去铁胺治疗骨髓增生异常综合征及再生障碍性贫血患者输血依赖性铁过载的临床观察

近年来,对于骨髓增生异常综合征(MDS)及再生障碍性贫血(AA)等患者由于长期反复输血导致输血依赖性铁过载已越来越受到国内外学者的广泛关注。体内的铁过量沉积于心脏、肝脏及内分泌系统,会引起心功能衰竭、心律失常、肝纤维化、糖尿病等并发症,从而影响患者的生存期及生存质量。我们通过对10例应用去铁胺治疗的MDS及AA患者的临床观察,进一步探讨输血依赖性铁过载的机制及祛铁治疗。     

MRI用于肝多房棘球蚴病铁沉积评估的初步研究

目的　探索MRI联合血清铁蛋白用于肝多房棘球蚴病患者肝脏铁沉积评估的效果。方法　对96例肝多房棘球蚴病确诊患者和30例健康志愿者行常规1.5T 磁共振扫描,并采集相关实验室检查资料,分析肝脏/肌肉信号强度比、血清铁蛋白水平、肝功能指标及其相关性等。结果　肝多房棘球蚴病患者与健康志愿者肝脏/肌肉信号强度比分别为（1.95 ± 0.57）和（2.22 ± 0.28）,差异有统计学意义（t = 2.022,P < 0.05）,且肝多房棘球蚴病患者肝脏/肌肉信号强度比与血清铁蛋白水平呈中度负相关( rs = –0.446,P < 0.01)。 结论　肝多房棘球蚴病患者肝脏内多存在异常铁沉积,而血清铁蛋白检测可辅助判断肝多房棘球蚴病患者肝脏内异常铁沉积。MRI测量的肝脏/肌肉信号强度比可作为无创性评估肝多房棘球蚴病患者肝脏铁沉积的一种方法。     

规律去铁治疗骨髓增生异常综合征患者输血依赖性铁过载的临床分析

目的 探讨骨髓增生异常综合征(MDS)患者铁代谢状况及去铁治疗后患者各器官功能的变化.方法 通过检测去铁胺治疗前及治疗后MDS患者体内血清铁蛋白、肝脏谷丙转氨酶(ALT)、谷草转氨酶(AST)、肝脏CT值、彩超检查心脏大小及射血分数,比较去铁治疗前后患者血清铁蛋白变化及各器官功能变化情况.结果 去铁治疗前患者血清铁蛋白浓度、ALT、AST、肝脏CT值均比去铁治疗后高,差异有统计学意义(P＜0.05);心脏超声检查结果显示,1例患者治疗前有心脏扩大,射血分数降低,治疗2个月后心脏回缩,射血分数增高.结论 MDS患者存在不同程度的铁过载,通过去铁治疗后,患者血清铁蛋白、肝功能、心功能有不同程度恢复,提示长期输血可导致铁过载,从而诱发心脏、肝脏等器官损害甚至死亡.早期重视易导致铁过载疾病的铁负荷情况,并予以足够长的疗程,可使受损的器官功能尽可能恢复正常.     

铁过载对器官功能损伤及磁共振检测铁过载研究进展

铁过载可导致多器官功能损害。铁过载的病情隐匿,表现多样,进展缓慢,组织受累程度多变,常在组织和器官显著受损后才能作出诊断。及时进行铁螯合治疗能有效减轻损害程度。因此,及时检测器官铁过载至关重要。目前检测铁含量的指标包括肝活检检测肝铁浓度(liver iron concentration,LIC)、血清铁蛋白(serum ferritin,SF)和转铁蛋白饱和度(transferrin saturation,TS)及核磁共振成像(MRI)。由于MRI检测器官的无创性及可靠性,该技术越来越受到学者的重视。本文就铁过载引起各个器官的损害情况及MRI检测器官铁过载的结果做一综述。     

继发铁过载研究进展

继发铁过载多发生于输血依赖的患者,过量的铁沉积在重要器官,会对患者生存产生显著的影响.单纯依靠血清铁蛋白不能客观反映特定器官铁的沉积.评价体内铁过载的无创性方法主要有超导量子干涉仪和磁共振T2*.输血依赖的患者应定期监测体内铁过载的情况,并及时进行祛铁治疗.目前临床使用的祛铁剂主要有祛铁胺、祛铁酮和 Deferasimx.     

靶向肝星状细胞的基因治疗逆转肝纤维化的研究进展

<正>肝纤维化由肝脏受到慢性损伤后细胞外基质的过度沉积引起,激活的肝星状细胞(HSCs)是细胞外基质的主要来源。肝纤维化是许多慢性肝脏疾病的共同病理基础与特征,包括病毒性和自身免疫性肝炎,铁沉积,酒精性肝病和胆汁淤积等。目前认为肝脏细胞外基质的合成与降解失衡,导致其在肝内过度沉积是肝纤维化发展的主要机制。肝损伤导致HSCs活化     

Hepcidin在酒精性肝病发病中的作用研究进展

肝脏铁超负荷在酒精性肝病发病机制中起了重要的作用。铁调节蛋白(Hepcidin)是一种由肝脏分泌的小分子多肽,主要通过抑制肠道铁吸收和单核巨噬细胞系统铁释放来调控体内的铁稳态。近期研究发现,酒精可以影响铁调节蛋白在肝脏中的表达,导致肠道铁吸收及肝脏、单核巨噬细胞系统中铁利用再循环障碍,最终引起肝脏铁沉积。     

铁超负荷在大鼠酒精性肝病发病中的作用

目的探讨肝组织铁超负荷在酒精性肝病（ALD）发病中的作用。方法48只健康Wistar大鼠随机分为对照组（A组）和酒精灌胃组（B组）。A组和B组根据实验时间又分为5周和10周组（A5、A10、B5、B10）。分别测定各组大鼠血清ALT、AST,取肝组织行普鲁士兰染色观察铁颗粒沉积,并观察肝脏组织学改变。结果B5和B10组大鼠血清ALT和AST分别较A5和A10组升高,且B10组高于B5组;A组大鼠肝组织未见铁颗粒沉积,B组大鼠肝组织可见铁颗粒沉积,且B10组较B5组严重;B组大鼠肝组织可见脂肪变性和炎细胞浸润,且B10组更严重。结论铁超负荷在ALD的发病中起重要作用。     

去铁胺治疗骨髓增生异常综合征和原发性骨髓纤维化铁过载的临床研究

目的:探讨皮下注射去铁胺治疗输血依赖性铁过载血液病的疗效。方法:观察低危骨髓增生异常综合征和骨髓纤维化患者应用去铁胺治疗前后铁蛋白、肝脏、心脏等脏器功能改变和对去铁治疗的反应。结果:皮下注射去铁胺治疗输血依赖性铁过载的骨髓增生异常综合征和原发性骨髓纤维化1个月、4个月总反应率分别为33.3%,50.0%,不良反应少且可以耐受。结论:皮下注射去铁胺治疗输血依赖性铁过载的骨髓增生异常综合征和原发性骨髓纤维化疗效高、安全,有铁过载的患者应坚持用药。     

Interrelationships of alcohol and iron in liver disease with particular reference to the iron-binding proteins, ferritin and transferrin

It is known that the regular consumption of alcohol is responsible for the disruption of normal iron metabolism in humans, resulting in the excess deposition of iron in the liver in approximately one-third of alcoholic subjects. The mechanisms involved are largely unknown; however, it is likely that the two major proteins of iron metabolism, ferritin and transferrin are intimately involved in the process. Tissue damage in alcoholic liver disease and the inherited iron-overload disease, haemochromatosis, are caused by excess alcohol and iron, respectively. The mechanisms of this damage are believed to be similar in both disease conditions and involve free radical-mediated toxicity. A high proportion of haemochromatosis sufferers consume excessive amounts of alcohol and synergistic hepatotoxic events may occur leading to the earlier development of liver cirrhosis. This review describes briefly the role of ferritin and transferrin in normal iron metabolism and in iron overload disease and explores the possible involvement of these proteins in the pathophysiology of excess iron deposition in alcoholic subjects.     

铁超载在非酒精性脂肪性肝病中的作用

铁超载是非酒精性脂肪性肝病（NAFLD）的一个研究热点.从铁超载的评估方法、铁超载与血色病基因突变的关系、铁超载在NAFLD中的发生率及铁超载与NAFLD病情进展的关系等方面归纳了铁超载与NAFLD的相关性;从铁超载的原因、铁超载与脂质代谢的关系及铁沉积类型与肝损伤的关系评述了铁超载参与NAFLD进展的机制;从铁超载作为NAFLD危险分层的新标志物及可能的治疗靶点阐述了铁超载在NAFLD诊疗中的意义.目前认为不论铁超载是NAFLD进展的原因还是结果,一旦出现都将促进NAFLD进展;铁超载作为NAFLD危险分层的新标志物及治疗靶位值得进一步研究.     

Molecular pathogenesis and clinical conse-quences of iron overload in liver cirrhosis

BACKGROUND: The liver, as the main iron storage compart-ment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Exces-sive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases.
DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease pro-gression. We have also included literature on adjuvant thera-peutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis.
RESULTS: Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identiifcation of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause signiifcant improvement of liver functions in patients with iron overload. Phlebotomy can have beneifcial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology.
CONCLUSION: Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and avail-able data suggest that it can be considered as target for adju-vant therapy in this condition.     

Alcohol and iron: One glass of red or more?

The consumption of excessive amounts of alcohol affects human iron homeostasis and an association of iron overload and heavy alcohol consumption has been recognized for many years. Both major proteins of iron metabolism, ferritin and transferrin, are affected by alcohol. Increased hepatic iron levels are seen in a high proportion of alcoholic subjects, sometimes causing confusion in diagnosis between alcoholic liver disease and iron-overload disease. The pattern of deposition of this iron in alcoholics, however, differs from that seen in the iron-overload disease haemochromatosis. Excessive alcohol consumption causes transferrin to become carbohydrate deficient, which allows it to be used as an efficient biochemical marker of alcohol abuse. It is concluded that alcohol consumption in moderation is unlikely to have deleterious health consequences.     

Iron overload in Chinese patients with hemoglobin H disease

We examined the iron status of 23 adult patients with hemoglobin H (Hb H) disease. None of them had received multiple blood transfusions or prolonged iron therapy. Studies included serum iron and ferritin concentrations, transferrin saturation, a desferrioxamine test, computed tomography (CT) scan of the liver, and liver biopsy. Iron overload was found in 17 patients (73.9%), especially in males and in patients with splenomegaly (92.9% and 100%, respectively). Four patients with excessive alcohol consumption had clinical manifestations of severe iron overload. Idiopathic hemochromatosis associated HLA antigens, i.e., HLA-A3, -B7, or -B14, were not found in any of the 15 patients tested. These findings indicate that iron overload is common in adult patients with Hb H disease; such patients should abstain from alcohol and be considered for treatment with an iron chelating agent before irreversible organ damage occurs.     

Chelation therapy for iron overload

Iron overload is characterized by excessive iron deposition and consequent injury and dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Because physiologic mechanisms to excrete iron are very limited, patients with iron overload and its complications need safe, effective therapy that is compatible with their coexisting medical conditions. The availability of three licensed iron chelation drugs (one parenteral, two oral) and the development and clinical investigation of other oral chelators represent new opportunities to prevent or manage iron overload in patients with heritable types of severe anemia, such as β-thalassemia major and sickle cell disease, and for the formulation of alternatives to phlebotomy therapy for patients with iron overload associated with the HFE gene and other adult age-of-onset types of hemochromatosis, African iron overload, and African-American iron overload.     

Glucose abnormalities in non‐alcoholic fatty liver disease and chronic hepatitis C virus infection: the role of iron overload

Non‐alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection are major causes of liver disease frequently described in outpatient patients with glucose abnormalities. Hyperferritinemia, which suggests that iron overload plays a decisive role in the pathophysiology of insulin resistance and hyperglycemia, is a common finding in both disorders. However, the role of the hepatic iron deposition differs from one to the other. In NAFLD, a moderate liver iron accumulation has been observed and molecular mechanisms, including the downregulation of the liver iron exporter ferroportin‐1, have been described. Iron overload will enhance intrahepatic oxidative stress that promotes hepatic fibrosis, interfere with insulin signalling at various levels and may hamper hepatic insulin extraction. Therefore, liver fibrosis, hyperglycemia and hyperinsulinemia will lead to increased levels of insulin resistance and the development of glucose abnormalities. Furthermore, iron depletion by phlebotomy removes liver iron content and reduces serum glucose and insulin resistance in NAFLD patients. Therefore, it seems that iron overload participates in those glucose abnormalities associated with NAFLD. Concerning chronic HCV infection, it has been classically assumed that iron overload contributes to insulin resistance associated with virus infection. However, recent evidence argues against the presence of iron overload in these patients and points to inflammation associated with diabetes as the main contributor to the elevated ferritin levels. Therefore, glucose abnormalities, and specially type 2 diabetes, should be taken into account when evaluating serum ferritin levels in patients with HCV infection. Copyright © 2009 John Wiley & Sons, Ltd.     

Hepatic iron overload in alcoholic end-stage liver disease is associated with iron deposition in other organs in the absence of HFE-1 hemochromatosis.

BACKGROUND: End-stage cirrhosis in the absence of hereditary hemochromatosis (HHC) can be associated with moderate to marked hepatic iron overload, especially in liver disease as a result of alcohol and/or hepatitis C. However, no published studies have addressed extrahepatic iron deposition in this setting. METHOD: A retrospective case series from three autopsied patients who died from end-stage cirrhosis associated with significant hepatic iron overload. Histology of vital organs was performed to detect extrahepatic iron deposition. HFE genotyping for the C282Y and H63D mutations was determined from archival tissue. Hepatic iron index and hepatic iron concentration (HIC) were quantified from formalin-fixed, paraffin-embedded tissue. Medical records were reviewed for possible causes of iron overload. RESULTS: Two patients were H63D heterozygous (H63D +/-) and one was wild type (C282Y -/-, H63D -/-). Histology revealed evidence of stainable iron in the heart and pancreas of all three subjects. Additionally, stainable iron was seen in the stomach in one subject and in the thyroid, pituitary, choroid plexus and testes in another subject. HIC ranged from 4354 to 6834 microg/g dry weight and HII from 1.8 to 2.2 (micromol/g/years). CONCLUSION: Iron overload secondary to end-stage liver disease can be associated with iron deposition in other organs in the absence of HFE-1 HHC.     

Ineffective erythropoiesis and regulation of iron status in iron loading anaemias

The definition ‘iron loading anaemias’ encompasses a group of inherited and acquired anaemias characterized by ineffective erythropoiesis, low hepcidin levels, excessive iron absorption and secondary iron overload. Non‐transfusion‐dependent β‐thalassaemia is the paradigmatic example of these conditions that include dyserythropoietic and sideroblastic anaemias and some forms of myelodysplasia. Interrupting the vicious cycle between ineffective erythropoiesis and iron overload may be of therapeutic benefit in all these diseases. Induction of iron restriction by means of transferrin infusions, minihepcidins or manipulation of the hepcidin pathway prevents iron overload, redistributes iron from parenchymal cells to macrophage stores and partially controls anaemia in β‐thalassaemic mice. Inhibition of ineffective erythropoiesis by activin ligand traps improves anaemia and iron overload in the same models. Targeting iron loading or ineffective erythropoiesis shows promise in preclinical studies; activin ligand traps are in clinical trials with promising results and may be useful in patients with ineffective erythropoiesis.