血吸虫病肝纤维化临床血清学诊断研究进展

血吸虫性肝纤维化是血吸虫病发展的最后阶段,可以导致门静脉高压、腹水和上消化道出血,甚至死亡。诊断方法包括影像学、病理学和血清学诊断3种。影像学诊断在肝纤维化晚期,才能出现异常图象;病理学诊断是金标准,但存在肝穿刺的盲目性、肝脏病变的不均一性而导致取样误差;血清学诊断是应用最广泛的诊断方法。     

肝纤维化的发病机制

1.肝纤维化的概念：1978年世界卫生组织专家组将纤维化定义为胶原的过度形成,因为当时认为胶原是纤维化肝脏最突出的结缔组织成分,经过20多年的研究,目前认为肝纤维化是指各种原因引起的动态创伤-愈合过程,在这个过程中,肝脏中的多种ECM成分含量不断增加。有研究表明,肝硬化时肝脏Ⅰ、Ⅲ、Ⅳ、Ⅴ、Ⅵ型胶原分别为正常肝脏的8、4、14、8和10倍,[第一段]     

肝纤维化血清学诊断研究进展

肝纤维化是各种慢性肝病进展至终末期肝病的必经阶段,在此阶段内对病情及时、准确地评估对疾病预后具有重要意义.近年来,肝纤维化的血清学诊断因其无创性和易重复性得到广泛重视,此文就其研究进展作一综述.     

肝纤维化血清学诊断研究进展

血清学诊断是研究最早、最广泛的肝纤维化诊断方法,其取材方便,价格低廉,因而较为实用。　　胶原蛋白对肝纤维化的诊断价值胶原蛋白在正常肝脏内约占蛋白总量的5%～10%,肝硬变时,胶原蛋白可增加到50%左右,目前发现肝内有5种主要胶原蛋白,分别是、、、、型胶原蛋白,其中又以、型为主。一、型胶原(C):目前报道测定C应用最广泛的是检测型前胶原氨基端肽(PP)和型前胶原(PC)。大多数学者认为PP与肝纤维化的活动度有密切关系,血清PP水平随肝纤维化程度的增加而升高,可作为反映肝纤维化活动度和程度的一项指标,同时与肝脏炎症、坏死也有关。Gu…     

活性氧簇与肝纤维化发病的研究进展

肝星状细胞(HSC)的激活是肝纤维化发病的中心事件,而活性氧簇(ROS)是肝纤维化发病的重要介质.不同来源的ROS在HSC激活的各个阶段所起的作用不同,它参与了肝纤维化发病的全过程.     

肝纤维化临床诊断与治疗研究进展

<正>1 肝纤维化的定义、流行病学和发生机制1.1 定义器官硬化和纤维化不仅是疾病长期进展的结果,也是机体发生衰老的过程,诸如肝、胰腺、肠、肺、肾、心、脑、血管、皮肤和关节等几乎所有器官均可发生纤维化和硬化。纤维化对机体的影响是一把“双刃剑”,其虽可以促进组织损伤的修复,但过度的纤维沉积会破坏组织结构并导致血运障碍。在各种因素的作用下,肝内胶原、糖蛋白和蛋白多糖等细胞外基质成分的过度沉积称为肝纤维化。肝纤维化是可逆的过程,     

肝纤维化形成机制研究进展

肝纤维化是继发于肝脏炎症或损伤后组织修复过程中的代偿性反应 ,以细胞外基质 (ＥＣＭ )在肝内过量沉积为病理特征。肝纤维化已成为世界范围内的一个主要健康问题。现已证实肝纤维化发生的中心事件是 :由损伤所引起的肝星状细胞(ＨＳＣ)的激活及其转化为肌成纤维细胞 ,从而大量合成各种细胞外基质蛋白 ,沉积于肝脏最终导致肝纤维化。本文就肝星状细胞的激活及调控对近年来肝纤维化形成机制的有关进展作一简介。一、肝星状细胞的活化与ＥＣＭ的产生ＨＳＣ是肝脏间质细胞之一 ,位于肝细胞与窦内皮细胞间的Ｄｉｓｓｅ腔内。正常时呈静止状态 ,…     

肝纤维化无创性诊断的研究进展

肝纤维化是各种慢性肝病损伤修复过程的共同后果,作为损伤的标记物之一,其在肝细胞性功能障碍和门静脉性高压的发病机制中起直接作用。同时,肝纤维化、甚至早期肝硬化具有可逆性已成为共识。因此从临床治疗角度而言,正确评估肝纤维化的程度和进展显得十分重要。本文就以肝纤维化的诊断,特别是无创性诊断的研究进展作一综述。     

HSC凋亡与肝纤维化逆转的研究进展

肝星状细胞(HSC)在肝纤维化形成中起核心作用,其凋亡是肝纤维化逆转的主要机制之一.深入研究HSC凋亡的调控机理及HSC凋亡在肝纤维化逆转中的作用,对肝纤维化的防治具有重要意义.     

肝纤维化发生机制的研究进展

近年来对肝炎后肝硬化发病机制的研究有了长足进展,尤其在对肝细胞外基质的研究方面,胶原纤维合成（ｆｉｂｒｏｇｅｎｅｓｉｓ）和纤维溶解（ｆｉｂｒｏｇｅｎｏｌｙｓｉｓ）维持动态平衡,例如对与胶原合成酶相对抗的多种基质金属蛋白酶（ｍａｔｒｉｘｍｅｔａｌｏｐｒ...     

Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: An update

There have been considerable recent advances towards a better understanding of the complex cellular and molecular network underlying liver fibrogenesis. Recent data indicate that the termination of fibrogenic processes and the restoration of deficient fibrolytic pathways may allow the reversal of advanced fibrosis and even cirrhosis. Therefore, efforts have been made to better clarify the cellular and molecular mechanisms that are involved in liver fibrosis. Activation of hepatic stellate cells (HSCs) remains a central event in fibrosis, complemented by other sources of matrix-producing cells, including portal fibroblasts, fibrocytes and bone marrow-derived myofibroblasts. These cells converge in a complex interaction with neighboring cells to provoke scarring in response to persistent injury. Defining the interaction of different cell types, revealing the effects of cytokines on these cells and characterizing the regulatory mechanisms that control gene expression in activated HSCs will enable the discovery of new therapeutic targets. Moreover, the characterization of different pathways associated with different etiologies aid in the development of disease-specific therapies. This article outlines recent advances regarding the cellular and molecular mechanisms involved in liver fibrosis that may be translated into future therapies. The pathogenesis of liver fibrosis associated with alcoholic liver disease, non-alcoholic fatty liver disease and viral hepatitis are also discussed to emphasize the various mechanisms involved in liver fibrosis.     

Iron and liver fibrosis: Mechanistic and clinical aspects

Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality. It is a pathological stage in several untreated chronic liver diseases such as the iron overload syndrome hereditary haemochromatosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and diabetes. Interestingly, regardless of the aetiology, iron-loading is frequently observed in chronic liver diseases. Excess iron can feed the Fenton reaction to generate unquenchable amounts of free radicals that cause grave cellular and tissue damage and thereby contribute to fibrosis. Moreover, excess iron can induce fibrosis-promoting signals in the parenchymal and non-parenchymal cells, which accelerate disease progression and exacerbate liver pathology. Fibrosis regression is achievable following treatment, but if untreated or unsuccessful, it can progress to the irreversible cirrhotic stage leading to organ failure and hepatocellular carcinoma, where resection or transplantation remain the only curative options. Therefore,understanding the role of iron in liver fibrosis is extremely essential as it can help in formulating iron-related diagnostic, prognostic and treatment strategies. These can be implemented in isolation or in combination with the current approaches to prepone detection, and halt or decelerate fibrosis progression before it reaches the irreparable stage. Thus, this review narrates the role of iron in liver fibrosis. It examines the underlying mechanisms by which excess iron can facilitate fibrotic responses. It describes the role of iron in various clinical pathologies and lastly,highlights the significance and potential of iron-related proteins in the diagnosis and therapeutics of liver fibrosis.     

肝纤维化的靶向治疗

肝纤维化是各种致病因子造成肝细胞损伤,激活库普弗细胞并使之分泌多种细胞因子,随同血小板、炎性细胞等分泌的多种细胞因子共同作用于HSC,使之转化为肌成纤维细胞；细胞因子同时激活纤维母细胞,合成并分泌大量的ECM沉积在肝Disse间隙内,抑制肝细胞生长因子及胶原酶的合成和分泌,导致肝纤维化形成,Ⅰ、Ⅲ型胶原是ECM的主要成分。[第一段]     

肝纤维化发生相关信号传导通路研究进展

肝纤维化(Hepatic fibrosis,HF)是肝脏对于各种慢性刺激损伤进行自我修复的一种病理过程,具有修复和损伤双重性并最终可能发展为肝硬化、肝功能衰竭,甚至肝癌。如何延缓、停止、逆转肝纤维化的发展显得尤为重要。肝纤维化是一个复杂的病变过程,由多种细胞因子及多条细胞信号传导通路共同控制。深入研究各信号通路的发生机制,可望寻找到有效的干预途径,以达到防治肝纤维化的目的。     

Angiogenesis and liver fibrosis

Recent data indicate that hepatic angiogenesis, regardless of the etiology, takes place in chronic liver diseases (CLDs) that are characterized by inflammation and progressive fibrosis. Because anti-angiogenic therapy has been found to be efficient in the prevention of fibrosis in experimental models of CLDs, it is suggested that blocking angiogenesis could be a promising therapeutic option in patients with advanced fibrosis. Consequently, efforts are being directed to revealing the mechanisms involved in angiogenesis during the progression of liver fibrosis. Literature evidences indicate that hepatic angiogenesis and fibrosis are closely related in both clinical and experimental conditions. Hypoxia is a major inducer of angiogenesis together with inflammation and hepatic stellate cells. These profibrogenic cells stand at the intersection between inflammation, angiogenesis and fibrosis and play also a pivotal role in angiogenesis. This review mainly focuses to give a clear view on the relevant features that communicate angiogenesis with progression of fibrosis in CLDs towards the-end point of cirrhosis that may be translated into future therapies. The pathogenesis of hepatic angiogenesis associated with portal hypertension, viral hepatitis, non-alcoholic fatty liver disease and alcoholic liver disease are also discussed to emphasize the various mechanisms involved in angiogenesis during liver fibrogenesis.     

Investigation of liver fibrosis in clinical practice.

The liver is composed of different hepatic fibrogenic cells: hepatic stellate cells, portal fibroblasts, fibroblasts of the Glisson capsule surrounding the liver and vascular smooth muscle cells and the second layer cells present around centrolobular veins. During liver disease, one or several populations of these cells are activated, transformed into myofibroblasts and secrete the extra-cellular matrix. There are markers to identify hepatic stellate cells either quiescent (CRBP-1) or activated (alpha-smooth muscle actin). Liver biopsy, the current "gold-standard" to estimate liver fibrosis cannot be used anymore as a "gold standard". Furthermore, it is a costly procedure with adverse effects feared by patients and clinicians. Alternative to liver biopsy using non-invasive-tests or technics include FibroTest-ActiTest, transient-elastography, hepatic vein transit time using contrast ultrasonography, magnetic resonance imaging. As a routine test, the FibroTest-ActiTest is a validated one for patients with chronic hepatitis C. The advantage of the non-invasive tests or technics is that they provide a rapid and quantitative estimation of fibrosis. With these new methods, it is possible to follow the progression of the disease and its regression either spontaneously or under treatment. In conclusion, clinicians have in their hands several painless tools to explore liver fibrosis that can be easily repeated.     

Autophagy: A new therapeutic target for liver fibrosis

Hepatic fibrosis is a wound-healing response to liver injury and the result of imbalance of extracellular matrix (ECM) accumulation and degradation. The relentless production and progressive accumulation of ECM can lead to end-stage liver disease. Although significant progress has been achieved in elucidating the mechanisms of fibrogenesis, effective anti-fibrotic strategies are still lacking. Autophagy is an intracellular process of self-digestion of defective organelles to provide material recycling or energy for cell survival. Autophagy has been implicated in the pathophysiology of many human disorders including hepatic fibrosis. However, the exact relationships between autophagy and hepatic fibrosis are not totally clear and need further investigations. A new therapeutic target for liver fibrosis could be developed with a better understanding of autophagy.     

促纤维化因子在肝纤维化发生中的作用研究进展

肝纤维化是多种病因所致的慢性肝损伤的一种创伤愈合反应,持续的炎症与纤维形成最终导致肝硬化。肝星状细胞（HSC）是肝纤维化的主要生成细胞,肝脏内细胞外基质（ECM）的过度沉积是其主要功能。各种促纤维化因子如血管紧张素-II（AngII）、血小板衍生生长因子（PDGF）、血管内皮生长因子（VEGF）、转化生长因子-β（TGF-β）、瘦素、结缔组织因子等可与HSC表面上相应的受体结合,并激活相应的信号通路,进而导致HSC的激活、增殖,ECM过度沉积,引起肝纤维化形成。因此,了解各种促纤维化因子与肝纤维化的关系,可为抗纤维化的科学研究及临床治疗提供理论依据。     

肝星状细胞活化相关信号通路在肝纤维化中的研究进展

肝纤维化是多种慢性肝损伤造成的细胞外基质(extracellular matrix, ECM)过度累积及降解不足的病理结果,如不加以干预会逐渐进展为肝硬化,甚至肝细胞癌。肝星状细胞(hepatic stellate cell, HSC)是ECM的主要来源,并且HSC在肝纤维化的起始、发展和消退过程中发挥关键作用。近年来,HSC活化涉及的信号传导通路成为研究热点,本文总结了HSC活化过程中的重要信号通路。     

肝星状细胞凋亡调控因素的研究进展

诱导HSC凋亡成为阻止肝纤维化进程的途径之一.生长因子、死亡受体配体(TRAIL、FAS)、细胞外基质(胶原、整合素)、信号转导蛋白和转录因子(NF-κB、IKKJNK)等多种因素参与调控HSC凋亡.