血清肝纤维化标志物研究进展

肝纤维化持续发展可演变为不可逆的肝硬化。然而,肝纤维化是可以通过药物、基因等干预措施而逆转的,因此早期准确诊断肝纤维化对于临床判断疾病预后和确定治疗策略具有重要的价值。本文重点介绍了各种直接和间接生物标记的血清学指标在肝纤维化诊断方面的应用和进展情况。探讨各种血清学指标的诊断价值,以期获得诊断早期肝纤维化的最佳指标,为制定治疗方案和判断疗效提供参考。     

重视肝纤维化的诊治

肝纤维化是各种病因引起慢性反复肝损伤后的疤痕修复反应,是肝硬化发生的早期、可逆阶段。概述了肝纤维化与肝硬化的区别和慢性肝病的分期方法,重点论述了肝纤维化早期诊治的重要性,介绍了目前早期诊断评估方法以及肝纤维化的药物开发与治疗进展。强调肝纤维化患者的诊断及治疗对防止肝病进展为失代偿期肝硬化具有重要意义。     

肝纤维化非创伤性诊断评估及其临床应用

肝纤维化是一种代偿修复反应,呈慢性、渐进性过程。各种病因引起的慢性肝脏疾病都存在有肝纤维化,其中25%~40%最终进展为肝硬化甚至肝癌。判断肝纤维化的程度对于预后评估、选择抗纤维化治疗药物及其疗效考核具有重要的临床意义。经皮肝穿刺活检仍然是诊断肝纤维化的"金标准",但因其存在有创性、取样误差及不同观察者间     

以肝星状细胞为靶向的药物载体系统

肝星状细胞是抗肝纤维化治疗的重要靶点,如何安全有效地将治疗药物靶向递送至肝星状细胞,提高药物疗效,减小药物脱靶的毒副作用,是目前抗肝纤维化药物开发的重要策略。许多蛋白标志物在活化的肝星状细胞中表达升高,因此它们的配体被用来特异性地传递各种抗纤维化药物。从受体靶向及药物载体的种类方面总结了目前靶向肝星状细胞治疗肝纤维化的研究进展。     

抗肝纤维化的治疗策略

肝纤维化是指肝脏弥漫性纤维结缔组织沉积,有效干预可显著改善患者预后。病因治疗是肝纤维化最首要和最有效的治疗措施,针对肝纤维化发病机制的不同环节,近年来研发了不少抗肝纤维化的治疗药物．主要通过抗炎抗氧化、针对特异性细胞因子及细胞内信号转导、抑制纤维化形成、促进纤维降解等发挥作用。靶向治疗和干细胞治疗也在日臻进步。近年来关于肝纤维的临床注册研究越来越多,我们也从中得到了关于抗肝纤维化临床研究设计的有益经验。随着对肝纤维化发病机制研究的不断深入、无创肝纤维化诊断方法的不断探索和大量抗纤维化药物的临床前及临床试验的不断开展,必然使肝纤维化患者在不久的将来有望得到有效抗肝纤维化治疗。     

肝纤维化的治疗策略及药物治疗进展

肝纤维化是各种不同致病因子引起慢性肝病进而发展为肝硬化的共有病理改变及必经途径,其防治是当今肝病治疗的难点之一。本文就肝纤维化的发病机制、肝纤维化的治疗策略及抗肝纤维化的药物研究进展等方面作一综述。     

肝纤维化诊断措施的评价

肝纤维化是一种代偿修复反应,呈慢性的渐进性过程.各种病因引起的慢性肝病都存在肝纤维化,其中25%～40%最终发展为肝硬化,甚至肝癌.判断肝纤维化程度非常重要,对预后评估、选择抗纤维化治疗药物及其疗效评价具有重要临床意义.目前仍未建立准确性高的非创伤性诊断方法,肝纤维化的诊断尚离不开肝穿刺活组织检查.     

肝纤维化的治疗策略及药物治疗进展

肝纤维化是各种不同致病因子引起慢性肝病进而发展为肝硬化的共有病理改变及必经途径，其防治是当今肝病治疗的难点之一。本就肝纤维化的发病机制、肝纤维化的治疗策略及抗肝纤维化的药物研究进展等方面作一综述。     

CT、磁共振定量诊断肝纤维化的研究进展

肝纤维化是肝脏对各种病因所致的肝损伤的修复愈合反应,也是各种慢性肝病向肝硬化发展的中间阶段。肝纤维化发展过程是潜隐渐进而可逆的。肝纤维化能否得到及时和正确的诊断,对临床治疗效果及患者预后有着重要的意义。随着影像技术的发展完善,肝纤维化的无创性影像定量诊断备受临床关注。总结了目前用于肝纤维化诊断的各种CT、磁共振（MR）扫描技术,就各种技术的优缺点进行了比较。结果表明CT、MR可对肝纤维化进行定量评估,尤其MR无辐射、高分辨率、可重复性好在将来完全有可能取代有创的病理检查。     

肝纤维化非创伤性诊断

肝纤维化是各种慢性肝损伤发展为肝硬化的共同病理过程，对其早期诊断可为药物治疗、预防和预后判断等提供重要的参考。长期以来，肝纤维化的确诊离不开肝活组织检查，这种损伤性检查具有明显不足。因此临床上迫切需要寻找简单且易推广的非创伤性诊断指标诊断肝纤维化。目前仅依靠某种或某几类指标诊断肝纤维化显然是不够全面的，而且这些诊断指标必需经过系列的大样本进行验证以便进一步证实其诊断肝纤维化的准确性。近来在肝纤维化非创伤性诊断方面有不少有价值的临床研究，这些结果对临床医生有很重要的参考价值。     

Consensus on the diagnosis and treatment of hepatic fibrosis (2019)

Hepatic fibrosis is a reparative response of diffuse over‐deposition and abnormal distribution of extracellular matrix (collagen, glycoprotein and proteoglycans) after exposure to various kinds of liver injuries, and is a key step in the developmental process of various chronic liver diseases leading to cirrhosis. Recently, many advances in our understanding of hepatic fibrosis have been obtained through basic and clinical research. Therefore, this consensus summarizes and offers 15 evidence‐based recommendations on the diagnosis and evaluation of hepatic fibrosis, its treatment, drug development and applications.     

肝纤维化血清学诊断研究进展

肝纤维化是由各种慢性肝病引起细胞外基质在肝脏过度沉积所致,可进展为肝硬化并导致肝功能衰竭和门静脉高压等。肝纤维化具有可逆性已成为共识。因此,准确诊断和评估肝纤维化程度对肝纤维化的防治及其预后评估具有非常重要的意义。肝纤维化诊断的金标准是肝脏活检,但由于其具有创伤性、费用昂贵而难以被患者接受。血清学检查是诊断肝纤维化较为理想的检测方法,可对肝纤维化进行早期诊断,并可进行动态观察。由多个血清学指标组成的非创伤性诊断模型,提高了肝纤维化的诊断准确性。本文就肝纤维化的血清学诊断研究进展进行综述。     

Clinical Application of Transient Elastography in the Diagnosis of Liver Fibrosis: an Expert Panel Review and Opinion

Liver fibrosis evaluation is pivotal for treatment decisions and prognosis assessment in patients with chronic liver disease. Liver transient elastography (TE) is a newly developed non-invasive technique for diagnosis of liver fibrosis. It can assess the state of liver fibrosis by liver stiffness measurements, and offers better performance for the diagnosis of liver cirrhosis than serum biological markers. It has now been approved for clinical use in China. The aim of this review is to provide a guide for clinicians to apply this technique appropriately. The recommendations are made under the auspices of China Foundation for Hepatitis Prevention and Control, and have been prepared by a panel experts, who have reviewed and summarized the clinical studies on TE in order to develop these recommendations.     

Non-invasive diagnosis of liver fibrosis: A review of current imaging modalities

Hundreds of millions of patients are suffering from cirrhosis and other chronic liver diseases worldwide, and this public health problem continues to grow. It has been proven that liver fibrosis is reversible after the elimination of the etiology, especially in the early stage. Thus, early diagnosis of liver fibrosis is of vital importance for clinical treatment. Liver biopsy remains the gold standard for both diagnosis and staging of fibrosis, but is suboptimal, due in large parts to its invasive nature and sundry associated complications. To overcome this, a number of non-invasive diagnosis based on serum biomarkers or imaging modalities have been developed. While diagnosis based on serum biomarkers is cheaper and more acceptable to patients, almost none developed to date are liver-specific, and may engender a false positive error. The imaging modalities have evolved rapidly and are taking on more and more important roles in the diagnosis of liver fibrosis.     

肝纤维化血清学无创检测研究进展

肝纤维化指肝脏细胞外基质弥漫性的过度沉积,是机体对于肝实质损伤的一种修复反应及许多慢性肝病共同的病理过程,也是各种慢性肝病向肝硬化发展的重要步骤.迄今为止,临床尚缺乏特异性有效逆转或阻止肝纤维化进展的药物,尽早对肝纤维化进行诊断具有重要意义.目前肝纤维化的诊断主要靠组织病理学、血清学标志物及影像学手段.肝活检被认为是肝...     

Role of noncoding RNAs in liver fibrosis

Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection, obesity, or excessive alcohol. It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix. Advanced fibrosis could lead to cirrhosis and even liver cancer, which has become a significant health burden worldwide. Many studies have revealed that noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs and circular RNAs, are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-β pathway, phosphatidylinositol 3-kinase/protein kinase B pathway, and Wnt/β-catenin pathway. NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis. NcRNAs mimics, ncRNAs in mesenchymal stem cell-derived exosomes, and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis. In this review, we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis, and discuss the potentials and challenges to use these ncRNAs for diagnosis, staging and treatment of liver fibrosis. All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.     

超声技术无创评估肝纤维化的临床应用进展

肝纤维化可发展为肝硬化,其中部分可进展为肝癌、肝衰竭。因此肝纤维化程度的评估对临床治疗、预后评价非常重要,而超声弹性成像是一种新的无创性评估肝纤维化程度的方法,为肝纤维化的早期诊断提供了新思路。本文就其在肝纤维化诊断中的应用进行综述。     

不同亚型Numb蛋白对肝纤维化相关信号通路的影响

肝纤维化是各种慢性肝病发展为肝硬化的必经之路,是一个可逆的病理状态。但如何阻抑或逆转肝纤维化的发生与发展,仍是临床需要解决的重要科学问题。Numb,一个重要的细胞命运决定子,已被发现与多种疾病的发生密切相关。在肝纤维化环境中,由于Numb基因的选择性剪切作用,翻译出不同亚型的Numb蛋白,其对不同信号通路的活化以及肝干细胞的分化具有不同的调节作用。目前关于Numb蛋白不同亚型在肝纤维化中的作用报道较少。综述了不同亚型Numb蛋白对Notch、Hedgehog、P53信号通路以及对肝干细胞的调控作用,阐释其在肝纤维化治疗中的潜在应用前景。     

Fibrosis assessment: impact on current management of chronic liver disease and application of quantitative invasive tools

Fibrosis, a common pathogenic pathway of chronic liver disease (CLD), has long been indicated to be significantly and most importantly associated with severe prognosis. Nowadays, with remarkable advances in understanding and/or treatment of major CLDs such as hepatitis C, B, and nonalcoholic fatty liver disease, there is an unprecedented requirement for the diagnosis and assessment of liver fibrosis or cirrhosis in various clinical settings. Among the available approaches, liver biopsy remains the one which possibly provides the most direct and reliable information regarding fibrosis patterns and changes in the parenchyma at different clinical stages and with different etiologies. Thus, many endeavors have been undertaken for developing methodologies based on the strategy of quantitation for the invasive assessment. Here, we analyze the impact of fibrosis assessment on the CLD patient care based on the data of recent clinical studies. We discuss and update the current invasive tools regarding their technological features and potentials for the particular clinical applications. Furthermore, we propose the potential resolutions with application of quantitative invasive tools for some major issues in fibrosis assessment, which appear to be obstacles against the nowadays rapid progress in CLD medicine.