Current status of novel antifibrotic therapies in patients with chronic liver disease.
Current status of novel antifibrotic therapies in patients with chronic liver disease.
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DOI：
10.1177/1756283x11413002
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发表时间：
2011-11-01
影响因子：
4.2
通讯作者：
Friedman, Scott L
中科院分区：
文献类型：
--
作者：
Cohen-Naftaly, Michal;Friedman, Scott L
肝纤维化堆积是由各种原因引起的急性或慢性肝损伤的伤口愈合反应所导致的动态过程。这一级联反应始于肝细胞的坏死和凋亡，它通过趋化因子和细胞因子激发炎症信号，重新聚集免疫细胞群，激活纤维化细胞，最终导致细胞外基质的沉积。这些关键要素，以及转录和表观遗传调节途径，代表了肥沃的治疗靶点。新的治疗方法包括专门设计的抗纤维化药物，以及已经有良好安全性的药物，其作用机制也可能是抗纤维化的。与此同时，非侵入性纤维化标志物和技术(如纤维扫描)的开发，以及结合血清和临床特征的综合评分系统的开发，将有助于改进对治疗反应的评估。总体而言，在阐明纤维化生物学方面的进展，结合改进的评估技术，将为抗纤维化药物的设计及其在精心设计的临床试验中的分析提供一个全面的框架。这些努力最终可能在阻止或逆转肝纤维化的进展方面取得成功。
Fibrosis accumulation is a dynamic process resulting from a wound-healing response to acute or chronic liver injury of all causes. The cascade starts with hepatocyte necrosis and apoptosis, which instigate inflammatory signaling by chemokines and cytokines, recruitment of immune cell populations, and activation of fibrogenic cells, culminating in the deposition of extracellular matrix. These key elements, along with pathways of transcriptional and epigenetic regulation, represent fertile therapeutic targets. New therapies include drugs specifically designed as antifibrotics, as well as drugs already available with well-established safety profiles, whose mechanism of action may also be antifibrotic. At the same time, the development of noninvasive fibrogenic markers, and techniques (e.g. fibroscan), as well as combined scoring systems incorporating serum and clinical features will allow improved assessment of therapy response. In aggregate, the advances in the elucidation of the biology of fibrosis, combined with improved technologies for assessment will provide a comprehensive framework for design of antifibrotics and their analysis in well-designed clinical trials. These efforts may ultimately yield success in halting the progression of, or reversing, liver fibrosis.