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肝纤维化的新兴疗法。

Emerging therapies for liver fibrosis.

作者信息

Fowell Andrew J, Iredale John P

机构信息

Liver Research Group, Division of Infection, Inflammation and Repair, University of Southampton, Southampton General Hospital, Southampton, UK.

出版信息

Dig Dis. 2006;24(1-2):174-83. doi: 10.1159/000090320.

Abstract

Liver fibrosis occurs as a result of a wide range of injurious processes and in its end-stage results in cirrhosis. This gross disruption of liver architecture is associated with impaired hepatic function, portal hypertension and significant resultant morbidity and mortality. Indeed, liver fibrosis and cirrhosis represent a major worldwide healthcare burden. Recent progress in liver transplantation, the management of portal hypertension and the treatment of chronic viral hepatitis have had an important impact. However, these approaches are not without their limitations - in particular, issues regarding organ availability for transplantation - and serve to highlight the urgent requirement to influence pharmacologically the underlying fibrotic process in many patients. Liver fibrosis has been shown to be a bidirectional process and increasing data from laboratory and clinical studies reveal that even advanced fibrosis and cirrhosis are potentially reversible. Exploration of the molecular mechanisms underlying this bi-directionality will lead to char acterisation of the essential attributes of an antifibrotic therapy. In this review, these mechanisms are highlighted and the growing number of emerging antifibrotic agents discussed.

摘要

肝纤维化是由多种损伤过程引起的,在其终末期会导致肝硬化。肝脏结构的这种严重破坏与肝功能受损、门静脉高压以及由此导致的显著发病率和死亡率相关。事实上,肝纤维化和肝硬化是全球主要的医疗负担。肝移植、门静脉高压管理和慢性病毒性肝炎治疗方面的最新进展产生了重要影响。然而,这些方法并非没有局限性——特别是关于移植器官可用性的问题——这凸显了在许多患者中通过药物影响潜在纤维化过程的迫切需求。肝纤维化已被证明是一个双向过程,来自实验室和临床研究的越来越多的数据表明,即使是晚期纤维化和肝硬化也可能是可逆的。探索这种双向性背后的分子机制将有助于确定抗纤维化治疗的基本特性。在这篇综述中,将重点介绍这些机制,并讨论越来越多新出现的抗纤维化药物。

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