Bataller R, Brenner D A
University of North Carolina at Chapel Hill, School of Medicine, C.B. 7038, Chapel Hill, NC 27599, USA.
Semin Liver Dis. 2001 Aug;21(3):437-51. doi: 10.1055/s-2001-17558.
Following chronic liver injury of any etiology, there is progressive fibrosis. To date, removing the causative agent is the only effective therapy to stop or even reverse liver fibrosis. Therefore, the development of effective antifibrotic therapies represents a challenge for modern hepatology. In the past decade, dramatic advances have been made in the understanding of the cellular and molecular mechanisms underlying liver fibrogenesis. The identification of activated hepatic stellate cells (HSCs) as the major fibrogenic cell type in the injured liver, as well as the recognition of key cytokines involved in this process, have facilitated the design of promising new antifibrotic therapies. These therapies are aimed at inhibiting the accumulation of activated HSCs at the sites of liver injury and preventing the deposition of extracellular matrix. Although many of these approaches are effective in experimental models of liver fibrosis, their efficacy and safety in humans are still unknown. This review describes the current therapeutic approaches for liver fibrosis and discusses different features of activated HSCs as a target to design new treatments to inhibit scar formation in chronic liver diseases.
在任何病因导致的慢性肝损伤之后，都会出现进行性纤维化。迄今为止，去除致病因素是阻止甚至逆转肝纤维化的唯一有效疗法。因此，开发有效的抗纤维化疗法是现代肝病学面临的一项挑战。在过去十年中，我们对肝纤维化发生的细胞和分子机制的理解取得了巨大进展。已确定活化的肝星状细胞（HSC）是受损肝脏中主要的纤维化细胞类型，并且认识到参与这一过程的关键细胞因子，这有助于设计有前景的新型抗纤维化疗法。这些疗法旨在抑制活化的HSC在肝损伤部位的积聚，并防止细胞外基质的沉积。尽管这些方法中的许多在肝纤维化实验模型中有效，但其在人体中的疗效和安全性仍然未知。本综述描述了目前治疗肝纤维化的方法，并讨论了活化HSC作为设计新疗法以抑制慢性肝病瘢痕形成靶点的不同特征。
