Centre for Inflammation Research to MRC, University of Edinburgh Centre for Inflammation Research, Edinburgh, United Kingdom.
Ann Hepatol. 2009 Oct-Dec;8(4):283-91.
Liver cirrhosis is a major cause of morbidity and mortality worldwide and has very limited therapeutic options. Regardless of the aetiology, hepatic fibrosis is a characteristic feature of chronic liver disease. Our knowledge regarding the pathogenesis of this scarring has grown exponentially in the past 25 years. It has now clear that this is a highly dynamic process and the long-held dogma that it is irreversible and relentlessly progressive is now being challenged. In this review, we will summarise the key pathogenic mechanisms at play and will focus on the evidence demonstrating that liver fibrosis is reversible in humans and animal models. In particular, we will examine the role of hepatic stellate cells, MMPs, TIMPs and macrophages in this process. Finally, we will discuss some of the studies aimed to therapeutically target the resolution of fibrosis and their potential for translation into a badly-needed treatment modality in the clinical setting.
肝硬化是全球范围内发病率和死亡率的主要原因,且其治疗选择非常有限。无论病因如何,肝纤维化都是慢性肝病的一个特征。在过去的 25 年中,我们对这种瘢痕形成的发病机制的了解呈指数级增长。现在很明显,这是一个高度动态的过程,长期以来认为它是不可逆转的、无情进展的观点现在正受到挑战。在这篇综述中,我们将总结发挥作用的关键发病机制,并重点介绍证明肝纤维化在人类和动物模型中是可逆的证据。特别是,我们将研究肝星状细胞、基质金属蛋白酶、基质金属蛋白酶抑制剂和巨噬细胞在这一过程中的作用。最后,我们将讨论一些旨在治疗纤维化消退的研究及其在临床环境中转化为急需的治疗方式的潜力。