Department of Internal Medicine III, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Pauwelsstraße 30, Aachen, Germany.
Nat Rev Gastroenterol Hepatol. 2011 Feb;8(2):108-18. doi: 10.1038/nrgastro.2010.213.
Hepatic cirrhosis and hepatocellular carcinoma (HCC) are the most common causes of death in patients with chronic liver disease. Chronic liver injury of virtually any etiology triggers inflammatory and wound-healing responses that in the long run promote the development of hepatic fibrosis and HCC. Here, we review the role of the transcription factor nuclear factor-κB (NF-κB), a master regulator of inflammation and cell death, in the development of hepatocellular injury, liver fibrosis and HCC, with a particular focus on the role of NF-κB in different cellular compartments of the liver. We propose that NF-κB acts as a central link between hepatic injury, fibrosis and HCC, and that it may represent a target for the prevention or treatment of liver fibrosis and HCC. However, NF-κB acts as a two-edged sword and inhibition of NF-κB may not only exert beneficial effects but also negatively impact hepatocyte viability, especially when NF-κB inhibition is pronounced. Finding appropriate targets or identifying drugs that either exert only a moderate effect on NF-κB activity or that can be specifically delivered to nonparenchymal cells will be essential to avoid the increase in liver injury associated with complete NF-κB blockade in hepatocytes.
肝硬化和肝细胞癌（HCC）是慢性肝病患者死亡的最常见原因。几乎任何病因的慢性肝损伤都会引发炎症和伤口愈合反应，这些反应从长远来看会促进肝纤维化和 HCC 的发展。在这里，我们回顾了转录因子核因子-κB（NF-κB）在肝细胞损伤、肝纤维化和 HCC 发展中的作用，特别关注 NF-κB 在肝脏不同细胞区室中的作用。我们提出 NF-κB 是肝损伤、纤维化和 HCC 之间的中心联系，它可能是预防或治疗肝纤维化和 HCC 的靶点。然而，NF-κB 是一把双刃剑，抑制 NF-κB 不仅可能产生有益的效果，还可能对肝细胞的存活产生负面影响，尤其是当 NF-κB 抑制作用明显时。找到合适的靶点或确定仅对 NF-κB 活性产生适度影响的药物，或者可以将其专门递送到非实质细胞，对于避免与完全阻断肝细胞中 NF-κB 相关的肝损伤增加至关重要。
