title: NF-κB in the liver--linking injury, fibrosis and hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Internal Medicine III, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Pauwelsstraße 30, Aachen, Germany. tluedde@ukaachen.de
authors.forename: Tom
authors.initials: T
authors.lastname: Luedde
authors.forename: Robert F
authors.initials: RF
authors.lastname: Schwabe
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D002470:Cell Survival / Q000502:physiology; D005355:Fibrosis; D022781:Hepatocytes / Q000473:pathology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000503:physiopathology; D008113:Liver Neoplasms / Q000503:physiopathology*; D016328:NF-kappa B / Q000502:physiology*
chemical_list: D016328:NF-kappa B