NF-κB in the liver—linking injury, fibrosis and hepatocellular carcinoma

By Tom Luedde, Robert F. Schwabe. Nature Reviews Gastroenterology &Hepatology, 2011

1,228 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Epidemiology, Hepatology

View Paper: https://www.semanticscholar.org/paper/1958096baf988a432d28bd2b26ba2f72803aea66

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Robert F. Schwabe
2. R. Sartor

In Epidemiology

1. Robert F. Schwabe
2. Natascha Roehlen
3. E. Crouchet
4. T. Baumert
5. R. Sartor

In Hepatology

1. Natascha Roehlen
2. E. Crouchet
3. T. Baumert
4. Robert F. Schwabe

Citations in the corpus

• Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4 (2012, background): “Notably, 80% of HCCs develop in fibrotic or cirrhotic livers as a consequence of chronic liver injury (Fattovich et al., 2004; Luedde and Schwabe, 2011) with HCC being the leading cause of death in patients with compensated liver cirrhosis (Fattovich et al., 2004).”
• Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives (2020, background): “NF-κB has a key role in the regulation of cell death, inflammation, and wound healing and is therefore an important modulator of liver fibrosis progression [156].”