Clin Mol Hepatol.  2021 Jul;27(3):413-424. 10.3350/cmh.2020.0187.

Anti-fibrotic treatments for chronic liver diseases: The present and the future

• Odagiri N
• Matsubara T
• Sato-Matsubara M
• Fujii H
• Enomoto M
• Kawada N

• KMID: 2517624
• DOI: http://doi.org/10.3350/cmh.2020.0187

Abstract

Liver fibrosis reflects tissue scarring in the liver due to the accumulation of excessive extracellular matrix in response to chronically persistent liver injury. Hepatocyte cell death can trigger capillarization of liver sinusoidal endothelial cells, stimulation of immune cells including macrophages and Kupffer cells, and activation of hepatic stellate cells (HSCs), resulting in progression of liver fibrosis. Liver cirrhosis is the terminal state of liver fibrosis and is associated with severe complications, such as liver failure, portal hypertension, and liver cancer. Nevertheless, effective therapy for cirrhosis has not yet been established, and liver transplantation is the only radical treatment for severe cases. Studies investigating HSC activation and regulation of collagen production in the liver have made breakthroughs in recent decades that have advanced the knowledge regarding liver fibrosis pathophysiology. In this review, we summarize molecular mechanisms of liver fibrosis and discuss the development of novel anti-fibrotic therapies.

Keyword

Fibrosis; Hepatic stellate cells; Myofibroblasts; Extracellular matrix; Drug therapy