Inhibition of Hepatic Fibrogenesis: A Review of Pharmacologic Candidates

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Abstract
Hepatic fibrosis is a dynamic process from chronic liver damage to cirrhosis. It is predominantly characterized by excessive accumulation of extracellular matrix (ECM) components in the liver, caused by both markedly increased production and unbalanced degradation of connective tissue components. Hepatocytes and non-parenchymal cells (Ito cells, Kupffer cells, and sinusoidal endothelial cells) are all involved in the process. Understanding the pathogenic mechanism of hepatic fibrosis is essential for effective anti-fibrotic treatment. Hepatocyte necrosis is an initiating and sustaining stimulus in the process. Activated Kupffer cells in liver inflammation and their released bioactive factors (for example, cytokines, free oxygen species) play a modulating role for cells participating in the process. Ito cells (lipocytes, fat-storing cells (FSC)) are considered to be the main cell type for overproduction of ECM, and activation of these cells induces excessive matrix production at higher rates than other cell types in the liver (1, 2). Consequently, Ito cell activation is critical for initiation of the liver fibrogenesis, and whether any anti-fibrotic therapy can affect Ito cell activation and the consecutive expression of various matrix substances is an important aim for investigations.