Abstract
Liver fibrosis is the pathological process of excessive extracellular matrix deposition after liver injury and is a precursor to cirrhosis, hepatocellular carcinoma (HCC). It is essentially a wound healing response to liver tissue damage. Numerous studies have shown that hepatic stellate cells play a critical role in this process, with various cells, cytokines, and signaling pathways engaged. Currently, the treatment targeting etiology is considered the most effective measure to prevent and treat liver fibrosis, but reversal fibrosis by elimination of the causative agent often occurs too slowly or too rarely to avoid life-threatening complications, especially in advanced fibrosis. Liver transplantation is the only treatment option in the end-stage, leaving us with an urgent need for new therapies. An in-depth understanding of the mechanisms of liver fibrosis could identify new targets for the treatment. Most of the drugs targeting critical cells and cytokines in the pathogenesis of liver fibrosis are still in pre-clinical trials and there are hardly any definitive anti-fibrotic chemical or biological drugs available for clinical use. In this review, we will summarize the pathogenesis of liver fibrosis, focusing on the role of key cells, associated mechanisms, and signaling pathways, and summarize various therapeutic measures or drugs that have been trialed in clinical practice or are in the research stage.
Highlights
Hepatic fibrosis is a universal pathological process that occurs in various types of chronic liver disease, including viral hepatitis, alcoholic hepatitis, fatty liver disease, nonalcoholic fatty liver disease (NAFLD), wilson’s disease, and cholangitis
Chronic damage to hepatocytes is the initiator of the fibrotic cascade, it induces the production of pro-fibrotic cytokines/growth factors (e.g., Tumour necrosis factor (TNF)-a, IL-6, transforming growth factor-β (TGF-β), and platelet-derived growth factor (PDGF)) indirectly through interactions with hepatic macrophages and natural killer (NK) cells
As research has progressed and understanding of the role of Hepatic stellate cells (HSCs) in disease has increased, we have found that HSCs have a role in promoting liver cell regeneration (Yang et al, 2008), which may be achieved mainly through the following mechanisms, secretion of cytokines that promote liver cell proliferation, promote the migration of stem cells to the liver, and promote the epithelial transformation of mesenchymal cells into hepatocytes
Summary
Liver fibrosis is the pathological process of excessive extracellular matrix deposition after liver injury and is a precursor to cirrhosis, hepatocellular carcinoma (HCC). It is essentially a wound healing response to liver tissue damage. Most of the drugs targeting critical cells and cytokines in the pathogenesis of liver fibrosis are still in pre-clinical trials and there are hardly any definitive anti-fibrotic chemical or biological drugs available for clinical use. We will summarize the pathogenesis of liver fibrosis, focusing on the role of key cells, associated mechanisms, and signaling pathways, and summarize various therapeutic measures or drugs that have been trialed in clinical practice or are in the research stage
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