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Translating an understanding of the pathogenesis of hepatic fibrosis to novel therapies

, : Translating an understanding of the pathogenesis of hepatic fibrosis to novel therapies. Clinical Gastroenterology and Hepatology 11(3): 224-31.E1-5

The response to injury is one of wound healing and fibrogenesis, which ultimately leads to fibrosis. The fibrogenic response to injury is a generalized one across virtually all organ systems. In the liver, the injury response, typically occuring over a prolonged period of time, leads to cirrhosis (although it should be pointed out that not all patients with liver injury develop cirrhosis). The fact that many different diseases result in cirrhosis suggests a common pathogenesis. The study of hepatic fibrogenesis over the past 2 decades has been remarkably active, leading to a considerable understanding of this process. It has been clearly demonstrated that the hepatic stellate cell is a central component in the fibrogenic process. It has also been recognized that other effector cells are important in the fibrogenic process, including resident fibroblasts, bone marrow derived cells, fibrocytes, and even perhaps cells derived from epithelial cells (i.e., through epithelial to mesenchymal transition or EMT). A key aspect of the biology of fibrogenesis is that the fibrogenic process is dynamic; thus, even advanced fibrosis (or cirrhosis) is reversible. Together, an understanding of the cellular basis for liver fibrogenesis, along with multiple aspects of the basic pathogenesis of fibrosis, have highlighted many exciting potential therapeutic opportunities. Thus, while the most effective anti-fibrotic therapy is treatment of the underlying disease, in situations in which this not possible, specific anti-fibrotic therapy is likely to not only become feasible, but will soon become a reality. The goal of this review is to highlight the mechanisms underlying fibrogenesis that may be translated into future anti-fibrotic therapies and to review the current state of clinical development.

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Accession: 036708067

PMID: 23305825

DOI: 10.1016/j.cgh.2013.01.005

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