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Liver fibrosis: Pathophysiology and clinical implications

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Abstract Liver fibrosis is a clinically significant finding that has major impacts on patient morbidity and mortality. The mechanism of fibrosis involves many different cellular pathways, but the major cell type involved appears to be hepatic stellate cells. Many liver diseases, including Hepatitis B, C, and fatty liver disease cause ongoing hepatocellular damage leading to liver fibrosis. No matter the cause of liver disease, liver‐related mortality increases exponentially with increasing fibrosis. The progression to cirrhosis brings more dramatic mortality and higher incidence of hepatocellular carcinoma. Fibrosis can also affect outcomes following liver transplantation in adult and pediatric patients and require retransplantation. Drugs exist to treat Hepatitis B and C that reverse fibrosis in patients with those viral diseases, but there are currently no therapies to directly treat liver fibrosis. Several mouse models of chronic liver diseases have been successfully reversed using novel drug targets with current therapies focusing mostly on prevention of myofibroblast activation. Further research in these areas could lead to development of drugs to treat fibrosis, which will have invaluable impact on patient survival. This article is categorized under: Translational, Genomic, and Systems Medicine > Translational Medicine Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
Pathophysiology of liver fibrosis. Chronic liver damage of different etiologies causes injured hepatocytes and LSEC to release proinflammatory and profibrogenic factors, which lead to chronic liver inflammation followed by activation of quiescent HSCs into collagen Types I and III‐producing myofibroblasts. As a result, fibrous scar accumulates into the liver impairing its normal functions (see text for details)
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Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
Translational, Genomic, and Systems Medicine > Translational Medicine

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