Liver Fibrosis

Liver fibrosis is a common outcome of a number of chronic liver diseases often resulting from repeated damage to the liver resulting in accumulation of collagen and other extracellular matrix proteins.  This buildup can result in liver failure, cirrhosis, and portal hypertension.   While a number of treatments exist, there is still an unmet need for drugs that target the reversal of fibrosis. 

CCl4-Induced Liver Fibrosis

Carbon tetrachloride (CCl4) is a hepato-toxic agent, that when administered chronically (2x/week over 8-16 weeks), can lead to liver fibrosis, first developing in pericentral areas and then forming bridges between central areas and later between central and portal areas.  Animals can be evaluated at different timepoints to detect liver disease as levels of serum ALT, ALB and ALP are elevated beginning at 8 weeks.  Liver pathology is assessed in H&E and Picrosirius red-stained sections and fibrosis scores are determined. 

Study Design Table

Model Description Duration Endpoints
CCl4-induced liver fibrosis CCl4 is administered 2x/week IP 8-16 Weeks Body Weight, serum liver enzyme analysis, collagen content, histopathology: fibrosis scoring and quantification

 

Increasing levels of fibrosis are observed in the liver of Balb/c mice  following chronic administration of CCl4.  Bridging fibrosis is most severe following 16 weeks of CCl4 administration.
Severity of increasing levels of observed fibrosis were semi quantitatively scored by a board-certified veterinary pathologist.  Scores: 0=no increased collagen (normal liver); 1=minimal; 2=mild; 3=moderate; 4=marked; 5=severe/cirrhotic
Serum levels Alanine Aminotransferase (ALT), Albumin (ALB), and Alkaline Phosphatase (ALP) were assessed in control and diseased animals
Wet liver weights were recorded at sacrifice
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