Hepatology Xagena

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New strategy for the treatment of liver fibrosis: CB1 cannabinoid receptor antagonism

Hepatic fibrosis, the common response associated with chronic liver diseases, ultimately leads to cirrhosis.
Researchers showed that activation of hepatic cannabinoid CB2 receptors limits progression of experimental liver fibrosis. They also found that during the course of chronic hepatitis C, daily cannabis use is an independent predictor of fibrosis progression.
Overall, these results suggest that endocannabinoids may drive both CB2-mediated antifibrogenic effects and CB2-independent profibrogenic effects.

Researchers, at Hopital Henri Mondor - Creteil ( France ), investigated whether activation of cannabinoid CB1 receptors ( encoded by Cnr1 ) promotes progression of fibrosis.
CB1 receptors were highly induced in human cirrhotic samples and in liver fibrogenic cells.

Treatment with the CB1 receptor antagonist SR141716A decreased the wound-healing response to acute liver injury and inhibited progression of fibrosis in three models of chronic liver injury.
Similar changes were seen in Cnr1-/- mice as compared to wild-type mice.

Genetic or pharmacological inactivation of CB1 receptors decreased fibrogenesis by lowering hepatic transforming growth factor ( TGF )-beta1 and reducing accumulation of fibrogenic cells in the liver after apoptosis and growth inhibition of hepatic myofibroblasts.

The study has shown that CB1 receptor antagonists hold promise for the treatment of liver fibrosis.

Source: Nature Medicine, 2006