Caspase Inhibitors in Chronic HCV
Caspases are an attractive target mechanism in the setting of HCV:
- Caspases are activated in human biopsy specimens of chronic HCV patients.
- Activation precedes morphological evidence of cell death.
- Levels of caspase activation in hepatocytes correlate with histological grade of disease.
- ~4X more apoptotic cells are detected in HCV-infected liver tissue compared to control.
- Caspase inhibitors protect hepatocytes from death signals during HCV infection and organ stress.
- Apoptotic markers are decreased in HCV patients after treatment with caspase inhibitors.
In the clinic, the ultimate result of caspase inhibition could be an overall reduction in the negative consequences of the host response to the virus infection (i.e., reduction in inflammation, apoptosis and fibrosis). In HCV infected patients, emricasan treatment could lead to rapid and sustained reduction in biochemical markers of liver disease (aminotransferases) with a corresponding reduction in liver damage (improvement in liver histology) as cell death mechanisms are controlled.