Current drugs in early development for treating hepatitis C virus-related hepatic fibrosis

More than 100 million people worldwide are infected with hepatitis C virus (HCV), which is responsible for chronic liver disease accompanied by progressive fibrosis of hepatic tissue, often leading to liver cirrhosis. Novel therapeutic options are able to clear the virus in almost all diagnosed patients. However, even after successful treatment, hepatic fibrosis may persist in many of them. There is no registered therapy specific for liver fibrosis, but numerous molecules are currently in development.

In this review, the authors look at drugs in early development for the treatment of HCV-related hepatic fibrosis. Their mechanism of action is based on the inhibition of hepatic inflammation, the modulation of cellular sources of extracellular matrix (ECM), the stimulation of ECM degradation and prevention of collagen crosslinking. Importantly, significant antifibrotic effects have been demonstrated with both IFN-based and IFN-free anti-HCV regimens.

Successful future therapy is likely to be based on sequential administration of drugs leading initially to HCV clearance, followed by treatment for the possible reversal of liver fibrosis. The primary consideration with clinical trials carried out in patients with advanced liver disease is safety. Indeed, the evaluation of anti-fibrotic therapy depends on reliable noninvasive techniques for quantification of liver fibrosis, such as transient or shear-wave elastography or serologic tests which are able to replace liver biopsy.