Targeted therapy of liver fibrosis/cirrhosis and its complications

Do we need targeting to specific liver cells? Uptake of drugs in the liver is usually high. While most existing drugs are not cell-specific at all, they are effective. However, uptake by fibrogenic cells in the fibrotic liver is usually low and off-target effects can be high, e.g., due to compromised hepatic metabolism and excretion. Therefore, most experimental drugs are not effective at the preclinical level when they are administered in animals with advanced and established fibrosis (i.e. a situation similar to the clinical practice).