Do we need targeting to specific liver cells? Uptake of drugs in the liver is usually high. While most existing drugs are not cellspecific at all, they are effective. However, uptake by fibrogenic cells in the fibrotic liver is usually low and off-target effects can be high, eg, 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 (ie a situation similar to the clinical practice). To date, no antifibrotic drug has reached the clinic.

Some drugs are intrinsically targeted to the fibrogenic process due to their (receptor) specificity. Examples are PDGFRb or integrin aVb6 antagonists/blocking antibodies, or liposomal aptamers or siRNA against procollagen I, but even here delivery to their target cells in advanced fibrotic livers may be limited.