• liver
• fibrosis
• liver cirrhosis

Despite major therapeutic advances to treat patients with chronic liver diseases, one target remains elusive in hepatology and this is the most important one: liver fibrosis. We can cure patients from chronic hepatitis C; we can vaccinate against hepatitis B virus and control chronic hepatitis B; we have new drugs to treat cholestatic liver diseases and several lines of treatment to treat patients with hepatocellular carcinoma. But the process driving the prognosis of patients with chronic liver disease and the scarring process of the hepatic parenchyma are beyond our armamentarium. Hepatic fibrosing is a highly complex process which has been extensively studied in patients and in great details in animal models. Activation of quiescent hepatic stellate cells into α-smooth muscle actin (α-SMA)-positive myofibroblasts is a key mechanism since once activated, these cells secrete collagens and other matrix components participating actively in the scarring process. Numerous potential druggable mechanisms have been investigated and pharmacologically tested with success in animal models. However, despite great interest from the academic community and from the pharma only a few drugs have been tested in clinical trials with disappointing results.

Salhab et al conducted an elegant series of experiments studying an unlikely target to treat hepatic fibrosis namely the Na⁺/taurocholate cotransporting polypeptide (NTCP).1 NTCP was the first bile acid transporter to be cloned. This feat was achieved in 1989 by Hagenbruch et al when he worked in the laboratory of the late P. Meier-Abt in Zürich using an expression cloning strategy.2 NTCP is expressed on the basolateral membrane of hepatocytes allowing the hepatocellular uptake …