Cholestatic Liver Disease: Current Treatment Strategies and New Therapeutic Agents

Abstract

Cholestatic liver disease is a disease that causes liver damage and fibrosis owing to bile stasis. It is represented by primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), but the pathophysiological pathways that cause bile stasis in both diseases are different. The pathogenesis of the disease is still unclear, although autoimmune mechanisms have been postulated and partially elucidated. Although the disease may progress slowly with only mild liver dysfunction, it may progress to liver cirrhosis or liver failure, which require liver transplantation. As a medical treatment, ursodeoxycholic acid is widely used for PBC and has proved to be very effective against disease progression in cases of PBC. On the other hand, its efficacy is limited in cases of PSC, and the research and development of various drugs are underway. Furthermore, the clinical course of both diseases is quite variable, making the design of clinical trials fairly difficult. In this review, we present the general natural history of PBC and PSC, and provide information on the latest drug therapies currently available and those that are under investigation.

Fig. 1

Clinical picture of PBC and PSC. a Cholangiography of the PSC by ERCP. There are multiple stenoses in the bile duct (yellow arrowhead, diverticulum-like outpunching; orange arrowhead, band-like stricture). b Histopathology of PSC obtained by liver biopsy. There is “onion-skin fibrosis” around intrahepatic small bile ducts. c Histopathology of PBC obtained by liver biopsy. The findings of chronic non-suppurative destructive cholangitis. ERCP endoscopic retrograde cholangiopancreatography, PBC primary biliary cholangitis, PSC primary sclerosing cholangitis

Fig. 2

Pharmacological treatment for cholestatic liver disease. FGF fibroblast growth factor, FGF-R fibroblast growth factor receptor, FXR farnesoid X receptor, OCA obeticholic acid, PPAR peroxisome proliferator-activated receptor, TNF tumor necrosis factor, UDCA ursodeoxycholic acid