Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: Current Knowledge of Pathogenesis and Therapeutics

Abstract

Cholangiopathies encompass various biliary diseases affecting the biliary epithelium, resulting in cholestasis, inflammation, fibrosis, and ultimately liver cirrhosis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the most important progressive cholangiopathies in adults. Much research has broadened the scope of disease biology to genetic risk, epigenetic changes, dysregulated mucosal immunity, altered biliary epithelial cell function, and dysbiosis, all of which interact and arise in the context of ill-defined environmental triggers. An in-depth understanding of the molecular pathogenesis of these cholestatic diseases will help clinicians better prevent and treat diseases. In this review, we focus on the main underlying mechanisms of disease initiation and progression, and novel targeted therapeutics beyond currently approved treatments.

Keywords: cholangiopathy; primary biliary cholangitis; primary sclerosing cholangitis.

Figure 1

The comparison between PBC and PSC. This is a figure highlighting the differences between two diseases. The picture is adapted from Gidwaney et al. [254] and Libre Pathology (https://librepathology.org, accessed on 28 April 2022). CoH: canals of Hering, PSC: primary sclerosing cholangitis, PBC: primary biliary cholangitis, IBD: inflammatory bowel disease, AMA: anti-mitochondrial antibody, AE2: anion exchanger 2, PDC-E2: pyruvate dehydrogenase complex, E2.