Fibrosing cholangiopathies Insights in clinical aspects and novel therapeutic approaches

Fibrosing cholangiopathies represent chronic liver diseases in which injury of the cholangiocyte and, thereby, the biliary tree is a disease-defining feature. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the most prevalent fibrosing cholangiopathies. Both diseases are characterized by inflammation and fibrosis of small intrahepatic (PBC) or larger intra- and/or extrahepatic (PSC) bile ducts, however the exact pathogenesis has not been clarified. Other examples of fibrosing cholangiopathies are immunoglobin G4 (IgG4)-related cholangitis and ATP binding cassette B4 (ABCB4) deficiency-related cholangitis, both forms of secondary sclerosing cholangitis. These diseases are characterized by cholestasis, which implies impaired flow (stasis) of bile (chole). Cholestasis has several levels of origin: a hepatocellular origin, a cholangiocellular origin or obstruction / compression of the bile ducts due to intra- or extraluminal processes. This thesis addresses different aspects of cholestasis-associated diseases: chapter 2) novel therapies of chronic cholestatic liver diseases, chapter 3) the results of the FITCH trial, showing that bezafibrate is superior to placebo in treatment of moderate to severe cholestasis-associated pruritus in patients with fibrosing cholangiopathies, chapter 4) an overview of the current literature regarding UDCA treatment during pregnancy and lactation in which we conclude that administration of UDCA appears safe during pregnancy and lactation, chapter 5) the importance of strictly obeying criteria for intrahepatic cholestasis of pregnancy in trials, chapter 6) the effect of obeticholic acid on bile acid profile in patients in comparison to healthy volunteers, chapter 7) a diminished quality of life in carriers of ABCB4 gene variants and chapter 8) poor discrimination of IgG4-related disease from pancreatobiliary cancer through blood IgG4/IgG RNA ratio by qPCR.