The challenges of primary biliary cholangitis: What is new and what needs to be done

Abstract

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Hepatobiliary acid-base homeostasis: Insights from analogous secretory epithelia

“…Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) as model cholestatic liver diseases affect small intrahepatic and larger intra-and extrahepatic bile ducts, respectively [1,2]. Notably, impaired HCO 3 secretion has been described in PBC two decades ago putatively caused by microRNA-506-dependent defective expression of the Cl -/ HCO 3 exchanger AE2 [3,4].…”

Changes in Microbiota and Metabolites Are Associated With Effects of Bile Acid Sequestrant on Icteric Primary Biliary Cholangitis

“…In addition to the decrease of total serum BAs upon treatment, serum BA pro ling showed a signi cant shift towards a more hydrophilic con guration. Hydrophobic bile acids are known to elicit apoptosis and senescence of biliary epithelial cells [1] . Sequestration of intestinal BAs downregulated the levels of FGF19, leading to derepression of CYP7A1 and upregulation of BA synthesis, which is in part evidenced by the reduced levels of cholesterol in our PBC cohort.…”

“…Primary biliary cholangitis (PBC) is an important but uncommon autoimmune liver disease characterized by the presence of antimichondrial antibodies (AMA) and progressive destruction of interlobular bile ducts [1] . Ursodeoxycholic acid (UDCA), a choleretic bile acid, is successful in approximately two thirds of early-stage PBC patients and improves life expectancy without additional therapies [2,3] .…”

“…Emerging evidence suggests a critical role for the excessive toxic bile acids (BAs) and gut dysbiosis in the pathogenesis of PBC. [1,3] Interactions between bile acids and gut microbiome have been well estabilished. By acting on farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), BAs are involved in multiple signaling pathways, including metabolism, brosis and immune homeostasis [4,5] .…”

The Emerging Role of Macrophages in Chronic Cholangiopathies Featuring Biliary Fibrosis: An Attractive Therapeutic Target for Orphan Diseases

“…To date, only a few pharmacological therapies have been proven to be effective and only in limited pathology conditions (urosodeoxycholic acid, obeticholic acid, and bezafibrate in primary biliary cholangitis), while the vast majority of cholangiopathies are still orphan. Liver transplantation remains the only option when the disease is advanced (8)(9)(10). Major efforts for developing effective therapeutic strategies in cholangiopathies should be devoted to halt biliary fibrogenesis (4,11).…”