Ulrich Beuers1, Luca Maroni, Ronald O Elferink. 1. Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. u.h.beuers@amc.uva.nl
Abstract
PURPOSE OF REVIEW: To critically review most recent experimental evidence for the protective action of biliary HCO(3)(-) secretion against bile acid-induced bile duct damage and development of fibrosing cholangiopathy in humans and experimental animals. RECENT FINDINGS: Studies in human cholangiocytes in vitro indicate that a biliary HCO(3)(-) umbrella protects against bile acid-induced cholangiocyte damage and apoptosis in humans. The Cl(-)/HCO(3)(-) exchanger, AE2, and an intact biliary glycocalyx appear crucial for its stability. Related studies with experimental animal models in vivo have to be interpreted with caution as humans and mice differ not only with regard to bile salt pool, but also their expression patterns of transport proteins and signalling molecules. SUMMARY: Adequate biliary HCO(3)(-) secretion may protect against bile salt-induced cholangiopathies. Future therapeutic strategies in biliary diseases will aim at stabilizing the biliary HCO(3)(-) umbrella.
PURPOSE OF REVIEW: To critically review most recent experimental evidence for the protective action of biliary HCO(3)(-) secretion against bile acid-induced bile duct damage and development of fibrosing cholangiopathy in humans and experimental animals. RECENT FINDINGS: Studies in human cholangiocytes in vitro indicate that a biliary HCO(3)(-) umbrella protects against bile acid-induced cholangiocyte damage and apoptosis in humans. The Cl(-)/HCO(3)(-) exchanger, AE2, and an intact biliary glycocalyx appear crucial for its stability. Related studies with experimental animal models in vivo have to be interpreted with caution as humans and mice differ not only with regard to bile salt pool, but also their expression patterns of transport proteins and signalling molecules. SUMMARY: Adequate biliary HCO(3)(-) secretion may protect against bile salt-induced cholangiopathies. Future therapeutic strategies in biliary diseases will aim at stabilizing the biliary HCO(3)(-) umbrella.
Authors: Rohit Gaurav; Niroshan Atulugama; Lisa Swift; Andrew J Butler; Sara Upponi; Rebecca Brais; Michael Allison; Christopher J E Watson Journal: Liver Transpl Date: 2020-08 Impact factor: 5.799