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Immunopathogenesis of Vanishing Bile Duct Syndromes
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
John M. Vierling, Marius Braun, Haimei Wang
Infection, toxicity, ischemia and neoplasia can instigate development of secondary sclerosing cholangitis.3 Evolving ductopenia and cholestasis, regardless of etiology, promote inflammation, biliary fibrosis and, ultimately, secondary biliary cirrhosis.8 Ductopenia and cholestasis increase LPS concentrations in the portal space, trigger innate immune activation of Kupffer cells and portal tract macrophages by LPS and possibly other bacterial cell wall products and induce macrophage secretion of proinflammatory cytokines IL-lβ, TNFα, IL-6, TGFα/β and leukotrienes.114 LPS inhibits HCO3™ secretion by BECs and perturbs cholehepatic cycling between BECs and peribiliary capillaries, resulting in potential retention of noxious molecules. In addition, TNFα reduces the integrity of BEC tight junctions, permitting bile to regurgitate into the peribiliary space. This milieu of proinflammatory cytokines and LPS stimulates BECs to secrete chemokines, cytokines and matrix metalloproteinases that recruit and activate leukocytes different from those mediating NSDC and destroy peribiliary matrix (Figs. 3 and 4). Thus, it is of interest to note matrix metalloproteinase 3 polymorphisms have been implicated in susceptibility and progression of PSC.115
The Gallbladder and Bile Ducts
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
Common symptoms include right upper quadrant discomfort, jaundice, pruritus, fever, fatigue and weight loss. Investigation reveals a cholestatic pattern to the liver function tests with elevation of the serum alkaline phosphatase and y-glu- tamyl transferase and smaller rises in the aminotransferases. Bilirubin values can be variable and may fluctuate. Imaging studies such as MRCP or ERCP may demonstrate stricturing and beading of the bile ducts (Figure67.37). A liver biopsy is helpful to confirm the diagnosis and may help guide therapy by excluding cirrhosis. The important differential diagnoses are secondary sclerosing cholangitis and cholangiocarcinoma. The latter may be very difficult to diagnose and a high index of suspicion is required especially in the setting of unexplained clinical deterioration.
Gastrointestinal and hepatobiliary
Published in Dave Maudgil, Anthony Watkinson, The Essential Guide to the New FRCR Part 2A and Radiology Boards, 2017
Dave Maudgil, Anthony Watkinson
Ampullary carcinoma or consequences of chemotherapy may alter bile flow and precipitate cholangitis. In most cases the cholangitis is non-suppurative and the patient is not septicaemic. The increased contrast enhancement is more marked in the extrahepatic portal vessels. Secondary sclerosing cholangitis is a complication of chronic cholangitis.
Risk factors and prognosis for recurrent primary sclerosing cholangitis after liver transplantation: a Nordic Multicentre Study
Published in Scandinavian Journal of Gastroenterology, 2018
Lina Lindström, Kristin K. Jørgensen, Kirsten M. Boberg, Maria Castedal, Allan Rasmussen, Andreas Arendtsen Rostved, Helena Isoniemi, Matteo Bottai, Annika Bergquist
The diagnosis of rPSC was made when cholangiography findings consistent with PSC were present in the absence of defined causes of secondary sclerosing cholangitis (hepatic artery thrombosis/stenosis, established ductopenic rejection, anastomotic biliary strictures alone, non-anastomotic strictures occurring before day 90 post LTx, ABO incompatibility between donor and recipient) [19].
Anti-programmed cell death-1 and anti-programmed cell death ligand-1 immune-related liver diseases: from clinical pivotal studies to real-life experience
Published in Expert Opinion on Biological Therapy, 2020
Giovanni Vitale, Giuseppe Lamberti, Francesca Comito, Vincenzo Di Nunno, Francesco Massari, Maria Cristina Morelli, Andrea Ardizzoni, Francesco Gelsomino
Secondary sclerosing cholangitis had been previously described following either transarterial infusion of chemotherapeutic agents, due to an ischemic injury to the biliary tract, or use of certain drugs, such as amoxicillin-clavulanate, sevoflurane, amiodarone, infliximab, 6-mercaptopurine, gabapentin, venlafaxine and atorvastatin [53].
Biological therapies in patients with liver disease: are they really lifesavers?
Published in Expert Opinion on Biological Therapy, 2022
Giovanni Vitale, Stefano Gitto, Claudia Campani, Laura Turco, Anna Baldan, Fabio Marra, Maria Cristina Morelli
Secondary sclerosing cholangitis presents similar multifocal biliary strictures mainly due to long-term biliary obstruction, infections, IgG4-associated cholangitis, intra-arterial chemotherapy, ischemic cholangitis portal hypertensive biliopathy, ending in the destruction of bile ducts, and secondary biliary cirrhosis [21].