1,721,206 research outputs found
Functional anatomy of normal bile ducts.
No full textThe biliary tree is a complex network of conduits that begins with the canals of Hering and progressively merges into a system of interlobular, septal, and major ducts which then coalesce to form the extrahepatic bile ducts, which finally deliver bile to the gallbladder and to the intestine. The biliary epithelium shows a morphological heterogeneity that is strictly associated with a variety of functions performed at the different levels of the biliary tree. In addition to funneling bile into the intestine, cholangiocytes (the epithelial cells lining the bile ducts) are actively involved in bile production by performing both absorbitive and secretory functions. More recently, other important biological properties restricted to cholangiocytes lining the smaller bile ducts have been outlined, with regard to their plasticity (i.e., the ability to undergo limited phenotypic changes), reactivity (i.e., the ability to participate in the inflammatory reaction to liver damage), and ability to behave as liver progenitor cells. Functional interactions with other branching systems, such as nerve and vascular structures, are crucial in the modulation of the different cholangiocyte functions
Neural cell adhesion molecule and polysialic acid in ductular reaction: The puzzle is far from completed, but the picture is becoming more clear.
No full textInflammatory pathways and cholangiocarcioma risk mechanisms and prevention
No full textCholangiocarcinoma (CCA), a neoplasm burdened by a poor prognosis and currently lacking adequate therapeutic treatments, can originate at different levels of the biliary tree, in the intrahepatic, hilar, or extrahepatic area. The main risk factors for the development of CCA are the presence of chronic cholangiopathies of various etiology. To date, the most studied prodromal diseases of CCA are primary sclerosing cholangitis, Caroli's disease and fluke infestations, but other conditions, such as metabolic syndrome, nonalcoholic fatty liver disease and obesity, are emerging as associated with an increased risk of CCA development. In this review, we focused on the analysis of the pro-inflammatory mechanisms that induce the development of CCA and on the role of cells of the immune response in cholangiocarcinogenesis. In very recent times, these cellular mechanisms have been the subject of emerging studies aimed at verifying how the modulation of the inflammatory and immunological responses can have a therapeutic significance and how these can be used as therapeutic targets
Practice of adult liver transplantation in Italy. Recommendations of the Italian Association for the Study of the Liver (A.I.S.F.)
No full textLiver transplantation is an efficient procedure as performed in Italy, yet major differences are present in terms of practice. In an effort to facilitate an homogeneous practice of liver transplantation in Italy, the Italian Association for the Study of Liver Disease has instituted a Commission aimed at providing recommendations on non-urgent liver transplantation in adults, based on current evidence. This nation-wide commission which included experienced hepatologists, surgeons and pathologists with major interest in liver transplantation has drafted a final document in October 2004, approved by the Italian Association for the Study of Liver Governing Board, whose key arguments and main conclusions are summarised in the present paper. The Commission has made specific recommendations on the following topics: the current needs of liver transplantation in Italy; the indications to liver transplantation and re-liver transplantation, with special reference to controversial issues and the minimal listing criteria; the use of marginal donors and the need to optimise donor/recipient matching; the use of living donor liver transplantation; the management of the waiting list and the introduction of Model for End-Stage Liver Disease to define priorities; the clinical management of liver transplantation recipients and disease recurrence; the implementation of audits and outcome monitoring; the training of transplant surgeons and hepatologists and the requirements for Centre accreditation; the pathology of liver transplantation. (C) 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved
Development of the bile ducts: essentials for the clinical hepatologist.
No full textSeveral cholangiopathies result from a perturbation of developmental processes. Most of these cholangiopathies are characterised by the persistence of biliary structures with foetal configuration. Developmental processes are also relevant in acquired liver diseases, as liver repair mechanisms exploit a range of autocrine and paracrine signals transiently expressed in embryonic life. We briefly review the ontogenesis of the intra- and extrahepatic biliary tree, highlighting the morphogens, growth factors, and transcription factors that regulate biliary development, and the relationships between developing bile ducts and other branching biliary structures. Then, we discuss the ontogenetic mechanisms involved in liver repair, and how these mechanisms are recapitulated in ductular reaction, a common reparative response to many forms of biliary and hepatocellular damage. Finally, we discuss the pathogenic aspects of the most important primary cholangiopathies related to altered biliary development, i.e. polycystic and fibropolycystic liver diseases, Alagille syndrome
The balance between Notch/Wnt signaling regulates progenitor cells' commitment during liver repair: Mystery solved?
No full textDuring chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during chronic liver injury is promoted
Vascular biology of the biliary epithelium
No full textCholangiocytes are involved in a variety of processes essential for liver pathophysiology. To meet their demanding metabolic and functional needs, bile ducts are nourished by their own arterial supply, the peribiliary plexus. This capillary network originates from the hepatic artery and is strictly arranged around the intrahepatic bile ducts. Biliary and vascular structures are linked by a close anatomic and functional association necessary for liver development, normal organ physiology, and liver repair. This strong association is finely regulated by a range of angiogenic signals, enabling the cross talk between cholangiocytes and the different vascular cell types. This review will briefly illustrate the "vascular" properties of cholangiocytes, their underlying molecular mechanisms and the relevant pathophysiological settings
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