cholestasis

Summary

Summary: Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).

Top Publications

  1. ncbi Cholestasis and cholestatic syndromes
    Gideon M Hirschfield
    Liver Centre, Toronto Western Hospital, Department of Medicine, University of Toronto, Toronto, Canada
    Curr Opin Gastroenterol 25:175-9. 2009
  2. ncbi Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver
    Anne T Nies
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Hepatology 50:1227-40. 2009
  3. ncbi Mechanisms of disease: update on the molecular etiology and fundamentals of parenteral nutrition associated cholestasis
    Beth A Carter
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine, Houston, TX 77030, USA
    Nat Clin Pract Gastroenterol Hepatol 4:277-87. 2007
  4. pmc Bile-acid-induced cell injury and protection
    Maria J Perez
    Department of Biochemistry and Molecular Biology Campus Miguel de Unamuno E D 129, Salamanca, Spain
    World J Gastroenterol 15:1677-89. 2009
  5. pmc Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype
    Shadi Abu-Hayyeh
    Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
    Hepatology 57:716-26. 2013
  6. pmc The role of inflammation in cholestasis: clinical and basic aspects
    Astrid Kosters
    Texas Children s Liver Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
    Semin Liver Dis 30:186-94. 2010
  7. ncbi Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediators
    Hernan E Gonzalez
    Departamento de Ciencias Fisiologicas, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile
    Am J Physiol Gastrointest Liver Physiol 282:G991-G1001. 2002
  8. ncbi CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice
    Martin Wagner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine, Medical University Graz, Auenbruggerplatz 15, A 8036 Graz, Austria
    Hepatology 42:420-30. 2005
  9. ncbi Mechanisms of disease: mechanisms and clinical implications of cholestasis in sepsis
    Andreas Geier
    Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Aachen University, Germany
    Nat Clin Pract Gastroenterol Hepatol 3:574-85. 2006
  10. ncbi Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis
    Hiroshi Uchinami
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Hepatology 44:420-9. 2006

Detail Information

Publications363 found, 100 shown here

  1. ncbi Cholestasis and cholestatic syndromes
    Gideon M Hirschfield
    Liver Centre, Toronto Western Hospital, Department of Medicine, University of Toronto, Toronto, Canada
    Curr Opin Gastroenterol 25:175-9. 2009
    ..Cholestatic liver injury is encountered across a wide variety of clinical scenarios ranging from toxin-induced, genetic, to autoimmune in nature. This review summarizes recent findings from what is a burgeoning clinical field...
  2. ncbi Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver
    Anne T Nies
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Hepatology 50:1227-40. 2009
    ..0001), and four variants in OCT3 (rs2292334, rs2048327, rs1810126, rs3088442) were associated with reduced OCT3 mRNA levels (P = 0.03)...
  3. ncbi Mechanisms of disease: update on the molecular etiology and fundamentals of parenteral nutrition associated cholestasis
    Beth A Carter
    Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Baylor College of Medicine, Houston, TX 77030, USA
    Nat Clin Pract Gastroenterol Hepatol 4:277-87. 2007
    ..its association with hepatic complications described, the precise etiology of parenteral nutrition associated cholestasis (PNAC) remains a mystery; however, our understanding of the molecular components that contribute to PNAC has ..
  4. pmc Bile-acid-induced cell injury and protection
    Maria J Perez
    Department of Biochemistry and Molecular Biology Campus Miguel de Unamuno E D 129, Salamanca, Spain
    World J Gastroenterol 15:1677-89. 2009
    ..Other natural BAs or their derivatives, such as cholyl-N-methylglycine or cholylsarcosine, have also aroused pharmacological interest owing to their protective properties...
  5. pmc Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype
    Shadi Abu-Hayyeh
    Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
    Hepatology 57:716-26. 2013
    Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy-specific liver disease and is associated with an increased risk of adverse fetal outcomes, including preterm labor and intrauterine death...
  6. pmc The role of inflammation in cholestasis: clinical and basic aspects
    Astrid Kosters
    Texas Children s Liver Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
    Semin Liver Dis 30:186-94. 2010
    ..Disruption and dysregulation of this excretory pathway result in cholestasis, leading to the intrahepatic accumulation of bile acids and other toxic compounds with progression of liver ..
  7. ncbi Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediators
    Hernan E Gonzalez
    Departamento de Ciencias Fisiologicas, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile
    Am J Physiol Gastrointest Liver Physiol 282:G991-G1001. 2002
    Hepatocyte gap junction proteins, connexins (Cxs) 26 and 32, are downregulated during obstructive cholestasis (OC) and lipopolysaccharide hepatocellular cholestasis (LPS-HC)...
  8. ncbi CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice
    Martin Wagner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine, Medical University Graz, Auenbruggerplatz 15, A 8036 Graz, Austria
    Hepatology 42:420-30. 2005
    ..enzymes and alternative excretory pumps may limit hepatocellular accumulation of toxic biliary compounds in cholestasis. Because the nuclear xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) ..
  9. ncbi Mechanisms of disease: mechanisms and clinical implications of cholestasis in sepsis
    Andreas Geier
    Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Aachen University, Germany
    Nat Clin Pract Gastroenterol Hepatol 3:574-85. 2006
    b>Cholestasis is a common complication in patients with extrahepatic bacterial infection and sepsis. This article gives a comprehensive overview of the molecular and cellular mechanisms of sepsis-associated cholestasis...
  10. ncbi Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis
    Hiroshi Uchinami
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Hepatology 44:420-9. 2006
    b>Cholestasis occurs in a variety of clinical settings and often results in liver injury and secondary biliary fibrosis. Several matrix metalloproteinases (MMPs) are upregulated in the liver during cholestasis...
  11. ncbi Bile salt transporters: molecular characterization, function, and regulation
    Michael Trauner
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Karl Franzens University, School of Medicine, Graz, Austria
    Physiol Rev 83:633-71. 2003
    ..During bile secretory failure (cholestasis), bile salt transport proteins undergo adaptive responses that serve to protect the liver from bile salt ..
  12. ncbi Progressive familial intrahepatic cholestasis, type 1, is associated with decreased farnesoid X receptor activity
    Frank Chen
    Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Gastroenterology 126:756-64. 2004
    The mechanisms by which mutations in the familial intrahepatic cholestasis-1 gene cause Byler's disease (progressive familial intrahepatic cholestasis type 1) are unknown.
  13. ncbi Parenteral nutrition-associated liver complications in children
    Imad F Btaiche
    Department of Pharmacy Services, University of Michigan Health System, Ann Arbor 48109 0008, USA
    Pharmacotherapy 22:188-211. 2002
    ..nutrition is associated with complications affecting the hepatobiliary system, such as cholelithiasis, cholestasis, and steatosis...
  14. ncbi Role of nuclear receptors for bile acid metabolism, bile secretion, cholestasis, and gallstone disease
    Thierry Claudel
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Austria
    Biochim Biophys Acta 1812:867-78. 2011
    ..Hereditary and acquired alterations of NRs contribute to our understanding of the pathogenesis of cholestasis and gallstone disease. Moreover, NRs may represent attractive drug targets for these disorders...
  15. ncbi "Let there be bile"--understanding hepatic injury in cholestasis
    Ronald J Sokol
    Department of Pediatrics, Pediatric Liver Center and Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine and The Children s Hospital, Denver, CO 80218 1088 USA
    J Pediatr Gastroenterol Nutr 43:S4-9. 2006
    ..the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids in cholestasis. Steatocholestasis is the combined presence of hepatic steatosis and cholestasis, common in genetic causes of ..
  16. ncbi Oxidative stress plays a major role in chlorpromazine-induced cholestasis in human HepaRG cells
    Sebastien Antherieu
    INSERM UMR991, Liver Metabolisms and Cancer, Rennes, France
    Hepatology 57:1518-29. 2013
    Drugs induce cholestasis by diverse and still poorly understood mechanisms in humans...
  17. ncbi Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver
    U Beuers
    Department of Medicine II, Klinikum Grosshadern, University of Munich, Munich, Germany
    Hepatology 33:1206-16. 2001
    ..taurine-conjugated UDCA (TUDCA) was studied in the experimental model of taurolithocholic acid (TLCA)-induced cholestasis on bile flow, hepatobiliary exocytosis, distribution of PKC isoforms, and density of the apical conjugate ..
  18. pmc Bile acid transporters and regulatory nuclear receptors in the liver and beyond
    Emina Halilbasic
    Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria
    J Hepatol 58:155-68. 2013
    ..defects of BA transporters are involved in the pathogenesis of several hepatobiliary disorders including cholestasis, gallstones, fatty liver disease and liver cancer, but also play a role in intestinal and metabolic disorders ..
  19. ncbi Meta-analysis of randomized trials comparing the patency of covered and uncovered self-expandable metal stents for palliation of distal malignant bile duct obstruction
    Atif Saleem
    Department of Internal Medicine, Mayo Clinic, College of Medicine, Rochester, Minnesota, USA
    Gastrointest Endosc 74:321-327.e1-3. 2011
    ..Self-expandable metal stents (SEMSs) are used for palliation of malignant biliary obstruction...
  20. ncbi TNFalpha is required for cholestasis-induced liver fibrosis in the mouse
    Erwin Gabele
    Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Biochem Biophys Res Commun 378:348-53. 2009
    ..Thus, our data indicate that TNFalpha induces hepatotoxicity and promotes fibrogenesis in the BDL model...
  21. ncbi Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents
    James L Boyer
    Liver Center, Yale University School of Medicine, New Haven, CT 06520, USA
    Am J Physiol Gastrointest Liver Physiol 290:G1124-30. 2006
    ..These results indicate that expression of Ostalpha and Ostbeta are highly regulated in response to cholestasis and that this response is dependent on the FXR bile acid receptor.
  22. ncbi Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions
    Andreas E Kremer
    Tytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Hepatology 56:1391-400. 2012
    ..In this study, we highlight that increased serum ATX levels are specific for pruritus of cholestasis, but not pruritus of uremia, Hodgkin's disease, or atopic dermatitis...
  23. ncbi Hepatobiliary transporters and drug-induced cholestasis
    Christiane Pauli-Magnus
    Division of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland
    Hepatology 44:778-87. 2006
    ..by pre-existing hepatic disease and genetic factors, which contribute to the development of drug-induced cholestasis in susceptible individuals...
  24. pmc An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids
    W Xie
    Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 98:3375-80. 2001
    ..step in the metabolism and excretion of bile acids and is necessary to avoid pathologic conditions such as cholestasis and liver damage...
  25. ncbi Selective activation of nuclear bile acid receptor FXR in the intestine protects mice against cholestasis
    Salvatore Modica
    Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
    Gastroenterology 142:355-65.e1-4. 2012
    b>Cholestasis is a liver disorder characterized by impaired bile flow, reduction of bile acids (BAs) in the intestine, and retention of BAs in the liver. The farnesoid X receptor (FXR) is the transcriptional regulator of BA homeostasis...
  26. ncbi Phosphoinositide 3-kinase/protein kinase B signaling pathway is involved in estradiol 17β-D-glucuronide-induced cholestasis: complementarity with classical protein kinase C
    Andrea C Boaglio
    Institute of Experimental Physiology, National Scientific and Technical Research Council University of Rosario, Rosario, Argentina
    Hepatology 52:1465-76. 2010
    ..We assessed whether phosphoinositide 3-kinase (PI3K) is involved in E(2)17G-induced cholestasis. E(2)17G activated PI3K according to an assessment of the phosphorylation of the final PI3K effector, protein ..
  27. ncbi Temporary placement of fully covered self-expandable metal stents in benign biliary strictures: midterm evaluation (with video)
    Anshu Mahajan
    Digestive Health Center, University of Virginia Health System, Charlottesville, Virginia 22908 0708, USA
    Gastrointest Endosc 70:303-9. 2009
    ..Recently, fully covered self-expandable metal stents (CSEMSs) with anchoring fins have become available...
  28. ncbi Endoscopic bilateral metal stent placement for advanced hilar cholangiocarcinoma: a pilot study of a newly designed Y stent
    Jung Hyun Lee
    Department of Internal Medicine, Pusan National University College of Medicine, Seo Gu, Busan, Korea
    Gastrointest Endosc 66:364-9. 2007
    ....
  29. ncbi Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations
    Gernot Zollner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Austria, and Karolinska University Hospital Huddinge, Stockholm, Sweden
    Mol Pharm 3:231-51. 2006
    b>Cholestasis results in intrahepatic accumulation of cytotoxic bile acids which cause liver injury ultimately leading to biliary fibrosis and cirrhosis...
  30. pmc Obstruction of extrahepatic bile ducts by lymphocytes is regulated by IFN-gamma in experimental biliary atresia
    Pranavkumar Shivakumar
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Ohio 45229 3039, USA
    J Clin Invest 114:322-9. 2004
    ..Thus, IFN-gamma-driven obstruction of bile ducts is a key pathogenic mechanism of disease and may constitute a therapeutic target to block disease progression in patients with biliary atresia...
  31. pmc Effector role of neonatal hepatic CD8+ lymphocytes in epithelial injury and autoimmunity in experimental biliary atresia
    Pranavkumar Shivakumar
    Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 3039, USA
    Gastroenterology 133:268-77. 2007
    ..Here, we investigate this question by examining the role of T lymphocytes in the destruction of extrahepatic bile ducts of neonatal mice using an experimental model of biliary atresia...
  32. pmc A prospective randomised study of "covered" versus "uncovered" diamond stents for the management of distal malignant biliary obstruction
    H Isayama
    Department of Gastroenterology, University of Tokyo, Tokyo, Japan
    Gut 53:729-34. 2004
    ..Covered self-expandable metal stents (EMS) were recently developed to overcome tumour ingrowth in conventional EMS. However, supporting evidence for the efficacy of covered EMS is lacking...
  33. ncbi CHOP deficiency attenuates cholestasis-induced liver fibrosis by reduction of hepatocyte injury
    Nobuyuki Tamaki
    Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606 8507, Japan
    Am J Physiol Gastrointest Liver Physiol 294:G498-505. 2008
    ..In conclusion, cholestasis induces CHOP-mediated ER stress and triggers hepatocyte cell death, and CHOP deficiency attenuates this cell ..
  34. ncbi LPS signaling enhances hepatic fibrogenesis caused by experimental cholestasis in mice
    Fuyumi Isayama
    Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina, Chapel Hill, 27599, USA
    Am J Physiol Gastrointest Liver Physiol 290:G1318-28. 2006
    ..to test the hypothesis that LPS signaling through CD14 contributes to hepatic fibrosis caused by experimental cholestasis. Wild-type mice and CD14 knockout mice (CD14(-/-)) underwent sham operation or bile duct ligation and were ..
  35. ncbi Loss of orphan receptor small heterodimer partner sensitizes mice to liver injury from obstructive cholestasis
    Young Joo Park
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Hepatology 47:1578-86. 2008
    ..Shp(-/-) mice show increased sensitivity in this model of acute obstructive cholestasis, with greater numbers of bile infarcts and higher mortality than wild-type C57BL/6 mice...
  36. pmc Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis
    Yaping Liu
    Nuclear Receptor Functional Analysis, High Thruput Biology, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
    J Clin Invest 112:1678-87. 2003
    ..agonist GW4064 could protect against cholestatic liver damage in rat models of extrahepatic and intrahepatic cholestasis. In the bile duct-ligation and alpha-naphthylisothiocyanate models of cholestasis, GW4064 treatment resulted in ..
  37. ncbi Cholestasis: human disease and experimental animal models
    Emilio Alberto Rodríguez-Garay
    Instituto de Fisiologia Experimental, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Universidad Nacional de Rosario, Rosario, Argentina
    Ann Hepatol 2:150-8. 2003
    b>Cholestasis may result from a failure in bile secretion in hepatocytes or ductular cells, or from a blockade to the free bile flow. Human cholestasis may be induced by many drugs, being antibiotics the more common...
  38. ncbi Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis
    Stefano Fiorucci
    Gastroenterologia ed Epatologia, Policlinico Monteluce, Perugia, Italy
    J Pharmacol Exp Ther 313:604-12. 2005
    ..acid (6-ECDCA or INT-747), a semisynthetic bile acid derivative and potent FXR ligand, in a model of cholestasis induced by 5-day administration of 17alpha-ethynylestradiol (E(2)17alpha) to rats...
  39. ncbi Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis
    Chien Yi Chen
    Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, No 7 Chung Shan South Road, Taipei 100, Taiwan
    J Pediatr 145:317-21. 2004
    To determine the effect of ursodeoxycholic acid (UDCA) in very-low-birth-weight (VLBW) infants with parenteral nutrition-associated cholestasis (PNAC).
  40. ncbi Soybean oil fat emulsion to prevent TPN-induced liver damage: possible molecular mechanisms and clinical implications
    Masuhiro Nishimura
    Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc, Naruto, Tokushima, Japan
    Biol Pharm Bull 29:855-62. 2006
    Long-term total parenteral nutrition (TPN) is known to be associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally...
  41. ncbi Facial features in Alagille syndrome: specific or cholestasis facies?
    Binita M Kamath
    Division of Gastroenterology and Nutrition, The Children s Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Am J Med Genet 112:163-70. 2002
    Alagille syndrome is a complex multisystem disorder characterized by bile duct paucity, cholestasis, cardiac defects, vertebral anomalies, ophthalmologic changes, and facial dysmorphism...
  42. ncbi Polyurethane-covered metal stent for management of distal malignant biliary obstruction
    Hiroyuki Isayama
    Department of Gastroenterology, Department of Endoscopy and Endoscopic Surgery, Faculty of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Gastrointest Endosc 55:366-70. 2002
    ..The efficacy of polyurethane-covered metal expandable stents for treatment of neoplastic distal biliary obstruction was analyzed...
  43. pmc Osteopontin is an initial mediator of inflammation and liver injury during obstructive cholestasis after bile duct ligation in mice
    Min Yang
    Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
    Toxicol Lett 224:186-95. 2014
    ..To test the hypothesis that OPN can modulate inflammatory liver injury during cholestasis, wild-type (WT) C57BL/6 and OPN knockout (OPN-KO) mice underwent bile duct ligation (BDL)...
  44. ncbi Idiopathic cholestasis as a paraneoplastic phenomenon in Hodgkin's lymphoma
    Stefan K Barta
    Department of Medicine, St Luke s Roosevelt Hospital Center, New York, NY, USA
    Clin Lymphoma Myeloma 7:77-82. 2006
    Paraneoplastic cholestasis is an uncommon presenting symptom in Hodgkin's lymphoma (HL). Two distinct entities causing this clinical picture have been described: idiopathic cholestasis and vanishing bile duct syndrome (VBDS)...
  45. ncbi Nuclear receptors in liver disease
    Martin Wagner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria
    Hepatology 53:1023-34. 2011
    ....
  46. ncbi Nuclear receptor regulation of the adaptive response of bile acid transporters in cholestasis
    Martin Wagner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
    Semin Liver Dis 30:160-77. 2010
    Although hereditary or acquired defects in hepatobiliary transporter systems cause or predispose to cholestasis, adaptive bile acid transporter changes can counteract cholestasis by reducing hepatocellular and systemic concentrations of ..
  47. pmc Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis
    Katryn Allen
    Department of Pharmacology, Toxicology, and Experimental Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
    Am J Pathol 178:175-86. 2011
    Inflammation contributes to liver injury during cholestasis. The mechanism by which cholestasis initiates an inflammatory response in the liver, however, is not known. Two hypotheses were investigated in the present studies...
  48. ncbi Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications
    Marcelo G Roma
    Institute of Experimental Physiology IFISE CONICET, Faculty of Biochemical and Pharmacautical Sciences, National University of Rosario, Suipacha 570, S2002LRL Rosario, Argentina
    Clin Sci (Lond) 121:523-44. 2011
    ..UDCA stabilizes plasma membranes against cytolysis by tensioactive bile acids accumulated in cholestasis. UDCA also halts apoptosis by preventing the formation of mitochondrial pores, membrane recruitment of death ..
  49. ncbi Oxidative stress and the pathogenesis of cholestasis
    Bryan L Copple
    Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
    Semin Liver Dis 30:195-204. 2010
    b>Cholestasis is a reduction in bile flow that occurs from a variety of causes in humans. This produces hepatocellular injury and fibrosis...
  50. ncbi Protective effect of Danning tablet on acute livery injury with cholestasis induced by α-naphthylisothiocyanate in rats
    Li Li Ding
    Department of Pharmacognosy, China Pharmaceutical University, Nanjing 201009, China
    J Ethnopharmacol 140:222-9. 2012
    ..Danning tablet, as a composite prescription of traditional Chinese medicine, has been used clinically to relieve liver and gallbladder diseases in China. However, the mechanisms involved are still unclear...
  51. ncbi Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver
    C J Soroka
    Liver Center and Department of Medicine, Yale University School of Medicine, New Haven, CT 06520-8019, USA
    Hepatology 33:783-91. 2001
    ..export pump multidrug resistance-associated protein 2 (Mrp2) is diminished in experimentally induced models of cholestasis. In this study we have examined the localization and expression of Mrp3, another member of the multidrug ..
  52. ncbi Orthotopic liver transplantation for cholestatic diseases
    W Patkowski
    Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Poland
    Hepatogastroenterology 57:605-10. 2010
    ..0% of cases. The aim of this study was to overview retrospective indications for operation and results of patients who underwent LTx for cholestatic diseases...
  53. pmc A mouse model of cholestasis-associated cholangiocarcinoma and transcription factors involved in progression
    Heping Yang
    Division of Gastroenterology and Liver Diseases, USC Research Center for Liver Diseases, Department of Medicine, Keck School of Medicine USC, Los Angeles, CA 90033, USA
    Gastroenterology 141:378-88, 388.e1-4. 2011
    b>Cholestasis contributes to hepatocellular injury and promotes liver carcinogenesis. We created a mouse model of chronic cholestasis to study its effects on progression of cholangiocarcinoma and the oncogenes involved.
  54. ncbi FXR and PXR: potential therapeutic targets in cholestasis
    Johan W Jonker
    Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
    J Steroid Biochem Mol Biol 130:147-58. 2012
    ..receptor (NR) family of ligand-modulated transcription factors are implicated in the adaptive response to cholestasis. NRs coordinately regulate bile acid and phospholipid transporter genes required for hepatobiliary transport, ..
  55. pmc Role of breast cancer resistance protein in the adaptive response to cholestasis
    Albert Mennone
    Department of Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 8019, USA
    Drug Metab Dispos 38:1673-8. 2010
    ..and food toxins, Bcrp can also transport bile acids and, therefore, may participate in the adaptive response to cholestasis. Bile duct ligation (BDL), an experimental model of obstructive cholestasis, was performed in male wild-type (..
  56. ncbi RIP3 inhibits inflammatory hepatocarcinogenesis but promotes cholestasis by controlling caspase-8- and JNK-dependent compensatory cell proliferation
    Mihael Vucur
    Department of Medicine III, University Hospital RWTH Aachen, D 52074 Aachen, Germany
    Cell Rep 4:776-90. 2013
    ..Moreover, RIP3 promotes the development of jaundice and cholestasis, because its activation suppresses compensatory proliferation of cholangiocytes and hepatic stem cells...
  57. ncbi Nuclear receptors as drug targets in cholestasis and drug-induced hepatotoxicity
    Gernot Zollner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Auenbruggerplatz 15, A 8036 Graz, Austria
    Pharmacol Ther 126:228-43. 2010
    ..or tested for the treatment of diabetes, dyslipidemia, fatty liver disease, cancer, drug hepatotoxicity and cholestasis. The hydrophilic bile acid ursodeoxycholic acid is currently the only available drug to treat cholestasis but ..
  58. pmc Effects of hepatocyte CD14 upregulation during cholestasis on endotoxin sensitivity
    Ming Huei Chou
    Institute of Basic Medical Sciences, National Chang Kung University, Tainan, Taiwan
    PLoS ONE 7:e34903. 2012
    b>Cholestasis is frequently related to endotoxemia and inflammatory response. Our previous investigation revealed a significant increase in plasma endotoxin and CD14 levels during biliary atresia...
  59. ncbi Thrombocytopenia exacerbates cholestasis-induced liver fibrosis in mice
    Takahiro Kodama
    Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    Gastroenterology 138:2487-98, 2498.e1-7. 2010
    ..It is not clear whether thrombocytopenia itself affects liver fibrosis...
  60. ncbi Comparison of axial force and cell width of self-expandable metallic stents: which type of stent is better suited for hilar biliary strictures?
    Tsuyoshi Mukai
    Department of Gastroenterology, Gifu Municipal Hospital, 7 1 Kashima cho, Gifu 500 8513, Japan
    J Hepatobiliary Pancreat Sci 18:646-52. 2011
    ..However, few reports have compared the performance of the various SEMSs. In addition to long-term patency, maneuverability during initial placement and feasibility of re-intervention for the stent occlusion are also very important...
  61. ncbi Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice
    Martin Wagner
    Department of Medicine, Karl Franzens University, Graz, Austria
    Gastroenterology 125:825-38. 2003
    b>Cholestasis induces changes in hepatic adenosine triphosphate-binding cassette (ABC) transporter expression...
  62. ncbi Drug-induced cholestasis
    Lakshumanan S Velayudham
    Storr Liver Unit, Westmead Millennium Institute, University of Sydney, NSW, Australia
    Expert Opin Drug Saf 2:287-304. 2003
    Drugs may cause several overlapping syndromes of cholestasis, the pathophysiological syndrome resulting from impaired bile flow...
  63. ncbi Silymarin as a new hepatoprotective agent in experimental cholestasis: new possibilities for an ancient medication
    Fernando A Crocenzi
    Instituto de Fisiología Experimental IFISE, Facultad de Ciencias Bioquímicas y Farmacéuticas CONICET U N R, S2002LRL, Rosario, Argentina
    Curr Med Chem 13:1055-74. 2006
    ..as a hepatoprotective drug, namely: its anticholestatic properties in experimental models of hepatocellular cholestasis with clinical correlate. For this purpose, this review will cover the following aspects: 1...
  64. ncbi Altered localization and activity of canalicular Mrp2 in estradiol-17beta-D-glucuronide-induced cholestasis
    Aldo D Mottino
    Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 0305, USA
    Hepatology 35:1409-19. 2002
    ..mixed plasma and intracellular membranes suggested partial internalization of Mrp2 during the acute phase of cholestasis at 20 minutes and during the period of recovery from cholestasis at 75 minutes, which returned to control ..
  65. ncbi Neonatal cholestasis
    Frederick J Suchy
    Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA
    Pediatr Rev 25:388-96. 2004
  66. ncbi Anterior pituitary hormone effects on hepatic functions in infants with congenital hypopituitarism
    Wikrom Karnsakul
    Department of Pediatrics, Section of Gastroenterology and Nutrition, West Virginia University School of Medicine, Morgantown, WV 26506 9214, USA
    Ann Hepatol 6:97-103. 2007
    Congenital hypopituitarism is an uncommon cause of neonatal cholestasis. Little is known about the effect of anterior pituitary hormone on hepatic functions.
  67. pmc Hepatoprotective role of PXR activation and MRP3 in cholic acid-induced cholestasis
    S Teng
    Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
    Br J Pharmacol 151:367-76. 2007
    ..As PXR alters the expression of numerous hepatic bile acid transporters, we sought to delineate their potential role in hepatoprotection...
  68. pmc Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis
    Yu Yamaura
    Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma machi, Kanazawa, Japan
    PLoS ONE 7:e30250. 2012
    ..study, we compared the changes of the plasma miRNA expressions by acute liver injury (hepatocellular injury or cholestasis) and chronic liver injury (steatosis, steatohepatitis and fibrosis) using rat models made by the administration ..
  69. ncbi Sepsis-induced cholestasis
    Nisha Chand
    Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298 0341, USA
    Hepatology 45:230-41. 2007
  70. pmc Impaired localisation and transport function of canalicular Bsep in taurolithocholate induced cholestasis in the rat
    F A Crocenzi
    Instituto de Fisiología Experimental IFISE, Facultad de Ciencias Bioquímicas y Farmacéuticas CONICET UNR, Rosario, Argentina
    Gut 52:1170-7. 2003
    Taurolithocholate induced cholestasis is a well established model of drug induced cholestasis with potential clinical relevance. This compound impairs bile salt secretion by an as yet unclear mechanism.
  71. ncbi Surgical management in biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury
    Ji Qi Yan
    Department of Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Road, Shanghai 200025, China
    World J Gastroenterol 13:6598-602. 2007
    ..To discuss the surgical method and skill of biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury...
  72. ncbi Fluconazole prophylaxis in extremely low birth weight infants: association with cholestasis
    Z H Aghai
    Department of Pediatrics, Division of Neonatology, Cooper University Hospital Robert Wood Johnson Medical School, One Cooper Plaza, Camden, NJ 08103, USA
    J Perinatol 26:550-5. 2006
    ..The use of fluconazole prophylaxis in this population has raised a benefit versus risk concern among clinicians...
  73. ncbi Update on the treatment of the pruritus of cholestasis
    Nora V Bergasa
    State University of New York at Downstate, USA
    Clin Liver Dis 12:219-34, x. 2008
    The pruritus of cholestasis is a difficult clinical problem to manage. It can be severe and interfere with sleep. Clinical behavioral studies have confirmed that the pruritus is mediated at least in part by endogenous opioids...
  74. ncbi Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats
    Fernando A Crocenzi
    Instituto de Fisiologia Experimental, Universidad Nacional de Rosario, Argentina
    Am J Physiol Gastrointest Liver Physiol 285:G449-59. 2003
    ..protein 2 (Mrp2) was previously suggested to be involved in estradiol-17beta-D-glucuronide (E217G)-induced cholestasis. Here we evaluated in the rat whether a similar phenomenon occurs with the bile salt export pump (Bsep) and the ..
  75. ncbi Nuclear receptors, bile-acid detoxification, and cholestasis
    Jiezhong Chen
    School of Pharmacy and Applied Science, Faculty of Science, Technology and Engineering, La Trobe University, Bendigo, VIC 3550, Australia
    Lancet 367:454-6. 2006
  76. ncbi High rates of mortality and morbidity occur in infants with parenteral nutrition-associated cholestasis
    Theresa C Willis
    United States Department of Agriculture Agricultural Research Service, Children s Nutrition Research Center and Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
    JPEN J Parenter Enteral Nutr 34:32-7. 2010
    Extremely few data are available about the natural history of parenteral nutrition (PN)-associated cholestasis. The authors evaluated a cohort of infants at a large center to determine the outcome of PN-associated cholestasis in infants ..
  77. pmc Disruption of the growth hormone--signal transducer and activator of transcription 5--insulinlike growth factor 1 axis severely aggravates liver fibrosis in a mouse model of cholestasis
    Leander Blaas
    Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria
    Hepatology 51:1319-26. 2010
    ..both in hepatocytes and cholangiocytes in the multidrug resistance gene 2 knockout (Mdr2(-/-)) mouse model of cholestasis. Double knockout mice develop an early and severe liver fibrosis phenotype, accompanied by perturbed expression ..
  78. ncbi Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: effects on primary bile acids in babies and mothers
    G Mazzella
    Dipartimento di Malattie dell Apparato Digerente, del Metabolismo and delle Malattie Infettive, Azienda Ospedaliera di Bologna, Universita di Bologna, Italy
    Hepatology 33:504-8. 2001
    Little is known about the effects on the fetus of ursodeoxycholic acid (UDCA) treatment for intrahepatic cholestasis of pregnancy (ICP). Twenty ICP patients were given UDCA at 1...
  79. ncbi Localization status of hepatocellular transporters in cholestasis
    Fernando A Crocenzi
    Instituto de Fisiología Experimental IFISE, CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, S2002LRL, Rosario, Argentina
    Front Biosci (Landmark Ed) 17:1201-18. 2012
    ..Exacerbated internalization of hepatocellular transporters occurs in several experimental models of cholestasis, and also in most human cholestatic liver diseases...
  80. ncbi Removable fully covered self-expandable metal stents in the treatment of common bile duct strictures due to chronic pancreatitis: a case series
    D L Cahen
    Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
    Endoscopy 40:697-700. 2008
    ..Nevertheless, before FCSEMS can become an acceptable treatment option for benign CBD strictures, innovative stent design modifications are necessary and removability must be ascertained...
  81. ncbi Exploration of Emodin to treat alpha-naphthylisothiocyanate-induced cholestatic hepatitis via anti-inflammatory pathway
    Yan Ding
    Department of Gastroenterology and Hepatology, Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, PR China
    Eur J Pharmacol 590:377-86. 2008
    ..The effects are mainly due to antagonizing pro-inflammatory cytokines and mediators, inhibiting oxidative damage, improving hepatic microcirculation, reducing impairment signals, and controlling neutrophil infiltration...
  82. ncbi Partially covered self-expandable metallic stents for benign biliary strictures due to chronic pancreatitis
    B Behm
    Digestive Health Center, University of Virginia Health System, Charlottesville, Virginia 22908 0708, USA
    Endoscopy 41:547-51. 2009
    ..We evaluated the temporary placement of partially covered self-expandable metallic stents (PCMS) in patients with BBS due to chronic pancreatitis...
  83. ncbi Sonographic diagnosis of biliary atresia in pediatric patients using the "triangular cord" sign versus gallbladder length and contraction
    Kimio Kanegawa
    Department of Radiology, Kobe Children s Hospital, 1 1 1 Takakuradai Suma ku, Kobe 654 0081, Japan
    AJR Am J Roentgenol 181:1387-90. 2003
    ..A retrospective review was performed to evaluate the importance of the "triangular cord" sign in comparison with gallbladder length and contraction for the diagnosis of biliary atresia in pediatric patients...
  84. ncbi Itch: scratching more than the surface
    R Twycross
    Sir Michael Sobell House, Churchill Hospital, Oxford, OX3 7LJ, UK
    QJM 96:7-26. 2003
    ..g. dermatitis), neuropathic (e.g. multiple sclerosis), neurogenic (e.g. cholestasis), mixed (e.g. uraemia) or psychogenic...
  85. ncbi New molecular insights into the mechanisms of cholestasis
    Martin Wagner
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Laboratory of Experimental and Molecular Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
    J Hepatol 51:565-80. 2009
    ..has enhanced our understanding of the molecular mechanisms of normal bile secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause ..
  86. ncbi Folding defects in P-type ATP 8B1 associated with hereditary cholestasis are ameliorated by 4-phenylbutyrate
    Lieke M van der Velden
    Department of Metabolic and Endocrine Diseases, University Medical Center UMC Utrecht, The Netherlands
    Hepatology 51:286-96. 2010
    ..is a severe and clinically highly variable hereditary disorder that is primarily characterized by intrahepatic cholestasis. It presents either as a progressive (progressive familial intrahepatic cholestasis type 1 [PFIC1]) or ..
  87. ncbi Cellular regulation of hepatic bile acid transport in health and cholestasis
    M Sawkat Anwer
    Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, 200 Westboro Road, N Grafton, MA 01536, USA
    Hepatology 39:581-90. 2004
  88. ncbi Drug insight: Mechanisms and sites of action of ursodeoxycholic acid in cholestasis
    Ulrich Beuers
    Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany
    Nat Clin Pract Gastroenterol Hepatol 3:318-28. 2006
    ..synthesis, targeting and apical membrane insertion of key transporters, seems to be relevant in more advanced cholestasis. In intrahepatic cholestasis of pregnancy, stimulation of impaired hepatocellular secretion could be crucial ..
  89. ncbi Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver
    M G Donner
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Hepatology 34:351-9. 2001
    b>Cholestasis induces down-regulation of multidrug resistance protein 2 (Mrp2, symbol Abcc2), which is localized to the canalicular membrane...
  90. pmc Inhibition of Na+-taurocholate Co-transporting polypeptide-mediated bile acid transport by cholestatic sulfated progesterone metabolites
    Shadi Abu-Hayyeh
    Institute for Reproductive and Developmental Biology, Imperial College London, London W12 0NN, United Kingdom
    J Biol Chem 285:16504-12. 2010
    ..progesterone metabolite (P4-S) levels are raised in normal pregnancy and elevated further in intrahepatic cholestasis of pregnancy (ICP), a bile acid-liver disorder of pregnancy...
  91. ncbi A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction
    Jennifer J Telford
    St Paul s Hospital, Vancouver, British Columbia, Canada
    Gastrointest Endosc 72:907-14. 2010
    ..The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency...
  92. pmc Benefit of farnesoid X receptor inhibition in obstructive cholestasis
    Catherine Stedman
    Department of Clinical Pharmacology, Molecular Pharmacology Laboratory, Westmead Millennium Institute, Westmead Hospital, University of Sydney, Sydney NSW 2145, Australia
    Proc Natl Acad Sci U S A 103:11323-8. 2006
    ..FXR knockout (KO) mice were found to be protected from obstructive cholestasis. Concurrent deletion of FXR also could ameliorate an increase in liver injury that is seen usually in pregnane ..
  93. ncbi Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited
    Gustav Paumgartner
    Department of Medicine II, Klinikum Grosshadern, University of Munich, Munich, Germany
    Hepatology 36:525-31. 2002
    ..Anticholestatic effects of UDCA have also been reported in intrahepatic cholestasis of pregnancy, liver disease of cystic fibrosis, progressive familial intrahepatic cholestasis, and chronic ..
  94. ncbi Mrp4-/- mice have an impaired cytoprotective response in obstructive cholestasis
    Albert Mennone
    Liver Center and Department of Medicine, Yale University School of Medicine, New Haven, CT, USA
    Hepatology 43:1013-21. 2006
    ..In conclusion, hepatic Mrp4 plays a unique and essential protective role in the adaptive response to obstructive cholestatic liver injury...
  95. ncbi Pharmacological actions of curcumin in liver diseases or damage
    Yadira Rivera-Espinoza
    Departamento de Graduados e Investigacion en Alimentos, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Carpio y Plan de Ayala, Mexico City, Mexico
    Liver Int 29:1457-66. 2009
    ..Curcumin attenuates liver injury induced by ethanol, thioacetamide, iron overdose, cholestasis and acute, subchronic and chronic carbon tetrachloride (CCl(4)) intoxication; moreover, it reverses CCl(4) ..
  96. ncbi Temporary placement of covered self-expandable metal stents in benign biliary strictures: a new paradigm? (with video)
    Michel Kahaleh
    Digestive Health Center, University of Virginia Health System, Charlottesville, Virginia 22908 0708, USA
    Gastrointest Endosc 67:446-54. 2008
    ..Benign biliary strictures (BBS) are usually managed with plastic stents, whereas placement of uncovered metallic stents has been associated with failure related to mucosal hyperplasia...
  97. ncbi MDR3 (ABCB4) defects: a paradigm for the genetics of adult cholestatic syndromes
    Michael Trauner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria
    Semin Liver Dis 27:77-98. 2007
    ..bile secretion, hereditary and acquired ABC transporter defects play a central role in the pathogenesis of cholestasis. Defects of the phospholipid export pump MDR3 ( ABCC4) result in impaired biliary excretion of ..
  98. pmc Nuclear receptors as therapeutic targets in cholestatic liver diseases
    Gernot Zollner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
    Br J Pharmacol 156:7-27. 2009
    b>Cholestasis results in intrahepatic accumulation of cytotoxic bile acids, which cause liver damage ultimately leading to biliary fibrosis and cirrhosis...
  99. ncbi Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases
    G Zollner
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Karl-Franzens University Graz, Austria
    Hepatology 33:633-46. 2001
    ..could explain impaired hepatic uptake and excretion of bile salts and other biliary constituents resulting in cholestasis and jaundice...
  100. ncbi Melatonin prevents oxidative stress and hepatocyte cell death induced by experimental cholestasis
    Francisco J Padillo
    Unit of Hepatobiliary Surgery, Department of General Surgery, Reina Sofia University Hospital, Avda Menendez Pidal s n 14 004, Cordoba, Spain
    Free Radic Res 38:697-704. 2004
    ..MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status ..
  101. ncbi Fxr(-/-) mice adapt to biliary obstruction by enhanced phase I detoxification and renal elimination of bile acids
    Hanns Ulrich Marschall
    Karolinska Institutet, Department of Medicine at Karolinska University Hospital Huddinge, S 14186 Stockholm, Sweden
    J Lipid Res 47:582-92. 2006
    ..In conclusion, Fxr(-/-) mice detoxify accumulating bile acids in the liver by enhanced hydroxylation reactions probably catalyzed by Cyp3a11. The metabolites formed were excreted into urine, most likely with the participation of Mrp4...

Research Grants69

  1. Mice Humanized with Hepatocytes and iPS Cells from Patients with Metabolic Diseas
    Stephen C Strom; Fiscal Year: 2010
    ..For example mutations in the bile salt export pump (BSEP) results in severe cholestasis and fibrosis in human patients requiring whole organ transplants, yet the knockout mouse is nearly without a ..
  2. Histamine modulation of biliary proliferation and damage
    Heather L Francis; Fiscal Year: 2013
    ..HRs);and (ii) H1HR and H2HR stimulate cholangiocyte growth, whereas H3HR or H4HR inhibit biliary growth during cholestasis. In addition to cholangiocytes, histamine is synthesized mainly from mast cells in response to many pathologies ..
  3. Liver disease in CF: CFTR controls innate immunity in biliary epithelium
    Mario Strazzabosco; Fiscal Year: 2013
    ..spontaneous development of CFLD is extremely rare, suggesting that genetic and/or acquired factors other than cholestasis are at play...
  4. Mechanisms of Neutrophil-induced Liver Toxicity
    HARTMUT W JAESCHKE; Fiscal Year: 2012
    ..injury (transplantation, tumor resections), alcoholic hepatitis, steatohepatitis and obstructive cholestasis. However, these leukocytes also fulfill a vital host defense function against invading microorganisms...
  5. Excessive Copper Levels Disrupt Hepatic Nuclear Receptor Function
    Clavia Ruth Wooton-Kee; Fiscal Year: 2011
    ..in the Cu-transporting P-type ATPase, ATP7b, and is associated with a variety of symptoms including steatosis, cholestasis, cirrhosis, and liver failure, as well as neurological dysfunction...
  6. Biliary Atresia, Cholestatic Liver Diseases, and Cystic Fibrosis: Indiana Univers
    Jean Pappas Molleston; Fiscal Year: 2013
    ..Biliary atresia accounts for more than half of pediatric liver transplants. Genetic causes of neonatal cholestasis include Alagille's syndrome, alpha-1-antitrypsin deficiency, Progressive Familial Intrahepatic Cholestasis ..
  7. DYSREGULATION OF GSH SYNTHESIS DURING LIVER INJURY AND FIBROSIS
    SHELLY CHI LOO LU; Fiscal Year: 2013
    ..SAMe) prevented the fall in GCL subunits mRNA levels in hepatocytes (UDCA and SAMe) during cholestasis, and in macrophages (SAMe) during LPS treatment...
  8. Colorado Center for Childhood Liver Disease Research and Education
    Ronald J Sokol; Fiscal Year: 2013
    ..In cholestasis, impairment of bile flow leads to the accumulation of hepatotoxic bile acids, cholesterol and other compounds ..
  9. The Pittsburgh Cholestatic Liver Disease Consortium
    Benjamin L Shneider; Fiscal Year: 2013
    ..defects, biliary atresia, cystic fibrosis, mitochondrial hepatopathies and progressive familial intrahepatic cholestasis, lead to significant morbidity and mortality in childhood and frequently necessitate liver transplantation...
  10. MOLECULAR REGULATION OF ILEAL/RENAL BILE ACID TRANSPORT
    Benjamin L Shneider; Fiscal Year: 2012
    ..diarrhea, while partial inhibition of ASBT-mediated transport can be used to treat hypercholesterolemia and cholestasis. NIH supported investigations in my laboratory have advanced our understanding of the molecular regulation of ..
  11. Epigenetic regulation of liver transporters
    Frederick J Suchy; Fiscal Year: 2013
    ..receptor for bile acids, regulate the expression of liver transport proteins in the normal liver and during cholestasis. We propose that epigenetic modification of chromatin into repressive or permissive configurations provides a ..
  12. Crosstalk between estrogen and bile acid signaling pathway
    Ruitang Deng; Fiscal Year: 2013
    ..Among diseases resulted from imbalance of bile acid levels, intrahepatic cholestasis of pregnancy (ICP) and gallstone disease are both associated with sex hormone estrogen...
  13. The Role of Genetics in Innate Immunity Following Cholestasis
    Samuel M Alaish; Fiscal Year: 2011
    ..A description of the research project follows: Defined as little or no bile flow, cholestasis is a common condition associated with significant and sometimes devastating complications in both children and ..
  14. Regulation of Hepatic Metabolic Function by Parenteral Nutrition
    Douglas G Burrin; Fiscal Year: 2013
    ..studies in premature piglets show that TPN enriched with phytosterols and n-6 fatty acids (FA) induces hepatic cholestasis, steatosis and inflammation compared to enteral nutrition...
  15. Structure/Function of Steroid Transforming AKR's
    Trevor M Penning; Fiscal Year: 2011
    ..have been associated with 5[unreadable]-reductase deficiency, which results in fatal neonatal hepatitis and cholestasis. Whether these mutations are the molecular basis of this disease has not been established...
  16. Control of cAMP Mediated Glucagon Response by Bile Acids
    Norman H Lee; Fiscal Year: 2011
    ..glucagon responsiveness, which is one of the events associated to the progression of liver disease during cholestasis. The aims of the proposed study are: 1) Identification in vitro by a proteomic approach of the PKC residues ..
  17. Interplay between metabolism and FXR activation in scoparone signaling
    Bingfang Yan; Fiscal Year: 2013
    ..The central hypothesis of this project is that scoparone metabolites confer potent hepatic protection against cholestasis by efficaciously modulating FXR phosphorylation...
  18. Functions of MRP2 and MRP3 in Drug Disposition
    James M Gallo; Fiscal Year: 2011
    ..gut enterocytes, and is induced at basolateral surfaces of hepatocytes during conditions of liver dysfunction (cholestasis) in which the canalicular route of drug detoxification is blocked...
  19. Regulation of Sulfotransferases by LXR and its Implication in Pathophysiology
    Wen Xie; Fiscal Year: 2011
    ..of bile acid- and estrogen-metabolizing SULTs will lead to the alleviation of bile acid hepatotoxicity and cholestasis as well as down-regulation of estrogen activity in vivo...
  20. Drs2p Function in Clathrin-coated Vesicle Budding
    Todd R Graham; Fiscal Year: 2013
    ..Moreover, deficiency of a human P4-ATPase (Atp8b1) causes familial intrahepatic cholestasis, a disease where loss of PS asymmetry in the bile canalicular membrane leads to damage of this membrane by ..
  21. Establichment of CHLA's ChilDREN Clinical Center
    KASPER SAONUN WANG; Fiscal Year: 2013
    ..Consortium, along with Alagille syndrome (AGS), alpha-1-antitrypsin deficiency, progressive intrahepatic cholestasis, bile acid synthesis defects, mitochondrial hepatopathies, and cystic fibrosis liver disease, studied under the ..
  22. Center for the Study of Pediatric Cholestasis
    Ronen Arnon; Fiscal Year: 2013
    ..clinical features, the correlation of genotype with phenotype, and prognosis of inherited forms of intrahepatic cholestasis including Alagille syndrome, alpha-1-antitrypsin deficiency, progressive familial intrahepatic cholestasis (..
  23. Mechanisms of xenobiotic-induced biliary inflammation and fibrosis
    James P Luyendyk; Fiscal Year: 2013
    ..The broad, long term goal of this proposal is to elucidate the mechanism whereby xenobiotic-induced cholestasis causes inflammation and fibrosis...
  24. Rare Liver Disease Network
    Ronald J Sokol; Fiscal Year: 2010
    ..The RLDN will focus on investigations of five genetic causes of intrahepatic cholestasis. These disorders have serious if not fatal consequences (without liver transplantation) and severely affect the ..
  25. Gut bile acids, Fxr, &Fgf15 in total parenteral nutrition-associated cholestasis
    Grace L Guo; Fiscal Year: 2013
    ..Long-term TPN is associated with a severe complication, TPN-associated cholestasis (TPN-AC). The mechanism underlying the cause of TPN-AC is poorly understood...
  26. Childhood Liver Disease Research and Education Network (CHiLDREN) - UCSF (CC)
    Philip Rosenthal; Fiscal Year: 2013
    ..5) Phase l/ll study of new agents to treat cholestasis in children. 6) Study of modifier genes in Alagille Syndrome and Alpha-1-antrypsin disease...
  27. ALIMENTARY TRACT LIPIDS IN HEALTH AND DISEASE
    MARTIN CONRAD CAREY; Fiscal Year: 2013
    ..biologic techniques to advance fundamental understanding of bile and its two major dysfunctions, namely cholestasis and gallstones of both pigment and cholesterol types, i) The first aim will determine whether enterohepatic ..
  28. Dysregulated Hypothalamic-pituitary-adrenal Axis During Biliary Hyperplasia
    Sharon Demorrow; Fiscal Year: 2013
    ..liver disease and that this may contribute to the cholangiocyte outgrowth seen in the early stages of cholestasis. The overall objective of this proposal is to determine the consequences of cholestatic liver disease on the ..
  29. Molecular mechanisms of Bile Duct Proliferation in Mice with Glycosylation Defect
    MATTHEW JOSEPH RYAN; Fiscal Year: 2012
    ..in either the JAG1 or NOTCH2 genes and characterized by a paucity of bile ducts in the liver with resultant cholestasis. Despite the knowledge of the genes responsible for ALGS, there exists a wide phenotypic variability even ..
  30. Regulation of Bile Duct Growth in Bile Duct Ligated Rats
    SHANNON STROUD GLASER; Fiscal Year: 2013
    ..expressed in the liver mainly by cholangiocytes) participates in the homeostasis of the biliary mass during cholestasis and liver damage...
  31. JAUNDICE NEXT: A diagnostic tool for cholestatic liver disease.
    Frank Zemlan; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Cholestasis (or pathologic jaundice) is the most common sign of liver disease in children and often results from mutations in genes that play a critical role in bile formation and transport...
  32. Ca2+ Waves in Hepatocytes: Mechanisms and Effects
    Michael H Nathanson; Fiscal Year: 2013
    ..InsP3Rs will impair regulated delivery of these transporters to the canalicular membrane, and thus lead to cholestasis. This hypothesis will be tested through three specific aims: (1) The role of impaired Ca2+ signaling in the ..
  33. Isolation, Identification and Characterization of a Toxin Causing Biliary Atresia
    Rebecca G Wells; Fiscal Year: 2013
    ..by applicant): Biliary atresia (BA) is a fibro inflammatory disorder that is the leading cause of neonatal cholestasis and the most common indication for liver transplant in the pediatric population...
  34. ABC-transporter binding proteins and trafficking
    Daniel F Ortiz; Fiscal Year: 2010
    ..Mutations that cause BSEP retention in the endoplasmic reticulum produce Progressive Familial Intrahepatic Cholestasis type II...
  35. Control of Sterol and Lipoprotein Homeostasis by miRNA
    Angel Baldán; Fiscal Year: 2013
    ..HDL lipidation and reverse cholesterol transport, and ATP8B1, a phospholipid flippase linked to intrahepatic cholestasis. The broad goal of this proposal is to determine the role of miR-33 on cholesterol, bile and lipoprotein ..
  36. Mechanosensitive Signaling and Cholangiocyte Secretion
    Andrew P Feranchak; Fiscal Year: 2013
    ..Liver diseases associated with impaired bile flow (cholestasis) account for significant morbidity and mortality in both children and adults...
  37. A genetic model of cholestasis induced neonatal
    John D Schuetz; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Recent epidemiological data indicate intrahepatic cholestasis of pregnancy (ICP) has an incidence of between 1.5-4% and is related to serum bile acid concentrations...
  38. Role of Early Growth Response Factor-1 in Cholestatic Liver Injury
    Bryan L Copple; Fiscal Year: 2011
    The overall goal of this proposal is to elucidate the mechanism by which cholestasis triggers production of proinflammatory mediators in the liver...
  39. Regulation of cholangiocytes by InsP3 receptor isoforms
    Michael H Nathanson; Fiscal Year: 2012
    ..Abnormal cholangiocyte function results in cholestasis, which is a cardinal manifestation of liver disease...
  40. The Regulation of Human Hydroxysteroid Sulfotransferase by Nuclear Receptor ROR
    Wen Xie; Fiscal Year: 2012
    ..SULT2A1-mediated bile acid sulfation and detoxification play an important role in the prevention and relief of cholestasis. Results from this study may help to understand the role of RORs in the interindividual variation of SULT2A1 ..
  41. Midwest Children's Consortium
    Yumirle P Turmelle; Fiscal Year: 2013
    ..practices and laboratory utilization in an attempt to accelerate identification and referral of infants with cholestasis, focussing on the critical events surrounding presentation, with the goal of defining, then reducing, the ..
  42. Role of Protein Kinase C in Isoforms in Bile formation and Cholestasis
    MOHAMMED SAWKAT ANWER; Fiscal Year: 2013
    ..Our present understanding of the pathogenesis of cholestasis is based on studies to define the physiological regulation of transporters involved in bile formation and their ..
  43. Autocrine/Paracrine Regulation of Intrahepatic Bile Duct Growth
    GIANFRANCO D ALPINI; Fiscal Year: 2013
    ..secretin receptor gene ablates the proliferative and apoptotic responses of small and large cholangiocytes to cholestasis and liver injury;and (iii) To define the in vitro intracellular mechanisms regulating secretin and secretin ..
  44. Molecular Mechanisms of Intrahepatic Cholestasis
    Benjamin L Shneider; Fiscal Year: 2013
    ..the applicant): FIC1 disease includes a spectrum of liver problems ranging from "benign" recurrent intrahepatic cholestasis (BRIC) to severe, unremitting and histologically progressive cholestasis (Byler Disease)...
  45. Organelle Dysfunction and Apoptosis in Liver Epithelia
    Gregory J Gores; Fiscal Year: 2013
    ..killing via this pathway in vivo, whereas hepatocytes in vivo only become sensitive to TRAIL toxicity during cholestasis. Based upon this preliminary data, we propose the novel CENTRAL HYPOTHESIS that TRAIL induces liver cell death ..
  46. FXR, nuclear receptors, and transcriptional regulation of liver homeostasis
    Grace L Guo; Fiscal Year: 2011
    ..Clearly, FXR is important for liver function because FXR deficiency in mice causes cholestasis, dyslipidemia, gallstone, hepatocellular carcinoma and diabetes...
  47. Investigation of the mechanism by which NPC1 dysfunction leads to liver disease
    Laura Liscum; Fiscal Year: 2012
    ..NPC patients suffer from cholestasis, prolonged jaundice, and hepatosplenomegaly...
  48. Cholestasis and the Unfolded Protein Response
    Richard M Green; Fiscal Year: 2013
    ..The central hypothesis of this proposal is that XBP1s is protective to the live during cholestasis~ and attenuated hepatic expression of XBP1s results in diminished expression of liver bile salt transporters ..
  49. The Genetic Basis of Pediatric Cholestasis
    RICHARD JOHN THOMPSON; Fiscal Year: 2012
    ..group of patients was identified some years ago, and their disorder termed progressive familial intrahepatic cholestasis (PFIC)...
  50. Emory Clinical Center: Childhood Liver Disease Research and Education Network
    Rene Romero; Fiscal Year: 2011
    ..Genetic cholestatic liver diseases, such as alagille syndrome, progressive familial intrahepatic cholestasis, mitochondrial hepatopathies and cystic fibrosis associated liver disease are poorly understood and difficult ..
  51. Tissue specific mechanism of FXR in suppressing bile-acid synthesis
    Grace L Guo; Fiscal Year: 2011
    ..FXR dysfunction contributes to the development of cholestasis, gallstones, fatty-liver disease, and liver tumor...
  52. Kinetic and structural analysis of human steroid 5beta-reductase (AKR1D1)
    Mo Chen; Fiscal Year: 2012
    ..Deficiency in AKR1D1 induces neonatal hepatitis and cholestasis that can be fatal. The exact role of AKR1D1 in sexual and reproductive functions is still under investigation...
  53. MECHANISMS OF LIVER CELL INJURY
    Gregory Gores; Fiscal Year: 2009
    ..injury in human disease, our program is working on the cellular mechanisms causing hepatocyte injury during cholestasis. Specifically, our long-term goal is to understand the cellular mechanisms by which bile salts, which ..
  54. THE GENETIC BASIS OF CHOLESTASIS
    Laura N Bull; Fiscal Year: 2010
    Abstract Liver disease is a cause of substantial morbidity and mortality in the U.S., and cholestasis (impairment of bile flow) is a common and devastating manifestation of liver disease...
  55. Molecular requirements for proliferation of fetal and adult liver progenitors
    Stacey S Huppert; Fiscal Year: 2012
    ..A distinguishing characteristic of this syndrome is cholestasis brought on by paucity of bile ducts...
  56. MECHANISMS OF BILE SECRETION AND CHOLESTASIS
    JAMES LORENZEN BOYER; Fiscal Year: 2013
    ..major function of the liver which is frequently impaired in diseases of the liver resulting in the syndrome of cholestasis. The long term objectives of this grant, funded continuously by NIDDK since 1973, have been to characterize the ..
  57. Clinical Center: Childhood Liver Disease Research and Education Network (ChiLDREN
    PETER FRANK WHITINGTON; Fiscal Year: 2013
    ..A major objective of this application is to participate in ChiLDREN as an expert in genetically determined cholestasis (in particular progressive familial intrahepatic cholestasis) and in clinical aspects of infantile cholestatic ..
  58. Genetic Modifiers of Liver Disease Severity in Alagille Syndrome
    Nancy Bettina Spinner; Fiscal Year: 2013
    ..The liver disease in AGS is characterized pathologically by intrahepatic bile duct paucity, with resulting cholestasis, and ranges from very mild (sub-clinical with only biochemical abnormalities of liver enzymes) to severe, in ..
  59. PROTEIN COMPARTMENTATION
    WILLIAM TOBEY WICKNER; Fiscal Year: 2013
    ..complex, discovered and studied in this work, underlies studies of human arthrogryposis, renal dysfunction, and cholestasis syndromes, caused by mutations in the human VPS33 gene...
  60. The Childhood Liver Disease Research and Education Network (ChilDREN)
    SAUL JOSEPH KARPEN; Fiscal Year: 2013
    ..Since there are currently no effective medical therapies for cholestasis, proper exploration of the safety and efficacy of this investigational agent would perfectly fit within the ..
  61. GROWTH REGULATION OF THE INTRAHEPATIC BILIARY TREE
    GIANFRANCO D ALPINI; Fiscal Year: 2010
    ..mechanisms regulating the differential proliferative responses of small and large Cholangiocytes to cholestasis and liver injury/toxins will play an important role in the development of therapeutic strategies for the ..
  62. PHYSICAL CHEMISTRY OF BILIRUBIN & ITS CONJUGATES
    WILLIAM SPIVAK; Fiscal Year: 1990
    ..bile pigment found in animal models of gallstone formation and premature neonates who are particularly prone to cholestasis, undergoes non-enzymatic alkaline aqueous hydrolysis to insoluble UCB in model bile systems (and in guinea pig ..
  63. Advancing our Understanding of Rare Pediatric Liver Diseases
    KATHLEEN MARY LOOMES; Fiscal Year: 2013
    ..Alagille syndrome (AGS), alpha-one antitrypsin deficiency, progressive familial intrahepatic cholestasis, bile acid synthetic disorders, cystic fibrosis liver disease and neonatal hepatitis...
  64. MOLECULAR PHYSIOLOGY OF BILIARY LIPID SECRETION
    David Cohen; Fiscal Year: 2000
    ..cholesterol elimination from the body, and abnormalities in bile secretion may result in gallstone formation, cholestasis, biliary cirrhosis, hypercholesterolemia and fat malabsorption...
  65. Role of the Renin-Angiotensin System in the Regulation of Biliary Proliferation
    SHANNON STROUD GLASER; Fiscal Year: 2010
    ..The elucidation of the factors regulating the proliferative responses of cholangiocytes to cholestasis is critical for the development of therapeutic strategies for the treatment of cholestatic liver diseases...
  66. EFFECT OF VITAMIN E ON HEPATOCYTE STRUCTURE AND FUNCTION
    Ronald Sokol; Fiscal Year: 1991
    ..clearance of circulating bile acids may be impaired by the vitamin E deficiency state in children with chronic cholestasis and in normal rats, presumably due to alterations in hepatocyte membrane properties essential for transport and ..
  67. HEPATIC DRUG ELIMINATION IN PREGNANCY
    Mary Vore; Fiscal Year: 2010
    ..TUDC), a bile acid used for the treatment of cholestatic liver disease, including intrahepatic cholestasis of pregnancy (ICP), 2) estradiol-17[3- D-glucuronide (E217G) causes increased permeability of the ..
  68. HEPATIC DRUG ELIMINATION IN PREGNANCY
    Mary Vore; Fiscal Year: 2007
    ..TUDC), a bile acid used for the treatment of cholestatic liver disease, including intrahepatic cholestasis of pregnancy (ICP), 2) estradiol-17B-D-glucuronide (E217G) causes increased permeability of the hepatocellular ..
  69. Role of Nrf2 during cholestsis and gallstone formation
    ANGELA SLITT; Fiscal Year: 2009
    ..Gallstones can cause extrahepatic cholestasis by occluding the common bile duct...