Advertisement

Primary Sclerosing Cholangitis

  • Marina G. Silveira
  • Keith D. Lindor
Chapter
Part of the Molecular Pathology Library book series (MPLB, volume 5)

Abstract

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by fibrosing inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts [1], leading to bile stasis, hepatic fibrosis and ultimately to cirrhosis, end-stage liver disease, and need for liver transplantation (LT). The majority of cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC [2]. The etiology of PSC is undefined, apart from an increasing body of evidence that points to an immunologic disturbance as a component of the disease. However, PSC lacks the features of a typical autoimmune disease and responds poorly, if at all, to typical immunosuppressive therapies [3]. No effective medical therapy for halting disease progression has been identified. A median duration of 12–18 years from the time of diagnosis before patients develop end-stage liver disease has been described. Among eligible patients, LT is currently the only life-extending therapy for patients with end-stage PSC, although the disease can recur in the allografted liver and be a cause of morbidity post-transplant [4].

Keywords

Inflammatory Bowel Disease Liver Transplantation Human Leukocyte Antigen Cystic Fibrosis Transmembrane Conductance Regulator Primary Sclerosing Cholangitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med. 1995;332(14):924–33.PubMedGoogle Scholar
  2. 2.
    Talwalkar JA, Lindor KD. Primary sclerosing cholangitis. Inflamm Bowel Dis. 2005;11(1):62–72.PubMedGoogle Scholar
  3. 3.
    LaRusso NF, Shneider BL, Black D, et al. Primary sclerosing cholangitis: summary of a workshop. Hepatology. 2006;44(3):746–64.PubMedGoogle Scholar
  4. 4.
    Gautam M, Cheruvattath R, Balan V. Recurrence of autoimmune liver disease after liver transplantation: a systematic review. Liver Transpl. 2006;12(12):1813–24.PubMedGoogle Scholar
  5. 5.
    Bambha K, Kim WR, Talwalkar J, et al. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology. 2003;125(5):1364–9.PubMedGoogle Scholar
  6. 6.
    Boberg KM, Aadland E, Jahnsen J, Raknerud N, Stiris M, Bell H. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol. 1998;33(1):99–103.PubMedGoogle Scholar
  7. 7.
    Kingham JG, Kochar N, Gravenor MB. Incidence, clinical patterns, and outcomes of primary sclerosing cholangitis in South Wales, United Kingdom. Gastroenterology. 2004;126(7):1929–30.PubMedGoogle Scholar
  8. 8.
    Schrumpf E, Boberg KM. Epidemiology of primary sclerosing cholangitis. Best Pract Res Clin Gastroenterol. 2001;15(4):553–62.PubMedGoogle Scholar
  9. 9.
    Farrant JM, Hayllar KM, Wilkinson ML, et al. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology. 1991;100(6):1710–7.PubMedGoogle Scholar
  10. 10.
    Chapman RW, Arborgh BA, Rhodes JM, et al. Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology. Gut. 1980;21(10):870–7.PubMedGoogle Scholar
  11. 11.
    Wiesner RH, Grambsch PM, Dickson ER, et al. Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis. Hepatology. 1989;10(4):430–6.PubMedGoogle Scholar
  12. 12.
    Wiesner RH, LaRusso NF. Clinicopathologic features of the syndrome of primary sclerosing cholangitis. Gastroenterology. 1980;79(2):200–6.PubMedGoogle Scholar
  13. 13.
    Broome U, Olsson R, Loof L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996;38(4):610–5.PubMedGoogle Scholar
  14. 14.
    Okolicsanyi L, Fabris L, Viaggi S, Carulli N, Podda M, Ricci G. Primary sclerosing cholangitis: clinical presentation, natural history and prognostic variables: an Italian multicentre study. The Italian PSC Study Group. Eur J Gastroenterol Hepatol. 1996;8(7):685–91.PubMedGoogle Scholar
  15. 15.
    Broome U, Bergquist A. Primary sclerosing cholangitis, inflammatory bowel disease, and colon cancer. Semin Liver Dis. 2006;26(1):31–41.PubMedGoogle Scholar
  16. 16.
    Rasmussen HH, Fallingborg JF, Mortensen PB, Vyberg M, Tage-Jensen U, Rasmussen SN. Hepatobiliary dysfunction and primary sclerosing cholangitis in patients with Crohn’s disease. Scand J Gastroenterol. 1997;32(6):604–10.PubMedGoogle Scholar
  17. 17.
    Fausa O, Schrumpf E, Elgjo K. Relationship of inflammatory bowel disease and primary sclerosing cholangitis. Semin Liver Dis. 1991;11(1):31–9.PubMedGoogle Scholar
  18. 18.
    Aron JH, Bowlus CL. The immunobiology of primary sclerosing cholangitis. Semin Immunopathol. 2009;31(3):383–97.Google Scholar
  19. 19.
    O’Mahony CA, Vierling JM. Etiopathogenesis of primary sclerosing cholangitis. Semin Liver Dis. 2006;26(1):3–21.PubMedGoogle Scholar
  20. 20.
    Eksteen B, Grant AJ, Miles A, et al. Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis. J Exp Med. 2004;200(11):1511–7.PubMedGoogle Scholar
  21. 21.
    Grant AJ, Lalor PF, Hubscher SG, Briskin M, Adams DH. MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease). Hepatology. 2001;33(5):1065–72.PubMedGoogle Scholar
  22. 22.
    Adams DH, Eksteen B. Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease. Nat Rev Immunol. 2006;6(3):244–51.PubMedGoogle Scholar
  23. 23.
    Harada K, Kono N, Tsuneyama K, Nakanuma Y. Cell-kinetic study of proliferating bile ductules in various hepatobiliary diseases. Liver. 1998;18(4):277–84.PubMedGoogle Scholar
  24. 24.
    Floreani A, Guido M, Bortolami M, et al. Relationship between apoptosis, tumour necrosis factor, and cell proliferation in chronic cholestasis. Dig Liver Dis. 2001;33(7):570–5.PubMedGoogle Scholar
  25. 25.
    Tinmouth J, Lee M, Wanless IR, Tsui FW, Inman R, Heathcote EJ. Apoptosis of biliary epithelial cells in primary biliary cirrhosis and primary sclerosing cholangitis. Liver. 2002;22(3):228–34.PubMedGoogle Scholar
  26. 26.
    Wu CT, Eiserich JP, Ansari AA, et al. Myeloperoxidase-positive inflammatory cells participate in bile duct damage in primary biliary cirrhosis through nitric oxide-mediated reactions. Hepatology. 2003;38(4):1018–25.PubMedGoogle Scholar
  27. 27.
    Bergquist A, Lindberg G, Saarinen S, Broome U. Increased prevalence of primary sclerosing cholangitis among first-degree relatives. J Hepatol. 2005;42(2):252–6.PubMedGoogle Scholar
  28. 28.
    Cassinotti A, Birindelli S, Clerici M, et al. HLA and autoimmune digestive disease: a clinically oriented review for gastroenterologists. Am J Gastroenterol. 2009;104(1):195–217. quiz 194, 218.PubMedGoogle Scholar
  29. 29.
    Schrumpf E, Fausa O, Forre O, Dobloug JH, Ritland S, Thorsby E. HLA antigens and immunoregulatory T cells in ulcerative colitis associated with hepatobiliary disease. Scand J Gastroenterol. 1982;17(2):187–91.PubMedGoogle Scholar
  30. 30.
    Henckaerts L, Jaspers M, Van Steenbergen W, et al. Cystic fibrosis transmembrane conductance regulator gene polymorphisms in patients with primary sclerosing cholangitis. J Hepatol. 2009;50(1):150–7.PubMedGoogle Scholar
  31. 31.
    Farrant JM, Doherty DG, Donaldson PT, et al. Amino acid substitutions at position 38 of the DR beta polypeptide confer susceptibility to and protection from primary sclerosing cholangitis. Hepatology. 1992;16(2):390–5.PubMedGoogle Scholar
  32. 32.
    Mehal WZ, Lo YM, Wordsworth BP, et al. HLA DR4 is a marker for rapid disease progression in primary sclerosing cholangitis. Gastroenterology. 1994;106(1):160–7.PubMedGoogle Scholar
  33. 33.
    Gow PJ, Fleming KA, Chapman RW. Primary sclerosing cholangitis associated with rheumatoid arthritis and HLA DR4: is the association a marker of patients with progressive liver disease? J Hepatol. 2001;34(4):631–5.PubMedGoogle Scholar
  34. 34.
    Boberg KM, Spurkland A, Rocca G, et al. The HLA-DR3, DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis. Scand J Gastroenterol. 2001;36(8):886–90.PubMedGoogle Scholar
  35. 35.
    Sheth S, Shea JC, Bishop MD, et al. Increased prevalence of CFTR mutations and variants and decreased chloride secretion in primary sclerosing cholangitis. Hum Genet. 2003;113(3):286–92.PubMedGoogle Scholar
  36. 36.
    McGill JM, Williams DM, Hunt CM. Survey of cystic fibrosis transmembrane conductance regulator genotypes in primary sclerosing cholangitis. Dig Dis Sci. 1996;41(3):540–2.PubMedGoogle Scholar
  37. 37.
    Girodon E, Sternberg D, Chazouilleres O, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene defects in patients with primary sclerosing cholangitis. J Hepatol. 2002;37(2):192–7.PubMedGoogle Scholar
  38. 38.
    Neri TM, Cavestro GM, Seghini P, et al. Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population. Dig Liver Dis. 2003;35(8):571–6.PubMedGoogle Scholar
  39. 39.
    Gallegos-Orozco JF, E Yurk C, Wang N, et al. Lack of association of common cystic fibrosis transmembrane conductance regulator gene mutations with primary sclerosing cholangitis. Am J Gastroenterol. 2005;100(4):874–8.PubMedGoogle Scholar
  40. 40.
    Pall H, Zielenski J, Jonas MM, et al. Primary sclerosing cholangitis in childhood is associated with abnormalities in cystic fibrosis-mediated chloride channel function. J Pediatr. 2007;151(3):255–9.PubMedGoogle Scholar
  41. 41.
    Kaplan GG, Laupland KB, Butzner D, Urbanski SJ, Lee SS. The burden of large and small duct primary sclerosing cholangitis in adults and children: a population-based analysis. Am J Gastroenterol. 2007;102(5):1042–9.PubMedGoogle Scholar
  42. 42.
    Charatcharoenwitthaya P, Lindor KD. Primary sclerosing cholangitis: diagnosis and management. Curr Gastroenterol Rep. 2006;8(1):75–82.PubMedGoogle Scholar
  43. 43.
    Bjornsson E, Angulo P. Cholangiocarcinoma in young individuals with and without primary sclerosing cholangitis. Am J Gastroenterol. 2007;102(8):1677–82.PubMedGoogle Scholar
  44. 44.
    Cullen SN, Chapman RW. Review article: current management of primary sclerosing cholangitis. Aliment Pharmacol Ther. 2005;21(8):933–48.PubMedGoogle Scholar
  45. 45.
    Dickson ER, Murtaugh PA, Wiesner RH, et al. Primary sclerosing cholangitis: refinement and validation of survival models. Gastroenterology. 1992;103(6):1893–901.PubMedGoogle Scholar
  46. 46.
    Kim WR, Therneau TM, Wiesner RH, et al. A revised natural history model for primary sclerosing cholangitis. Mayo Clin Proc. 2000;75(7):688–94.PubMedGoogle Scholar
  47. 47.
    Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33(2):464–70.PubMedGoogle Scholar
  48. 48.
    Chapman RW, Cottone M, Selby WS, Shepherd HA, Sherlock S, Jewell DP. Serum autoantibodies, ulcerative colitis and primary sclerosing cholangitis. Gut. 1986;27(1):86–91.PubMedGoogle Scholar
  49. 49.
    Mulder AH, Horst G, Haagsma EB, Limburg PC, Kleibeuker JH, Kallenberg CG. Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver diseases. Hepatology. 1993;17(3):411–7.PubMedGoogle Scholar
  50. 50.
    Bansi D, Chapman R, Fleming K. Antineutrophil cytoplasmic antibodies in chronic liver diseases: prevalence, titre, specificity and IgG subclass. J Hepatol. 1996;24(5):581–6.PubMedGoogle Scholar
  51. 51.
    Chapman RW. The enigma of anti-neutrophil antibodies in ulcerative colitis primary sclerosing cholangitis: important genetic marker or epiphenomenon? Hepatology. 1995;21(5):1473–4.PubMedGoogle Scholar
  52. 52.
    Wiesner RH. Current concepts in primary sclerosing cholangitis. Mayo Clin Proc. 1994;69(10):969–82.PubMedGoogle Scholar
  53. 53.
    Bilbao MK, Dotter CT, Lee TG, Katon RM. Complications of endoscopic retrograde cholangiopancreatography (ERCP). A study of 10, 000 cases. Gastroenterology. 1976;70(3):314–20.PubMedGoogle Scholar
  54. 54.
    Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996;335(13):909–18.PubMedGoogle Scholar
  55. 55.
    Talwalkar JA, Angulo P, Johnson CD, Petersen BT, Lindor KD. Cost-minimization analysis of MRC versus ERCP for the diagnosis of primary sclerosing cholangitis. Hepatology. 2004;40(1):39–45.PubMedGoogle Scholar
  56. 56.
    Bangarulingam SY, Gossard AA, Petersen BT, Ott BJ, Lindor KD. Complications of endoscopic retrograde cholangiopancreatography in primary sclerosing cholangitis. Am J Gastroenterol. 2009;104(4):855–60.PubMedGoogle Scholar
  57. 57.
    Mehta SN, Reinhold C, Barkun AN. Magnetic resonance cholangiopancreatography. Gastrointest Endosc Clin N Am. 1997;7(2):247–70.PubMedGoogle Scholar
  58. 58.
    Fulcher AS, Turner MA, Franklin KJ, et al. Primary sclerosing cholangitis: evaluation with MR cholangiography-a case-control study. Radiology. 2000;215(1):71–80.PubMedGoogle Scholar
  59. 59.
    Moff SL, Kamel IR, Eustace J, et al. Diagnosis of primary sclerosing cholangitis: a blinded comparative study using magnetic resonance cholangiography and endoscopic retrograde cholangiography. Gastrointest Endosc. 2006;64(2):219–23.PubMedGoogle Scholar
  60. 60.
    Petrovic BD, Nikolaidis P, Hammond NA, et al. Correlation Between Findings on MRCP and Gadolinium-Enhanced MR of the Liver and a Survival Model for Primary Sclerosing Cholangitis. Dig Dis Sci. 2007;52(12):3499–506.Google Scholar
  61. 61.
    Angulo P, Pearce DH, Johnson CD, et al. Magnetic resonance cholangiography in patients with biliary disease: its role in primary sclerosing cholangitis. J Hepatol. 2000;33(4):520–7.PubMedGoogle Scholar
  62. 62.
    Ludwig J. Surgical pathology of the syndrome of primary sclerosing cholangitis. Am J Surg Pathol. 1989;13 Suppl 1:43–9.PubMedGoogle Scholar
  63. 63.
    Scheuer PJ. Ludwig Symposium on biliary disorders – part II. Pathologic features and evolution of primary biliary cirrhosis and primary sclerosing cholangitis. Mayo Clin Proc. 1998;73(2):179–83.PubMedGoogle Scholar
  64. 64.
    Burak KW, Angulo P, Lindor KD. Is there a role for liver biopsy in primary sclerosing cholangitis? Am J Gastroenterol. 2003;98(5):1155–8.PubMedGoogle Scholar
  65. 65.
    Gossard AA, Angulo P, Lindor KD. Secondary sclerosing cholangitis: a comparison to primary sclerosing cholangitis. Am J Gastroenterol. 2005;100(6):1330–3.PubMedGoogle Scholar
  66. 66.
    Ludwig J, Barham SS, LaRusso NF, Elveback LR, Wiesner RH, McCall JT. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology. 1981;1(6):632–40.PubMedGoogle Scholar
  67. 67.
    Angulo P, Lindor KD. Primary sclerosing cholangitis. Hepatology. 1999;30(1):325–32.PubMedGoogle Scholar
  68. 68.
    Lindor K. Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. N Engl J Med. 2007;357(15):1524–9.PubMedGoogle Scholar
  69. 69.
    Lazaridis KN, Gores GJ, Lindor KD. Ursodeoxycholic acid ‘mechanisms of action and clinical use in hepatobiliary disorders. J Hepatol. 2001;35(1):134–46.PubMedGoogle Scholar
  70. 70.
    Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology. 2002;36(3):525–31.PubMedGoogle Scholar
  71. 71.
    Bachrach WH, Hofmann AF. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Part II. Dig Dis Sci. 1982;27(9):833–56.PubMedGoogle Scholar
  72. 72.
    Beuers U, Spengler U, Kruis W, et al. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial. Hepatology. 1992;16(3):707–14.PubMedGoogle Scholar
  73. 73.
    Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med. 1997;336(10):691–5.PubMedGoogle Scholar
  74. 74.
    O’Brien CB, Senior JR, Arora-Mirchandani R, Batta AK, Salen G. Ursodeoxycholic acid for the treatment of primary sclerosing cholangitis: a 30-month pilot study. Hepatology. 1991;14(5):838–47.PubMedGoogle Scholar
  75. 75.
    Stiehl A, Walker S, Stiehl L, Rudolph G, Hofmann WJ, Theilmann L. Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period. J Hepatol. 1994;20(1):57–64.PubMedGoogle Scholar
  76. 76.
    De Maria N, Colantoni A, Rosenbloom E, Van Thiel DH. Ursodeoxycholic acid does not improve the clinical course of primary sclerosing cholangitis over a 2-year period. Hepatogastroenterology. 1996;43(12):1472–9.PubMedGoogle Scholar
  77. 77.
    van Hoogstraten HJ, Wolfhagen FH, van de Meeberg PC, et al. Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses. J Hepatol. 1998;29(3):417–23.PubMedGoogle Scholar
  78. 78.
    Mitchell SA, Bansi DS, Hunt N, Von Bergmann K, Fleming KA, Chapman RW. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology. 2001;121(4):900–7.PubMedGoogle Scholar
  79. 79.
    Harnois DM, Angulo P, Jorgensen RA, Larusso NF, Lindor KD. High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis. Am J Gastroenterol. 2001;96(5):1558–62.PubMedGoogle Scholar
  80. 80.
    Okolicsanyi L, Groppo M, Floreani A, et al. Treatment of primary sclerosing cholangitis with low-dose ursodeoxycholic acid: results of a retrospective Italian multicentre survey. Dig Liver Dis. 2003;35(5):325–31.PubMedGoogle Scholar
  81. 81.
    Olsson R, Boberg KM, de Muckadell OS, et al. High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study. Gastroenterology. 2005;129(5):1464–72.PubMedGoogle Scholar
  82. 82.
    Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50(3):808–14.Google Scholar
  83. 83.
    Angulo P, Batts KP, Jorgensen RA, LaRusso NA, Lindor KD. Oral budesonide in the treatment of primary sclerosing cholangitis. Am J Gastroenterol. 2000;95(9):2333–7.PubMedGoogle Scholar
  84. 84.
    Talwalkar JA, Angulo P, Keach JC, Petz JL, Jorgensen RA, Lindor KD. Mycophenolate mofetil for the treatment of primary sclerosing cholangitis. Am J Gastroenterol. 2005;100(2):308–12.PubMedGoogle Scholar
  85. 85.
    Talwalkar JA, Gossard AA, Keach JC, Jorgensen RA, Petz JL, Lindor RN. Tacrolimus for the treatment of primary sclerosing cholangitis. Liver Int. 2007;27(4):451–3.PubMedGoogle Scholar
  86. 86.
    Knox TA, Kaplan MM. A double-blind controlled trial of oral-pulse methotrexate therapy in the treatment of primary sclerosing cholangitis. Gastroenterology. 1994;106(2):494–9.PubMedGoogle Scholar
  87. 87.
    Sterling RK, Salvatori JJ, Luketic VA, et al. A prospective, randomized-controlled pilot study of ursodeoxycholic acid combined with mycophenolate mofetil in the treatment of primary sclerosing cholangitis. Aliment Pharmacol Ther. 2004;20(9):943–9.PubMedGoogle Scholar
  88. 88.
    Van Thiel DH, Carroll P, Abu-Elmagd K, et al. Tacrolimus (FK 506), a treatment for primary sclerosing cholangitis: results of an open-label preliminary trial. Am J Gastroenterol. 1995;90(3):455–9.PubMedGoogle Scholar
  89. 89.
    Kita R, Kita-Sasai Y, Hanaoka I, et al. Beneficial effect of bezafibrate on primary sclerosing cholangitis (three case reports). Am J Gastroenterol. 2002;97(7):1849–51.PubMedGoogle Scholar
  90. 90.
    Olsson R, Broome U, Danielsson A, et al. Colchicine treatment of primary sclerosing cholangitis. Gastroenterology. 1995;108(4):1199–203.PubMedGoogle Scholar
  91. 91.
    Duchini A, Younossi ZM, Saven A, Bordin GM, Knowles HJ, Pockros PJ. An open-label pilot trial of cladibrine (2-cholordeoxyadenosine) in patients with primary sclerosing cholangitis. J Clin Gastroenterol. 2000;31(4):292–6.PubMedGoogle Scholar
  92. 92.
    Sandborn WJ, Wiesner RH, Tremaine WJ, Larusso NF. Ulcerative colitis disease activity following treatment of associated primary sclerosing cholangitis with cyclosporin. Gut. 1993;34(2):242–6.PubMedGoogle Scholar
  93. 93.
    Epstein MP, Kaplan MM. A pilot study of etanercept in the treatment of primary sclerosing cholangitis. Dig Dis Sci. 2004;49(1):1–4.PubMedGoogle Scholar
  94. 94.
    Hommes DW, Erkelens W, Ponsioen C, et al. A double-blind, placebo-controlled, randomized study of infliximab in primary sclerosing cholangitis. J Clin Gastroenterol. 2008;42(5):522–6.Google Scholar
  95. 95.
    Angulo P, Bharucha AE, Jorgensen RA, et al. Oral nicotine in treatment of primary sclerosing cholangitis: a pilot study. Dig Dis Sci. 1999;44(3):602–7.PubMedGoogle Scholar
  96. 96.
    Vleggaar FP, van Buuren HR, van Berge Henegouwen GP, Hop WC, van Erpecum KJ. No beneficial effects of transdermal nicotine in patients with primary sclerosing cholangitis: results of a randomized double-blind placebo-controlled cross-over study. Eur J Gastroenterol Hepatol. 2001;13(2):171–5.PubMedGoogle Scholar
  97. 97.
    LaRusso NF, Wiesner RH, Ludwig J, MacCarty RL, Beaver SJ, Zinsmeister AR. Prospective trial of penicillamine in primary sclerosing cholangitis. Gastroenterology. 1988;95(4):1036–42.PubMedGoogle Scholar
  98. 98.
    Bharucha AE, Jorgensen R, Lichtman SN, LaRusso NF, Lindor KD. A pilot study of pentoxifylline for the treatment of primary sclerosing cholangitis. Am J Gastroenterol. 2000;95(9):2338–42.PubMedGoogle Scholar
  99. 99.
    Angulo P, MacCarty RL, Sylvestre PB, et al. Pirfenidone in the treatment of primary sclerosing cholangitis. Dig Dis Sci. 2002;47(1):157–61.PubMedGoogle Scholar
  100. 100.
    Angulo P, Jorgensen RA, Kowdley KV, Lindor KD. Silymarin in the treatment of patients with primary sclerosing cholangitis: an open-label pilot study. Dig Dis Sci. 2007;53(6):1716–20.Google Scholar
  101. 101.
    Fong DG, Lindor KD. Future directions in the medical treatment of primary sclerosing cholangitis: the need for combination drug therapy. Am J Gastroenterol. 2000;95(8):1861–2.PubMedGoogle Scholar
  102. 102.
    Kyokane K, Ichihara T, Horisawa M, et al. Successful treatment of primary sclerosing cholangitis with cyclosporine and corticosteroid. Hepatogastroenterology. 1994;41(5):449–52.PubMedGoogle Scholar
  103. 103.
    Tada S, Ebinuma H, Saito H, Hibi T. Therapeutic benefit of ­sulfasalazine for patients with primary sclerosing cholangitis. J Gastroenterol. 2006;41(4):388–9.PubMedGoogle Scholar
  104. 104.
    Schramm C, Schirmacher P, Helmreich-Becker I, Gerken G, zum Buschenfelde KH, Lohse AW. Combined therapy with azathioprine, prednisolone, and ursodiol in patients with primary sclerosing cholangitis. A case series. Ann Intern Med. 1999;131(12):943–6.PubMedGoogle Scholar
  105. 105.
    Lindor KD, Wiesner RH, Colwell LJ, Steiner B, Beaver S, LaRusso NF. The combination of prednisone and colchicine in patients with primary sclerosing cholangitis. Am J Gastroenterol. 1991;86(1):57–61.PubMedGoogle Scholar
  106. 106.
    van Hoogstraten HJ, Vleggaar FP, Boland GJ, et al. Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double-blind pilot study. Belgian-Dutch PSC Study Group. Am J Gastroenterol. 2000;95(8):2015–22.PubMedGoogle Scholar
  107. 107.
    Lindor KD, Jorgensen RA, Anderson ML, Gores GJ, Hofmann AF, LaRusso NF. Ursodeoxycholic acid and methotrexate for primary sclerosing cholangitis: a pilot study. Am J Gastroenterol. 1996;91(3):511–5.PubMedGoogle Scholar
  108. 108.
    Farkkila M, Karvonen AL, Nurmi H, et al. Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo-controlled trial. Hepatology. 2004;40(6):1379–86.PubMedGoogle Scholar
  109. 109.
    Silveira MG, Torok NJ, Gossard AA, et al. Minocycline in the treatment of patients with primary sclerosing cholangitis: results of a pilot study. Am J Gastroenterol. 2009;104(1):83–8.PubMedGoogle Scholar
  110. 110.
    Pall H, Zaman MM, Andersson C, Freedman SD. Decreased peroxisome proliferator activated receptor alpha is associated with bile duct injury in cystic fibrosis transmembrane conductance regulator-/- mice. J Pediatr Gastroenterol Nutr. 2006;42(3):275–81.PubMedGoogle Scholar
  111. 111.
    Fickert P, Wagner M, Marschall HU, et al. 24-norUrsodeoxycholic acid is superior to ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology. 2006;130(2):465–81.PubMedGoogle Scholar
  112. 112.
    Warner FJ, Lubel JS, McCaughan GW, Angus PW. Liver fibrosis: a balance of ACEs? Clin Sci (Lond). 2007;113(3):109–18.Google Scholar
  113. 113.
    Molteni A, Ward WF, Ts’ao CH, et al. Cytostatic properties of some angiotensin I converting enzyme inhibitors and of angiotensin II type I receptor antagonists. Curr Pharm Des. 2003;9(9):751–61.PubMedGoogle Scholar
  114. 114.
    Paizis G, Gilbert RE, Cooper ME, et al. Effect of angiotensin II type 1 receptor blockade on experimental hepatic fibrogenesis. J Hepatol. 2001;35(3):376–85.PubMedGoogle Scholar
  115. 115.
    Jonsson JR, Clouston AD, Ando Y, et al. Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology. 2001;121(1):148–55.PubMedGoogle Scholar
  116. 116.
    Croquet V, Moal F, Veal N, et al. Hemodynamic and antifibrotic effects of losartan in rats with liver fibrosis and/or portal hypertension. J Hepatol. 2002;37(6):773–80.PubMedGoogle Scholar
  117. 117.
    Yoshiji H, Kuriyama S, Yoshii J, et al. Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats. Hepatology. 2001;34(4 Pt 1):745–50.PubMedGoogle Scholar
  118. 118.
    Ohishi T, Saito H, Tsusaka K, et al. Anti-fibrogenic effect of an angiotensin converting enzyme inhibitor on chronic carbon tetrachloride-induced hepatic fibrosis in rats. Hepatol Res. 2001;21(2):147–58.PubMedGoogle Scholar
  119. 119.
    de Cavanagh EM, Inserra F, Toblli J, Stella I, Fraga CG, Ferder L. Enalapril attenuates oxidative stress in diabetic rats. Hypertension. 2001;38(5):1130–6.PubMedGoogle Scholar
  120. 120.
    Toblli JE, Ferder L, Stella I, Angerosa M, Inserra F. Enalapril prevents fatty liver in nephrotic rats. J Nephrol. 2002;15(4):358–67.PubMedGoogle Scholar
  121. 121.
    Terui Y, Saito T, Watanabe H, et al. Effect of angiotensin receptor antagonist on liver fibrosis in early stages of chronic hepatitis C. Hepatology. 2002;36(4 Pt 1):1022.PubMedGoogle Scholar
  122. 122.
    Yokohama S, Yoneda M, Haneda M, et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology. 2004;40(5):1222–5.PubMedGoogle Scholar
  123. 123.
    Yoshiji H, Noguchi R, Fukui H. Combined effect of an ACE inhibitor, perindopril, and interferon on liver fibrosis markers in patients with chronic hepatitis C. J Gastroenterol. 2005;40(2):215–6.PubMedGoogle Scholar
  124. 124.
    Rimola A, Londono MC, Guevara G, et al. Beneficial effect of angiotensin-blocking agents on graft fibrosis in hepatitis C recurrence after liver transplantation. Transplantation. 2004;78(5):686–91.PubMedGoogle Scholar
  125. 125.
    Halilbasic E, Fiorotto R, Fickert P, et al. Side chain structure determines unique physiologic and therapeutic properties of norursodeoxycholic acid in Mdr2-/- mice. Hepatology. 2009;49(6):1972–81.PubMedGoogle Scholar
  126. 126.
    Glaser SS, Alpini G. Activation of the cholehepatic shunt as a potential therapy for primary sclerosing cholangitis. Hepatology. 2009;49(6):1795–7.PubMedGoogle Scholar
  127. 127.
    Kaya M, Petersen BT, Angulo P, et al. Balloon dilation compared to stenting of dominant strictures in primary sclerosing cholangitis. Am J Gastroenterol. 2001;96(4):1059–66.PubMedGoogle Scholar
  128. 128.
    Linder S, Soderlund C. Endoscopic therapy in primary sclerosing cholangitis: outcome of treatment and risk of cancer. Hepatogastroentero­logy. 2001;48(38):387–92.PubMedGoogle Scholar
  129. 129.
    Stiehl A, Rudolph G, Sauer P, et al. Efficacy of ursodeoxycholic acid treatment and endoscopic dilation of major duct stenoses in primary sclerosing cholangitis. An 8-year prospective study. J Hepatol. 1997;26(3):560–6.PubMedGoogle Scholar
  130. 130.
    Baluyut AR, Sherman S, Lehman GA, Hoen H, Chalasani N. Impact of endoscopic therapy on the survival of patients with primary sclerosing cholangitis. Gastrointest Endosc. 2001;53(3):308–12.PubMedGoogle Scholar
  131. 131.
    McEntee G, Wiesner RH, Rosen C, Cooper J, Wahlstrom E. A comparative study of patients undergoing liver transplantation for primary sclerosing cholangitis and primary biliary cirrhosis. Transplant Proc. 1991;23(1 Pt 2):1563–4.PubMedGoogle Scholar
  132. 132.
    Muiesan P, Shanmugam RP, Devlin J, et al. Orthotopic liver transplantation for primary sclerosing cholangitis. Transplant Proc. 1994;26(6):3574–6.PubMedGoogle Scholar
  133. 133.
    Farges O, Malassagne B, Sebagh M, Bismuth H. Primary sclerosing cholangitis: liver transplantation or biliary surgery. Surgery. 1995;117(2):146–55.PubMedGoogle Scholar
  134. 134.
    Narumi S, Roberts JP, Emond JC, Lake J, Ascher NL. Liver transplantation for sclerosing cholangitis. Hepatology. 1995;22(2):451–7.PubMedGoogle Scholar
  135. 135.
    Ahrendt SA, Pitt HA, Kalloo AN, et al. Primary sclerosing cholangitis: resect, dilate, or transplant? Ann Surg. 1998;227(3):412–23.PubMedGoogle Scholar
  136. 136.
    Nashan B, Schlitt HJ, Tusch G, et al. Biliary malignancies in primary sclerosing cholangitis: timing for liver transplantation. Hepatology. 1996;23(5):1105–11.PubMedGoogle Scholar
  137. 137.
    Roberts MS, Angus DC, Bryce CL, Valenta Z, Weissfeld L. Survival after liver transplantation in the United States: a disease-specific analysis of the UNOS database. Liver Transpl. 2004;10(7):886–97.PubMedGoogle Scholar
  138. 138.
    Merion RM. When is a patient too well and when is a patient too sick for a liver transplant? Liver Transpl. 2004;10(10 Suppl 2):S69–73.PubMedGoogle Scholar
  139. 139.
    Khettry U, Keaveny A, Goldar-Najafi A, et al. Liver transplantation for primary sclerosing cholangitis: a long-term clinicopathologic study. Hum Pathol. 2003;34(11):1127–36.PubMedGoogle Scholar
  140. 140.
    Brandsaeter B, Schrumpf E, Clausen OP, Abildgaard A, Hafsahl G, Bjoro K. Recurrent sclerosing cholangitis or ischemic bile duct lesions – a diagnostic challenge? Liver Transpl. 2004;10(8):1073–4.PubMedGoogle Scholar
  141. 141.
    Gordon F. Recurrent primary sclerosing cholangitis: clinical diagnosis and long-term management issues. Liver Transpl. 2006;12(11 Suppl 2):S73–5.PubMedGoogle Scholar
  142. 142.
    Tamura S, Sugawara Y, Kaneko J, Matsui Y, Togashi J, Makuuchi M. Recurrence of primary sclerosing cholangitis after living donor liver transplantation. Liver Int. 2007;27(1):86–94.PubMedGoogle Scholar
  143. 143.
    Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol. 2004;99(3):523–6.PubMedGoogle Scholar
  144. 144.
    Harnois DM, Gores GJ, Ludwig J, Steers JL, LaRusso NF, Wiesner RH. Are patients with cirrhotic stage primary sclerosing cholangitis at risk for the development of hepatocellular cancer? J Hepatol. 1997;27(3):512–6.PubMedGoogle Scholar
  145. 145.
    Wee A, Ludwig J, Coffey Jr RJ, LaRusso NF, Wiesner RH. Hepatobiliary carcinoma associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hum Pathol. 1985;16(7):719–26.PubMedGoogle Scholar
  146. 146.
    Kaya M, de Groen PC, Angulo P, et al. Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience. Am J Gastroenterol. 2001;96(4):1164–9.PubMedGoogle Scholar
  147. 147.
    Boberg KM, Bergquist A, Mitchell S, et al. Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation. Scand J Gastroenterol. 2002;37(10):1205–11.PubMedGoogle Scholar
  148. 148.
    Ahrendt SA, Pitt HA, Nakeeb A, et al. Diagnosis and management of cholangiocarcinoma in primary sclerosing cholangitis. J Gastrointest Surg. 1999;3(4):357–67. discussion 367–358.PubMedGoogle Scholar
  149. 149.
    Bergquist A, Ekbom A, Olsson R, et al. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol. 2002;36(3):321–7.PubMedGoogle Scholar
  150. 150.
    Fleming KA, Boberg KM, Glaumann H, Bergquist A, Smith D, Clausen OP. Biliary dysplasia as a marker of cholangiocarcinoma in primary sclerosing cholangitis. J Hepatol. 2001;34(3):360–5.PubMedGoogle Scholar
  151. 151.
    Bergquist A, Glaumann H, Stal P, Wang GS, Broome U. Biliary dysplasia, cell proliferation and nuclear DNA-fragmentation in primary sclerosing cholangitis with and without cholangiocarcinoma. J Intern Med. 2001;249(1):69–75.PubMedGoogle Scholar
  152. 152.
    Ramage JK, Donaghy A, Farrant JM, Iorns R, Williams R. Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Gastroenterology. 1995;108(3):865–9.PubMedGoogle Scholar
  153. 153.
    Hultcrantz R, Olsson R, Danielsson A, et al. A 3-year prospective study on serum tumor markers used for detecting cholangiocarcinoma in patients with primary sclerosing cholangitis. J Hepatol. 1999;30(4):669–73.PubMedGoogle Scholar
  154. 154.
    Levy C, Lymp J, Angulo P, Gores GJ, Larusso N, Lindor KD. The value of serum CA 19–9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis. Dig Dis Sci. 2005;50(9):1734–40.PubMedGoogle Scholar
  155. 155.
    Fevery J, Verslype C, Lai G, Aerts R, Van Steenbergen W. Incidence, diagnosis, and therapy of cholangiocarcinoma in patients with primary sclerosing cholangitis. Dig Dis Sci. 2007;52(11):3123–35.Google Scholar
  156. 156.
    Brandsaeter B, Isoniemi H, Broome U, et al. Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy. J Hepatol. 2004;40(5):815–22.PubMedGoogle Scholar
  157. 157.
    Ghali P, Marotta PJ, Yoshida EM, et al. Liver transplantation for incidental cholangiocarcinoma: analysis of the Canadian experience. Liver Transpl. 2005;11(11):1412–6.PubMedGoogle Scholar
  158. 158.
    Robles R, Figueras J, Turrion VS, et al. Spanish experience in liver transplantation for hilar and peripheral cholangiocarcinoma. Ann Surg. 2004;239(2):265–71.PubMedGoogle Scholar
  159. 159.
    Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation. 2000;69(8):1633–7.PubMedGoogle Scholar
  160. 160.
    Rea DJ, Heimbach JK, Rosen CB, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005;242(3):451–8. discussion 458–461.PubMedGoogle Scholar
  161. 161.
    Sudan D, DeRoover A, Chinnakotla S, et al. Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant. 2002;2(8):774–9.PubMedGoogle Scholar
  162. 162.
    Heimbach JK, Gores GJ, Nagorney DM, Rosen CB. Liver transplantation for perihilar cholangiocarcinoma after aggressive neoadjuvant therapy: a new paradigm for liver and biliary malignancies? Surgery. 2006;140(3):331–4.PubMedGoogle Scholar
  163. 163.
    Charatcharoenwitthaya P, Enders FB, Halling KC, Lindor KD. Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis. Hepatology. 2008;48(4):1106–17.PubMedGoogle Scholar
  164. 164.
    Moreno Luna LE, Kipp B, Halling KC, et al. Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures. Gastroenterology. 2006;131(4):1064–72.PubMedGoogle Scholar
  165. 165.
    Rudolph G, Kloeters-Plachky P, Rost D, Stiehl A. The incidence of cholangiocarcinoma in primary sclerosing cholangitis after long-time treatment with ursodeoxycholic acid. Eur J Gastroenterol Hepatol. 2007;19(6):487–91.PubMedGoogle Scholar
  166. 166.
    Bergquist A, Glaumann H, Persson B, Broome U. Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study. Hepatology. 1998;27(2):311–6.PubMedGoogle Scholar
  167. 167.
    Broome U, Chapman RW. Ulcerative colitis: sclerosing cholangitis today, cancer tomorrow? Gut. 1997;41(4):571–2.PubMedGoogle Scholar
  168. 168.
    Jayaram H, Satsangi J, Chapman RW. Increased colorectal neoplasia in chronic ulcerative colitis complicated by primary sclerosing cholangitis: fact or fiction? Gut. 2001;48(3):430–4.PubMedGoogle Scholar
  169. 169.
    Broome U, Lofberg R, Veress B, Eriksson LS. Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential. Hepatology. 1995;22(5):1404–8.PubMedGoogle Scholar
  170. 170.
    Broome U, Lindberg G, Lofberg R. Primary sclerosing cholangitis in ulcerative colitis—a risk factor for the development of dysplasia and DNA aneuploidy? Gastroenterology. 1992;102(6):1877–80.PubMedGoogle Scholar
  171. 171.
    Kornfeld D, Ekbom A, Ihre T. Is there an excess risk for colorectal cancer in patients with ulcerative colitis and concomitant primary ­sclerosing cholangitis? A population based study. Gut. 1997;41(4):522–5.PubMedGoogle Scholar
  172. 172.
    Loftus Jr EV, Sandborn WJ, Tremaine WJ, et al. Risk of colorectal neoplasia in patients with primary sclerosing cholangitis. Gastroenterology. 1996;110(2):432–40.PubMedGoogle Scholar
  173. 173.
    Nuako KW, Ahlquist DA, Sandborn WJ, Mahoney DW, Siems DM, Zinsmeister AR. Primary sclerosing cholangitis and colorectal carcinoma in patients with chronic ulcerative colitis: a case-control study. Cancer. 1998;82(5):822–6.PubMedGoogle Scholar
  174. 174.
    Loftus Jr EV, Aguilar HI, Sandborn WJ, et al. Risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis following orthotopic liver transplantation. Hepatology. 1998;27(3):685–90.PubMedGoogle Scholar
  175. 175.
    Tung BY, Emond MJ, Haggitt RC, et al. Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Ann Intern Med. 2001;134(2):89–95.PubMedGoogle Scholar
  176. 176.
    Pardi DS, Loftus Jr EV, Kremers WK, Keach J, Lindor KD. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology. 2003;124(4):889–93.PubMedGoogle Scholar
  177. 177.
    Mir-Madjlessi SH, Farmer RG, Sivak Jr MV. Bile duct carcinoma in patients with ulcerative colitis. Relationship to sclerosing cholangitis: report of six cases and review of the literature. Dig Dis Sci. 1987;32(2):145–54.PubMedGoogle Scholar
  178. 178.
    Lewis JT, Talwalkar JA, Rosen CB, Smyrk TC, Abraham SC. Prevalence and risk factors for gallbladder neoplasia in patients with primary sclerosing cholangitis: evidence for a metaplasia-dysplasia-carcinoma sequence. Am J Surg Pathol. 2007;31(6):907–13.PubMedGoogle Scholar
  179. 179.
    Leung UC, Wong PY, Roberts RH, Koea JB. Gall bladder polyps in sclerosing cholangitis: does the 1-cm rule apply? ANZ J Surg. 2007;77(5):355–7.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Gastroenterology and HepatologyMayo ClinicRochesterUSA

Personalised recommendations