Digestive and Liver Disease
Volume 42, Issue 6 , Pages 390-400 , June 2010

Update on primary sclerosing cholangitis

Received 17 December 2009 ,Accepted 17 January 2010.

References 

  1. Ludwig J, MacCarty RL, LaRusso NF, et al. Intrahepatic cholangiectases and large-duct obliteration in primary sclerosing cholangitis. Hepatology. 1986;6:560–568
  2. Wiesner RH, LaRusso NF. Clinicopathologic features of the syndrome of primary sclerosing cholangitis. Gastroenterology. 1980;79:200–206
  3. Olsson R, Hagerstrand I, Broome U, et al. Sampling variability of percutaneous liver biopsy in primary sclerosing cholangitis. J Clin Pathol. 1995;48:933–935
  4. Tischendorf JJ, Hecker H, Kruger M, et al. Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am J Gastroenterol. 2007;102:107–114
  5. Bjornsson E, Lindqvist-Ottosson J, Asztely M, et al. Dominant strictures in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2004;99:502–508
  6. Rudolph G, Gotthardt D, Kloters-Plachky P, et al. Influence of dominant bile duct stenoses and biliary infections on outcome in primary sclerosing cholangitis. J Hepatol. 2009;51:149–155
  7. Porayko MK, LaRusso NF. Wiesner RH Primary sclerosing cholangitis: a progressive disease?. Semin Liver Dis. 1991;11:18–25
  8. Wiesner RH. Liver transplantation for primary sclerosing cholangitis: timing, outcome, impact of inflammatory bowel disease and recurrence of disease. Best Pract Res Clin Gastroenterol. 2001;15:667–680
  9. Farrant JM, Hayllar KM, Wilkinson ML, et al. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology. 1991;100:1710–1717
  10. Broome U, Olsson R, Loof L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996;38:610–615
  11. Aadland E, Schrumpf E, Fausa O, et al. Primary sclerosing cholangitis: a long-term follow-up study. Scand J Gastroenterol. 1987;22:655–664
  12. Boberg KM, Aadland E, Jahnsen J, et al. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol. 1998;33:99–103
  13. Kingham JG, Kochar N, Gravenor MB. Incidence, clinical patterns, and outcomes of primary sclerosing cholangitis in South Wales, United Kingdom. Gastroenterology. 2004;126:1929–1930
  14. Bambha K, Kim WR, Talwalkar J, et al. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology. 2003;125:1364–1369
  15. Escorsell A, Pares A, Rodes J, et al. Epidemiology of primary sclerosing cholangitis in Spain. J Hepatol. 1994;21:787–791
  16. Ang TL, Fock KM, Ng TM, et al. Clinical profile of primary sclerosing cholangitis in Singapore. J Gastroenterol Hepatol. 2002;17:908–913
  17. Okolicsanyi L, Fabris L, Viaggi S, et al. Primary sclerosing cholangitis: clinical presentation, natural history and prognostic variables: an Italian multicentre study. The Italian PSC Study Group. Eur J Gastroenterol Hepatol. 1996;8:685–691
  18. Kochhar R, Goenka MK, Das K, et al. Primary sclerosing cholangitis: an experience from India. J Gastroenterol Hepatol. 1996;11:429–433
  19. Takikawa H, Takamori Y, Tanaka A, et al. Analysis of 388 cases of primary sclerosing cholangitis in Japan; Presence of a subgroup without pancreatic involvement in older patients. Hepatol Res. 2004;29:153–159
  20. Takikawa H, Manabe T. Primary sclerosing cholangitis in Japan—analysis of 192 cases. J Gastroenterol. 1997;32:134–137
  21. Fausa O, Schrumpf E, Elgjo K. Relationship of inflammatory bowel disease and primary sclerosing cholangitis. Semin Liver Dis. 1991;11:31–39
  22. Saarinen S, Olerup O, Broome U. Increased frequency of autoimmune diseases in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2000;95:3195–3199
  23. Kaya M, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol. 2000;33:537–542
  24. Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929–938
  25. van Buuren HR, van Hoogstraten HJE, Terkivatan T, et al. High prevalence of autoimmune hepatitis among patients with primary sclerosing cholangitis. J Hepatol. 2000;33:543–548
  26. Miros M, Kerlin P, Walker N, et al. Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis before transplantation. Gut. 1991;32:1369–1373
  27. Helzberg JH, Petersen JM, Boyer JL. Improved survival with primary sclerosing cholangitis. A review of clinicopathologic features and comparison of symptomatic and asymptomatic patients. Gastroenterology. 1987;92:1869–1875
  28. Ataseven H, Parlak E, Yuksel I, et al. Primary sclerosing cholangitis in Turkish patients: characteristic features and prognosis. Hepatobiliary Pancreat Dis Int. 2009;8:312–315
  29. Karlsen TH, Schrumpf E, Boberg KM. Gallbladder polyps in primary sclerosing cholangitis: not so benign. Curr Opin Gastroenterol. 2008;24:395–399
  30. Soetikno RM, Lin OS, Heidenreich PA, et al. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc. 2002;56:48–54
  31. Guicciardi ME, Gores GJ. Cholestatic hepatocellular injury: what do we know and how should we proceed. J Hepatol. 2005;42:297–300
  32. Abdalian R, Heathcote EJ. Sclerosing cholangitis: a focus on secondary causes. Hepatology. 2006;44:1063–1074
  33. Bergquist A, Montgomery SM, Bahmanyar S, et al. Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 2008;6:939–943
  34. Karlsen TH, Franke A, Melum E, et al. Genome-wide association analysis in primary sclerosing cholangitis. Gastroenterology, doi:10.1053/j.gastro.2009.11.046.
  35. Schrumpf E, Fausa O, Forre O, et al. HLA antigens and immunoregulatory T cells in ulcerative colitis associated with hepatobiliary disease. Scand J Gastroenterol. 1982;17:187–191
  36. Karlsen TH, Boberg KM, Vatn M, et al. Different HLA class II associations in ulcerative colitis patients with and without primary sclerosing cholangitis. Genes Immun. 2007;8:275–278
  37. Karlsen TH, Boberg KM, Olsson M, et al. Particular genetic variants of ligands for natural killer cell receptors may contribute to the HLA associated risk of primary sclerosing cholangitis. J Hepatol. 2007;46:899–906
  38. Hov JR, Lleo A, Selmi C, et al. Genetic associations in Italian primary sclerosing cholangitis: heterogeneity across Europe defines a critical role for HLA-C. J Hepatol; in press.
  39. Guinan KJ, Cunningham RT, Meenagh A, et al. Receptor systems controlling natural killer cell function are genetically stratified in Europe. Genes Immun. 2010;11:67–78
  40. Donaldson PT, Norris S. Evaluation of the role of MHC class II alleles, haplotypes and selected amino acid sequences in primary sclerosing cholangitis. Autoimmunity. 2002;35:555–564
  41. Wiencke K, Karlsen TH, Boberg KM, et al. Primary sclerosing cholangitis is associated with extended HLA-DR3 and HLA-DR6 haplotypes. Tissue Antigens. 2007;69:161–169
  42. Spurkland A, Saarinen S, Boberg KM, et al. HLA class II haplotypes in primary sclerosing cholangitis patients from five European populations. Tissue Antigens. 1999;53:459–469
  43. Loftus EV, Harewood GC, Loftus CG, et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut. 2005;54:91–96
  44. Oshitani N, Jinno Y, Sawa Y, et al. Does colitis associated with primary sclerosing cholangitis represent an actual subset of ulcerative colitis?. Hepatogastroenterology. 2003;50:1830–1835
  45. Joo M, Abreu-e-Lima P, Farraye F, et al. Pathologic features of ulcerative colitis in patients with primary sclerosing cholangitis: a case–control study. Am J Surg Pathol. 2009;33:854–862
  46. Abdelrazeq AS, Wilson TR, Leitch DL, et al. Ileitis in ulcerative colitis: is it a backwash?. Dis Colon Rectum. 2005;48:2038–2046
  47. Zhou YQ, Chen YQ, Fisher JH, et al. Activation of the RON receptor tyrosine kinase by macrophage-stimulating protein inhibits inducible cyclooxygenase-2 expression in murine macrophages. J Biol Chem. 2002;277:38104–38110
  48. Goyette P, Lefebvre C, Ng A, et al. Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis. Mucosal Immunol. 2008;1:131–138
  49. Keitel V, Donner M, Winandy S, et al. Expression and function of the bile acid receptor TGR5 in Kupffer cells. Biochem Biophys Res Commun. 2008;372:78–84
  50. Keitel V, Cupisti K, Ullmer C, et al. The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders. Hepatology. 2009;50:861–870
  51. Beuers U. Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:318–328
  52. Blanco PG, Zaman MM, Junaidi O, et al. Induction of colitis in cftr−/− mice results in bile duct injury. Am J Physiol Gastrointest Liver Physiol. 2004;287:G491–G496
  53. 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;113:286–292
  54. 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;37:192–197
  55. 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;50:150–157
  56. 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;151:255–259
  57. Gallegos-Orozco JF, EY 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;100:874–878
  58. Hashimoto E, Lindor KD, Homburger HA, et al. Immunohistochemical characterization of hepatic lymphocytes in primary biliary cirrhosis in comparison with primary sclerosing cholangitis and autoimmune chronic active hepatitis. Mayo Clin Proc. 1993;68:1049–1055
  59. Hata K, Van Thiel DH, Herberman RB, et al. Phenotypic and functional characteristics of lymphocytes isolated from liver biopsy specimens from patients with active liver disease. Hepatology. 1992;15:816–823
  60. Cameron RG, Blendis LM, Neuman MG. Accumulation of macrophages in primary sclerosing cholangitis. Clin Biochem. 2001;34:195–201
  61. Whiteside TL, Lasky S, Si L, et al. Immunologic analysis of mononuclear cells in liver tissues and blood of patients with primary sclerosing cholangitis. Hepatology. 1985;5:468–474
  62. Ponsioen CY, Kuiper H, Ten Kate FJ, et al. Immunohistochemical analysis of inflammation in primary sclerosing cholangitis. Eur J Gastroenterol Hepatol. 1999;11:769–774
  63. Adams DH, Eksteen B. Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease. Nat Rev Immunol. 2006;6:244–251
  64. Grant AJ, Lalor PF, Salmi M, et al. Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease. Lancet. 2002;359:150–157
  65. Hillan KJ, Hagler KE, MacSween RN, et al. Expression of the mucosal vascular addressin, MAdCAM-1, in inflammatory liver disease. Liver. 1999;19:509–518
  66. Grant AJ, Lalor PF, Hubscher SG, et al. MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease). Hepatology. 2001;33:1065–1072
  67. 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;200:1511–1517
  68. Chapman RW, Cottone M, Selby WS, et al. Serum autoantibodies, ulcerative colitis and primary sclerosing cholangitis. Gut. 1986;27:86–91
  69. Mandal A, Dasgupta A, Jeffers L, et al. Autoantibodies in sclerosing cholangitis against a shared peptide in biliary and colon epithelium. Gastroenterology. 1994;106:185–192
  70. Xu B, Broome U, Ericzon BG, et al. High frequency of autoantibodies in patients with primary sclerosing cholangitis that bind biliary epithelial cells and induce expression of CD44 and production of interleukin 6. Gut. 2002;51:120–127
  71. Broome U, Grunewald J, Scheynius A, et al. Preferential V beta3 usage by hepatic T lymphocytes in patients with primary sclerosing cholangitis. J Hepatol. 1997;26:527–534
  72. Terjung B, Herzog V, Worman HJ, et al. Atypical antineutrophil cytoplasmic antibodies with perinuclear fluorescence in chronic inflammatory bowel diseases and hepatobiliary disorders colocalize with nuclear lamina proteins. Hepatology. 1998;28:332–340
  73. Terjung B, Spengler U, Sauerbruch T, et al. “Atypical p-ANCA” in IBD and hepatobiliary disorders react with a 50-kilodalton nuclear envelope protein of neutrophils and myeloid cell lines. Gastroenterology. 2000;119:310–322
  74. Billing P, Tahir S, Calfin B, et al. Nuclear localization of the antigen detected by ulcerative colitis-associated perinuclear antineutrophil cytoplasmic antibodies. Am J Pathol. 1995;147:979–987
  75. Klein R, Eisenburg J, Weber P, et al. Significance and specificity of antibodies to neutrophils detected by western blotting for the serological diagnosis of primary sclerosing cholangitis. Hepatology. 1991;14:1147–1152
  76. Terjung B, Soehne J, Lechtenberg B, et al. p-ANCA in autoimmune liver disorders recognize human beta-tubulin isotype 5 and cross-react with microbial protein FtsZ. Gut, doi:10.1136/gut.2008.157818.
  77. Smit JJ, Schinkel AH, Oude Elferink RP, et al. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell. 1993;75:451–462
  78. Trauner M, Fickert P, Wagner M. MDR3 (ABCB4) defects: a paradigm for the genetics of adult cholestatic syndromes. Semin Liver Dis. 2007;27:77–98
  79. Popov Y, Patsenker E, Fickert P, et al. Mdr2 (Abcb4)−/− mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro- and antifibrogenic genes. J Hepatol. 2005;43:1045–1054
  80. Fickert P, Fuchsbichler A, Wagner M, et al. Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology. 2004;127:261–274
  81. Fickert P, Zollner G, Fuchsbichler A, et al. Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles. Gastroenterology. 2002;123:1238–1251
  82. Nakken KE, Nygard S, Haaland T, et al. Multiple inflammatory-, tissue remodelling- and fibrosis genes are differentially transcribed in the livers of Abcb4 (−/−) mice harbouring chronic cholangitis. Scand J Gastroenterol. 2007;42:1245–1255
  83. Jacquemin E. Role of multidrug resistance 3 deficiency in pediatric and adult liver disease: one gene for three diseases. Semin Liver Dis. 2001;21:551–562
  84. Ziol M, Barbu V, Rosmorduc O, et al. ABCB4 heterozygous gene mutations associated with fibrosing cholestatic liver disease in adults. Gastroenterology. 2008;135:131–141
  85. Gotthardt D, Runz H, Keitel V, et al. A mutation in the canalicular phospholipid transporter gene, ABCB4, is associated with cholestasis, ductopenia, and cirrhosis in adults. Hepatology. 2008;48:1157–1166
  86. Melum E, Boberg KM, Franke A, et al. Variation in the MDR3 gene influences disease progression in PSC patients and disease susceptibility in epistatic interaction with polymorphism in OST-alpha gene. Hepatology. 2007;46:265A
  87. Ohishi Y, Nakamura M, Iio N, et al. Single-nucleotide polymorphism analysis of the multidrug resistance protein 3 gene for the detection of clinical progression in Japanese patients with primary biliary cirrhosis. Hepatology. 2008;48:853–862
  88. Palmer RH. Bile acids, liver injury, and liver disease. Arch Intern Med. 1972;130:606–617
  89. Wagner M, Halilbasic E, Marschall HU, et al. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. Hepatology. 2005;42:420–430
  90. Parks DJ, Blanchard SG, Bledsoe RK, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999;284:1365–1368
  91. Guo GL, Lambert G, Negishi M, et al. Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. J Biol Chem. 2003;278:45062–45071
  92. Staudinger JL, Goodwin B, Jones SA, et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA. 2001;98:3369–3374
  93. Stedman CA, Liddle C, Coulter SA, et al. Nuclear receptors constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury. Proc Natl Acad Sci USA. 2005;102:2063–2068
  94. Saini SP, Mu Y, Gong H, et al. Dual role of orphan nuclear receptor pregnane X receptor in bilirubin detoxification in mice. Hepatology. 2005;41:497–505
  95. Xie W, Radominska-Pandya A, Shi Y, et al. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci USA. 2001;98:3375–3380
  96. Karlsen TH, Lie BA, Frey Froslie K, et al. Polymorphisms in the steroid and xenobiotic receptor gene influence survival in primary sclerosing cholangitis. Gastroenterology. 2006;131:781–787
  97. Sookoian S, Castano GO, Burgueno AL, et al. The nuclear receptor PXR gene variants are associated with liver injury in nonalcoholic fatty liver disease. Pharmacogenet Genomics. 2010;20:1–8
  98. Poupon R, Ping C, Chretien Y, et al. Genetic factors of susceptibility and of severity in primary biliary cirrhosis. J Hepatol. 2008;49:1038–1045
  99. Lichtman SN, Okoruwa EE, Keku J, et al. Degradation of endogenous bacterial cell wall polymers by the muralytic enzyme mutanolysin prevents hepatobiliary injury in genetically susceptible rats with experimental intestinal bacterial overgrowth. J Clin Invest. 1992;90:1313–1322
  100. Lichtman SN, Keku J, Schwab JH, et al. Evidence for peptidoglycan absorption in rats with experimental small bowel bacterial overgrowth. Infect Immun. 1991;59:555–562
  101. Lichtman SN, Keku J, Schwab JH, et al. Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline. Gastroenterology. 1991;100:513–519
  102. Lichtman SN, Keku J, Clark RL, et al. Biliary tract disease in rats with experimental small bowel bacterial overgrowth. Hepatology. 1991;13:766–772
  103. Lichtman SN, Sartor RB, Keku J, et al. Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth. Gastroenterology. 1990;98:414–423
  104. Bo X, Broome U, Remberger M, et al. Tumour necrosis factor alpha impairs function of liver derived T lymphocytes and natural killer cells in patients with primary sclerosing cholangitis. Gut. 2001;49:131–141
  105. Berg PA, Klein R, Rocken M. Cytokines in primary biliary cirrhosis. Semin Liver Dis. 1997;17:115–123
  106. Aoki CA, Dawson K, Kenny TP, et al. Gene expression by PBMC in primary sclerosing cholangitis: evidence for dysregulation of immune mediated genes. Clin Dev Immunol. 2006;13:265–271
  107. Karrar A, Broome U, Södergren T, et al. Biliary epithelial cell antibodies link adaptive and innate immune responses in primary sclerosing cholangitis. Gastroenterology. 2007;4:1504–1514
  108. Farkkila M, Karvonen AL, Nurmi H, et al. Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo-controlled trial. Hepatology. 2004;40:1379–1386
  109. Blechacz B, Gores GJ. Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment. Hepatology. 2008;48:308–321
  110. Komichi D, Tazuma S, Nishioka T, et al. Glycochenodeoxycholate plays a carcinogenic role in immortalized mouse cholangiocytes via oxidative DNA damage. Free Radic Biol Med. 2005;39:1418–1427
  111. Forsbring M, Vik ES, Dalhus B, et al. Catalytically impaired hMYH and NEIL1 mutant proteins identified in patients with primary sclerosing cholangitis and cholangiocarcinoma. Carcinogenesis. 2009;30:1147–1154
  112. Kobayashi S, Werneburg NW, Bronk SF, et al. Interleukin-6 contributes to Mcl-1 up-regulation and TRAIL resistance via an Akt-signaling pathway in cholangiocarcinoma cells. Gastroenterology. 2005;128:2054–2065
  113. Bromberg J, Wang TC. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell. 2009;15:79–80
  114. Isomoto H, Mott JL, Kobayashi S, et al. Sustained IL-6/STAT-3 signaling in cholangiocarcinoma cells due to SOCS-3 epigenetic silencing. Gastroenterology. 2007;132:384–396
  115. Isomoto H. Epigenetic alterations associated with cholangiocarcinoma (review). Oncol Rep. 2009;22:227–232
  116. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124:263–266
  117. Guerra N, Tan YX, Joncker NT, et al. NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity. 2008;28:571–580
  118. Melum E, Karlsen TH, Schrumpf E, et al. Cholangiocarcinoma in primary sclerosing cholangitis is associated with NKG2D polymorphisms. Hepatology. 2008;47:90–96
  119. Hayashi T, Imai K, Morishita Y, et al. Identification of the NKG2D haplotypes associated with natural cytotoxic activity of peripheral blood lymphocytes and cancer immunosurveillance. Cancer Res. 2006;66:563–570
  120. Boberg KM, Bergquist A, Mitchell S, et al. Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation. Scand J Gastroenterol. 2002;37:1205–1211
  121. Ahrendt SA, Pitt HA, Nakeeb A, et al. Diagnosis and management of cholangiocarcinoma in primary sclerosing cholangitis. J Gastrointest Surg. 1999;3:357–367discussion 67–68
  122. MacCarty RL, LaRusso NF, Wiesner RH, et al. Primary sclerosing cholangitis: findings on cholangiography and pancreatography. Radiology. 1983;149:39–44
  123. EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51:237–267
  124. Chapman RW, Fevery J, Kalloo AN, et al. AASLD guidelines: diagnosis and management of primary sclerosing cholangitis (PSC). Hepatology. 2010;51:660–678
  125. 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;33:520–527
  126. 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;64:219–223
  127. Vitellas KM, El-Dieb A, Vaswani KK, et al. MR cholangiopancreatography in patients with primary sclerosing cholangitis: interobserver variability and comparison with endoscopic retrograde cholangiopancreatography. AJR Am J Roentgenol. 2002;179:399–407
  128. Webster GJ, Pereira SP, Chapman RW. Autoimmune pancreatitis/IgG4-associated cholangitis and primary sclerosing cholangitis—overlapping or separate diseases?. J Hepatol. 2009;51:398–402
  129. Bjornsson E. Immunoglobulin G4-associated cholangitis. Curr Opin Gastroenterol. 2008;24:389–394
  130. Mendes FD, Jorgensen R, Keach J, et al. Elevated serum IgG4 concentration in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2006;101:2070–2075
  131. Bjornsson E, Olsson R, Bergquist A, et al. The natural history of small-duct primary sclerosing cholangitis. Gastroenterology. 2008;134:975–980
  132. Angulo P, Maor-Kendler Y, Lindor KD. Small-duct primary sclerosing cholangitis: a long-term follow-up study. Hepatology. 2002;35:1494–1500
  133. Boberg KM, Schrumpf E, Fausa O, et al. Hepatobiliary disease in ulcerative colitis. An analysis of 18 patients with hepatobiliary lesions classified as small-duct primary sclerosing cholangitis. Scand J Gastroenterol. 1994;29:744–752
  134. Broome U, Glaumann H, Lindstom E, et al. Natural history and outcome in 32 Swedish patients with small duct primary sclerosing cholangitis (PSC). J Hepatol. 2002;36:586–589
  135. Rabinovitz M, Demetris AJ, Bou-Abboud CF, et al. Simultaneous occurrence of primary sclerosing cholangitis and autoimmune chronic active hepatitis in a patient with ulcerative colitis. Dig Dis Sci. 1992;37:1606–1611
  136. Lawrence SP, Sherman KE, Lawson JM, et al. A 39 year old man with chronic hepatitis. Semin Liver Dis. 1994;14:97–105
  137. Perdigoto R, Carpenter HA, Czaja AJ. Frequency and significance of chronic ulcerative colitis in severe corticosteroid-treated autoimmune hepatitis. J Hepatol. 1992;14:325–331
  138. Floreani A, Rizzotto ER, Ferrara F, et al. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol. 2005;100:1516–1522
  139. Debray D, Pariente D, Urvoas E, et al. Sclerosing cholangitis in children. J Pediatr. 1994;124:49–56
  140. Wilschanski M, Chait P, Wade JA, et al. Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis. Hepatology. 1995;22:1415–1422
  141. Feldstein AE, Perrault J, El-Youssif M, et al. Primary sclerosing cholangitis in children: a long-term follow-up study. Hepatology. 2003;38:210–217
  142. Batres LA, Russo P, Mathews M, et al. Primary sclerosing cholangitis in children: a histologic follow-up study. Pediatr Dev Pathol. 2005;8:568–576
  143. Miloh T, Arnon R, Shneider B, et al. A retrospective single-center review of primary sclerosing cholangitis in children. Clin Gastroenterol Hepatol. 2009;7:239–245
  144. Gregorio GV, Portmann B, Karani J, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology. 2001;33:544–553
  145. McNair AN, Moloney M, Portmann BC, et al. Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases. Am J Gastroenterol. 1998;93:777–784
  146. Boberg KM, Egeland T, Schrumpf E. Long-term effect of corticosteroid treatment in primary sclerosing cholangitis patients. Scand J Gastroenterol. 2003;38:991–995
  147. Rosen CB, Nagorney DM, Wiesner RH, et al. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg. 1991;213:21–25
  148. Bergquist A, Glaumann H, Persson B, et al. Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case–control study. Hepatology. 1998;27:311–316
  149. Chalasani N, Baluyut A, Ismail A, et al. Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case–control study. Hepatology. 2000;31:7–11
  150. Blechacz BR, Sanchez W, Gores GJ. A conceptual proposal for staging ductal cholangiocarcinoma. Curr Opin Gastroenterol. 2009;25:238–239
  151. Khan SA, Davidson BR, Goldin R, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document. Gut. 2002;51:VI1–VI9
  152. Malhi H, Gores GJ. Review article: the modern diagnosis and therapy of cholangiocarcinoma. Aliment Pharmacol Ther. 2006;23:1287–1296
  153. Campbell WL, Ferris JV, Holbert BL, et al. Biliary tract carcinoma complicating primary sclerosing cholangitis: evaluation with CT, cholangiography, US, and MR imaging. Radiology. 1998;207:41–50
  154. Teefey SA, Baron RL, Rohrmann CA, et al. Sclerosing cholangitis: CT findings. Radiology. 1988;169:635–639
  155. Zhang Y, Uchida M, Abe T, et al. Intrahepatic peripheral cholangiocarcinoma: comparison of dynamic CT and dynamic MRI. J Comput Assist Tomogr. 1999;23:670–677
  156. Lee MG, Park KB, Shin YM, et al. Preoperative evaluation of hilar cholangiocarcinoma with contrast-enhanced three-dimensional fast imaging with steady-state precession magnetic resonance angiography: comparison with intraarterial digital subtraction angiography. World J Surg. 2003;27:278–283
  157. Kluge R, Schmidt F, Caca K, et al. Positron emission tomography with [(18)F]fluoro-2-deoxy-d-glucose for diagnosis and staging of bile duct cancer. Hepatology. 2001;33:1029–1035
  158. Prytz H, Keiding S, Bjornsson E, et al. Dynamic FDG-PET is useful for detection of cholangiocarcinoma in patients with PSC listed for liver transplantation. Hepatology. 2006;44:1572–1580
  159. Anderson CD, Rice MH, Pinson CW, et al. Fluorodeoxyglucose PET imaging in the evaluation of gallbladder carcinoma and cholangiocarcinoma. J Gastrointest Surg. 2004;8:90–97
  160. Fevery J, Buchel O, Nevens F, et al. Positron emission tomography is not a reliable method for the early diagnosis of cholangiocarcinoma in patients with primary sclerosing cholangitis. J Hepatol. 2005;43:358–360
  161. Tischendorf JJ, Kruger M, Trautwein C, et al. Cholangioscopic characterization of dominant bile duct stenoses in patients with primary sclerosing cholangitis. Endoscopy. 2006;38:665–669
  162. Tischendorf JJ, Meier PN, Schneider A, et al. Transpapillary intraductal ultrasound in the evaluation of dominant bile duct stenoses in patients with primary sclerosing cholangitis. Scand J Gastroenterol. 2007;42:1011–1017
  163. Charatcharoenwitthaya P, Enders FB, Halling KC, et al. Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis. Hepatology. 2008;48:1106–1117
  164. Moreno Luna LE, Kipp B, Halling KC, et al. Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures. Gastroenterology. 2006;131:1064–1072
  165. Kipp BR, Stadheim LM, Halling SA, et al. A comparison of routine cytology and fluorescence in situ hybridization for the detection of malignant bile duct strictures. Am J Gastroenterol. 2004;99:1675–1681
  166. Baron TH, Harewood GC, Rumalla A, et al. A prospective comparison of digital image analysis and routine cytology for the identification of malignancy in biliary tract strictures. Clin Gastroenterol Hepatol. 2004;2:214–219
  167. Bonney GK, Craven RA, Prasad R, et al. Circulating markers of biliary malignancy: opportunities in proteomics?. Lancet Oncol. 2008;9:149–158
  168. Mullighan CG, Goorha S, Radtke I, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007;446:758–764
  169. Miller G, Socci ND, Dhall D, et al. Genome wide analysis and clinical correlation of chromosomal and transcriptional mutations in cancers of the biliary tract. J Exp Clin Cancer Res. 2009;28:62
  170. Spratlin JL, Serkova NJ, Eckhardt SG. Clinical applications of metabolomics in oncology: a review. Clin Cancer Res. 2009;15:431–440
  171. Alvaro D. Serum and bile biomarkers for cholangiocarcinoma. Curr Opin Gastroenterol. 2009;25:279–284
  172. Alvaro D, Macarri G, Mancino MG, et al. Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis. Ann Intern Med. 2007;147:451–459
  173. Stiehl A, Walker S, Stiehl L, et al. 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;20:57–64
  174. Mitchell SA, Bansi DS, Hunt N, et al. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology. 2001;121:900–907
  175. Beuers U, Spengler U, Kruis W, et al. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial. Hepatology. 1992;16:707–714
  176. Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med. 1997;336:691–695
  177. 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;129:1464–1472
  178. Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50:808–814
  179. Shi J, Li Z, Zeng X, et al. Ursodeoxycholic acid in primary sclerosing cholangitis: meta-analysis of randomized controlled trials. Hepatol Res. 2009;39:865–873
  180. Cullen SN, Rust C, Fleming K, et al. High dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis is safe and effective. J Hepatol. 2008;48:792–800
  181. Harnois DM, Angulo P, Jorgensen RA, et al. High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis. Am J Gastroenterol. 2001;96:1558–1562
  182. Rudolph G, Kloeters-Plachky P, Rost D, et al. The incidence of cholangiocarcinoma in primary sclerosing cholangitis after long-time treatment with ursodeoxycholic acid. Eur J Gastroenterol Hepatol. 2007;19:487–491
  183. Brandsaeter B, Isoniemi H, Broome U, et al. Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy. J Hepatol. 2004;40:815–822
  184. 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;134:89–95
  185. Pardi DS, Loftus EV, Kremers WK, et al. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology. 2003;124:889–893
  186. Sjoqvist U, Tribukait B, Ost A, et al. Ursodeoxycholic acid treatment in IBD-patients with colorectal dysplasia and/or DNA-aneuploidy: a prospective, double-blind, randomized controlled pilot study. Anticancer Res. 2004;24:3121–3127
  187. Cullen SN, Chapman RW. The medical management of primary sclerosing cholangitis. Semin Liver Dis. 2006;26:52–61
  188. Luth S, Kanzler S, Frenzel C, et al. Characteristics and long-term prognosis of the autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. J Clin Gastroenterol; in press.
  189. Ghazale A, Chari ST, Zhang L, et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134:706–715
  190. Church NI, Pereira SP, Deheragoda MG, et al. Autoimmune pancreatitis: clinical and radiological features and objective response to steroid therapy in a UK series. Am J Gastroenterol. 2007;102:2417–2425
  191. Hirano K, Tada M, Isayama H, et al. Long-term prognosis of autoimmune pancreatitis with and without corticosteroid treatment. Gut. 2007;56:1719–1724
  192. Stiehl A, Rudolph G, Kloters-Plachky P, et al. Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment. J Hepatol. 2002;36:151–156
  193. Baluyut AR, Sherman S, Lehman GA, et al. Impact of endoscopic therapy on the survival of patients with primary sclerosing cholangitis. Gastrointest Endosc. 2001;53:308–312
  194. Gluck M, Cantone NR, Brandabur JJ, et al. A twenty-year experience with endoscopic therapy for symptomatic primary sclerosing cholangitis. J Clin Gastroenterol. 2008;42:1032–1039
  195. Kaya M, Petersen BT, Angulo P, et al. Balloon dilation compared to stenting of dominant strictures in primary sclerosing cholangitis. Am J Gastroenterol. 2001;96:1059–1066
  196. Stiehl A. Primary sclerosing cholangitis: the role of endoscopic therapy. Semin Liver Dis. 2006;26:62–68
  197. Ponsioen CY, Lam K, van Milligen de Wit AW, et al. Four years experience with short term stenting in primary sclerosing cholangitis. Am J Gastroenterol. 1999;94:2403–2407
  198. van Milligen de Wit AW, Rauws EA, van Bracht J, et al. Lack of complications following short-term stent therapy for extrahepatic bile duct strictures in primary sclerosing cholangitis. Gastrointest Endosc. 1997;46:344–347
  199. Bjoro K, Brandsaeter B, Foss A, et al. Liver transplantation in primary sclerosing cholangitis. Semin Liver Dis. 2006;26:69–79
  200. Bjoro K, Schrumpf E. Liver transplantation for primary sclerosing cholangitis. J Hepatol. 2004;40:570–577
  201. Uemura T, Ikegami T, Sanchez EQ, et al. Late acute rejection after liver transplantation impacts patient survival. Clin Transplant. 2008;22:316–323
  202. Graziadei IW, Wiesner RH, Marotta PJ, et al. Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis. Hepatology. 1999;30:1121–1127
  203. Neuberger J. Incidence, timing, and risk factors for acute and chronic rejection. Liver Transpl Surg. 1999;5:S30–S36
  204. Narumi S, Roberts JP, Emond JC, et al. Liver transplantation for sclerosing cholangitis. Hepatology. 1995;22:451–457
  205. Shaked A, Colonna JO, Goldstein L, et al. The interrelation between sclerosing cholangitis and ulcerative colitis in patients undergoing liver transplantation. Ann Surg. 1992;215:598–603
  206. Miki C, Harrison JD, Gunson BK, et al. Inflammatory bowel disease in primary sclerosing cholangitis: an analysis of patients undergoing liver transplantation. Br J Surg. 1995;82:1114–1117
  207. Kugelmas M, Spiegelman P, Osgood MJ, et al. Different immunosuppressive regimens and recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl. 2003;9:727–732
  208. Hoffman CEE. Verschluss der Gallenwege durch Verdickung der Wandungen. Arch Pathol Anat Physiol. 1867;49:206–215
  209. Smith MP, Loe RH. Sclerosing cholangitis; review of recent case reports and associated diseases and four new cases. Am J Surg. 1965;110:239–246
  210. Warren KW, Athanassiades S. Monge JI Primary sclerosing cholangitis. A study of forty-two cases. Am J Surg. 1966;111:23–38
  211. McFarlane IG, Wojcicka BM, Tsantoulas DC, et al. Leukocyte migration inhibition in response to biliary antigens in primary biliary cirrhosis, sclerosing cholangitis, and other chronic liver diseases. Gastroenterology. 1979;76:1333–1340
  212. Chapman RW, Arborgh BA, Rhodes JM, et al. Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology. Gut. 1980;21:870–877
  213. Schrumpf E, Elgjo K, Fausa O, et al. Sclerosing cholangitis in ulcerative colitis. Scand J Gastroenterol. 1980;15:689–697
  214. NIH National Institutes of Health Consensus Development Conference Statement: liver transplantation—June 20–23, 1983. Hepatology. 1984;4:107S–1010S
  215. Wee A, Ludwig J, Coffey RJ, et al. Hepatobiliary carcinoma associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hum Pathol. 1985;16:719–726
  216. Wee A, Ludwig J. Pericholangitis in chronic ulcerative colitis: primary sclerosing cholangitis of the small bile ducts?. Ann Intern Med. 1985;102:581–587
  217. Lerut J, Demetris AJ, Stieber AC, et al. Intrahepatic bile duct strictures after human orthotopic liver transplantation. Recurrence of primary sclerosing cholangitis or unusual presentation of allograft rejection?. Transpl Int. 1988;1:127–130
  218. 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;102:1877–1880
  219. Bergquist A, Lindberg G, Saarinen S, et al. Increased prevalence of primary sclerosing cholangitis among first-degree relatives. J Hepatol. 2005;42:252–256
  220. Hov JR, Boberg KM, Karlsen TH. Autoantibodies in primary sclerosing cholangitis. World J Gastroenterol. 2008;14:3781–3791
  221. Ueno Y, Phillips JO, Ludwig J, et al. Development and characterization of a rodent model of immune-mediated cholangitis. Proc Natl Acad Sci USA. 1996;93:216–220
  222. Boberg KM, Fausa O, Haaland T, et al. Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis. Hepatology. 1996;23:1369–1376
  223. Colombo C. Liver disease in cystic fibrosis. Curr Opin Pulm Med. 2007;13:529–536

PII: S1590-8658(10)00015-0

doi: 10.1016/j.dld.2010.01.011

Digestive and Liver Disease
Volume 42, Issue 6 , Pages 390-400 , June 2010