Skip to main content

Advertisement

Log in

The IBD and PSC Phenotypes of PSC-IBD

  • Pediatric Gastroenterology (S Orenstein, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Purpose of review

To review the characteristics of IBD and PSC that occur in association, as well as their reciprocal influences on disease evolution, in adult and pediatric populations.

Recent findings

IBD co-existing with PSC is genetically and clinically distinct from IBD alone. It is frequently characterized by pancolitis, rectal sparing, and possibly backwash ileitis, as well as a threefold increased risk of colorectal dysplasia. Adults and children with colitis and PSC appear to be at increased risk of active endoscopic and histologic disease in the absence of symptoms compared to individuals without PSC. PSC occurring with Crohn’s disease has been observed to be less severe than PSC co-existing with ulcerative colitis, independent of its association with small duct disease. Recent studies suggest that colectomy is associated with a decreased risk of recurrent PSC after liver transplantation, challenging the traditional teaching that PSC and IBD evolve independently.

Summary

While much about the gut-liver axis in PSC-IBD remains poorly understood, the IBD associated with PSC has a unique phenotype, of which subclinical inflammation is an important component. Additional research is needed to characterize further the potentially protective role of colectomy against recurrent PSC post-liver transplantation and to investigate the influence of IBD control and/or colectomy on PSC progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis—a comprehensive review. J Hepatol. 2017;67(6):1298–323. https://doi.org/10.1016/j.jhep.2017.07.022.

    Article  PubMed  Google Scholar 

  2. Saffioti F, Gurusamy KS, Hawkins N, Toon CD, Tsochatzis E, Davidson BR, et al. Pharmacological interventions for primary sclerosing cholangitis: an attempted network meta-analysis. Cochrane Database Syst Rev. 2017;3:Cd011343. https://doi.org/10.1002/14651858.CD011343.pub2.

    PubMed  Google Scholar 

  3. Peng X, Luo X, Hou JY, Wu SY, Li LZ, Zheng MH, et al. Immunosuppressive agents for the treatment of primary sclerosing cholangitis: a systematic review and meta-analysis. Dig Dis (Basel, Switzerland). 2017;35(5):478–85. https://doi.org/10.1159/000471874.

    Article  Google Scholar 

  4. Lazaridis KN, LaRusso NF. Primary sclerosing cholangitis. N Engl J Med. 2016;375(12):1161–70. https://doi.org/10.1056/NEJMra1506330.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Weersma RK, Lindor KD. Shifting paradigms: what is the true prevalence and clinical course of primary sclerosing cholangitis? Gastroenterology. 2016;151(4):590–3. https://doi.org/10.1053/j.gastro.2016.08.046.

    Article  PubMed  Google Scholar 

  6. Warren KW, Athanassiades S, Monge JI. Primary sclerosing cholangitis. A study of forty-two cases. Am J Surg. 1966;111(1):23–38.

    Article  CAS  PubMed  Google Scholar 

  7. Karlsen TH. Primary sclerosing cholangitis: 50 years of a gut-liver relationship and still no love? Gut. 2016;65(10):1579–81. https://doi.org/10.1136/gutjnl-2016-312137.

    Article  PubMed  Google Scholar 

  8. Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol. 2012;56(5):1181–8. https://doi.org/10.1016/j.jhep.2011.10.025.

    Article  PubMed  Google Scholar 

  9. •• de Vries AB, Janse M, Blokzijl H, Weersma RK. Distinctive inflammatory bowel disease phenotype in primary sclerosing cholangitis. World J Gastroenterol: WJG. 2015;21(6):1956–71. https://doi.org/10.3748/wjg.v21.i6.1956. Systematic review of studies investigating the IBD phenotype of PSC-IBD in adults.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tanaka A, Takikawa H. Geoepidemiology of primary sclerosing cholangitis: a critical review. J Autoimmun. 2013;46:35–40. https://doi.org/10.1016/j.jaut.2013.07.005.

    Article  CAS  PubMed  Google Scholar 

  11. Palmela C, Peerani F, Castaneda D, Torres J, Itzkowitz SH. Inflammatory bowel disease and primary sclerosing cholangitis: a review of the phenotype and associated specific features. Gut Liver. 2017 https://doi.org/10.5009/gnl16510.

  12. Olsson R, Danielsson A, Jarnerot G, Lindstrom E, Loof L, Rolny P, et al. Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. Gastroenterology. 1991;100(5 Pt 1):1319–23.

    Article  CAS  PubMed  Google Scholar 

  13. Fraga M, Fournier N, Safroneeva E, Pittet V, Godat S, Straumann A, et al. Primary sclerosing cholangitis in the Swiss inflammatory bowel disease cohort study: prevalence, risk factors, and long-term follow-up. Eur J Gastroenterol Hepatol. 2017;29(1):91–7. https://doi.org/10.1097/meg.0000000000000747.

    Article  PubMed  Google Scholar 

  14. • Lunder AK, Hov JR, Borthne A, Gleditsch J, Johannesen G, Tveit K, et al. Prevalence of sclerosing cholangitis detected by magnetic resonance cholangiography in patients with long-term inflammatory bowel disease. Gastroenterology. 2016;151(4):660–9.e4. https://doi.org/10.1053/j.gastro.2016.06.021. Recent study in which MRCP screening of IBD patients revealed a higher than previously appreciated prevalence of PSC.

    Article  PubMed  Google Scholar 

  15. Boonstra K, Weersma RK, van Erpecum KJ, Rauws EA, Spanier BW, Poen AC, et al. Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis. Hepatology (Baltimore, Md). 2013;58(6):2045–55. https://doi.org/10.1002/hep.26565.

    Article  CAS  Google Scholar 

  16. Fosby B, Karlsen TH, Recurrence ME. Rejection in liver transplantation for primary sclerosing cholangitis. World J Gastroenterol: WJG. 2012;18(1):1–15. https://doi.org/10.3748/wjg.v18.i1.1.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Liu K, Strasser SI, Koorey DJ, Leong RW, Solomon M, McCaughan GW. Interactions between primary sclerosing cholangitis and inflammatory bowel disease: implications in the adult liver transplant setting. Expert Rev Gastroenterol Hepatol. 2017;11(10):949–60. https://doi.org/10.1080/17474124.2017.1343666.

    Article  CAS  PubMed  Google Scholar 

  18. Boberg KM, Bergquist A, Mitchell S, Pares A, Rosina F, Broome U, et al. Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation. Scand J Gastroenterol. 2002;37(10):1205–11.

    Article  CAS  PubMed  Google Scholar 

  19. •• Weismuller TJ, Trivedi PJ, Bergquist A, Imam M, Lenzen H, Ponsioen CY, et al. Patient age, sex, and inflammatory bowel disease phenotype associate with course of primary sclerosing cholangitis. Gastroenterology. 2017; https://doi.org/10.1053/j.gastro.2017.02.038. The largest clinical PSC study to date (>7000 patients). PSC-CD and no IBD were associated with better PSC outcomes than PSC-UC when analyzing IBD as a time-dependent covariate.

  20. Bjornsson E, Boberg KM, Cullen S, Fleming K, Clausen OP, Fausa O, et al. Patients with small duct primary sclerosing cholangitis have a favourable long term prognosis. Gut. 2002;51(5):731–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bjornsson E. Small-duct primary sclerosing cholangitis. Curr Gastroenterol Rep. 2009;11(1):37–41.

    Article  PubMed  Google Scholar 

  22. • Deneau M, Jensen MK, Holmen J, Williams MS, Book LS, Guthery SL. Primary sclerosing cholangitis, autoimmune hepatitis, and overlap in Utah children: epidemiology and natural history. Hepatology (Baltimore, Md). 2013;58(4):1392–400. https://doi.org/10.1002/hep.26454. The largest clinical pediatric PSC study to date, providing natural history data on >700 children.

    Article  Google Scholar 

  23. 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. https://doi.org/10.1111/j.1572-0241.2007.01103.x.

    Article  PubMed  Google Scholar 

  24. Deneau MR, El-Matary W, Valentino PL, Abdou R, Alqoaer K, Amin M, et al. The natural history of primary sclerosing cholangitis in 781 children: a multicenter, international collaboration. Hepatology (Baltimore, Md). 2017; https://doi.org/10.1002/hep.29204.

  25. Eaton JE, McCauley BM, Atkinson EJ, Juran BD, Schlicht EM, de Andrade M, et al. Variations in primary sclerosing cholangitis across the age spectrum. J Gastroenterol Hepatol. 2017;32(10):1763–8. https://doi.org/10.1111/jgh.13774.

    Article  PubMed  Google Scholar 

  26. • Bramuzzo M, Martelossi S, Torre G, Cardile S, Arrigo S, Vignola S, et al. Clinical features and risk factors of autoimmune liver involvement in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2016;63(2):259–64. https://doi.org/10.1097/mpg.0000000000001078. The largest study to date describing the IBD phenotype of PSC-IBD in children.

    Article  CAS  PubMed  Google Scholar 

  27. Yoon J, Oh SH, Kim HJ, Park SH, Ye BD, Yang SK, et al. Primary sclerosing cholangitis with inflammatory bowel disease in Korean children. Pediatr Gastroenterol Hepatol Nutr. 2015;18(4):268–75. https://doi.org/10.5223/pghn.2015.18.4.268.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Feldstein AE, Perrault J, El-Youssif M, Lindor KD, Freese DK, Angulo P. Primary sclerosing cholangitis in children: a long-term follow-up study. Hepatology (Baltimore, Md). 2003;38(1):210–7. https://doi.org/10.1053/jhep.2003.50289.

    Article  Google Scholar 

  29. Miloh T, Arnon R, Shneider B, Suchy F, Kerkar NA. Retrospective single-center review of primary sclerosing cholangitis in children. Clin Gastroenterol Hepatol. 2009;7(2):239–45. https://doi.org/10.1016/j.cgh.2008.10.019.

    Article  PubMed  Google Scholar 

  30. Bazerbachi F, Furuya KN, Abdou R, Alqoaer K, Amin M, Amir A, et al. PS-138—recurrence of primary sclerosing cholangitis after liver transplantation in children: data from the Pediatric PSC Consortium. J Hepatol. 2017;66(1, Supplement):S76. https://doi.org/10.1016/S0168-8278(17)30414-2.

    Article  Google Scholar 

  31. Jiang X, Karlsen TH. Genetics of primary sclerosing cholangitis and pathophysiological implications. Nat Rev Gastroenterol Hepatol. 2017;14:279–95. https://doi.org/10.1038/nrgastro.2016.154.

    Article  CAS  PubMed  Google Scholar 

  32. Ellinghaus D, Folseraas T, Holm K, Ellinghaus E, Melum E, Balschun T, et al. Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4. Hepatology (Baltimore, Md). 2013;58(3):1074–83. https://doi.org/10.1002/hep.25977.

    Article  CAS  Google Scholar 

  33. Janse M, Lamberts LE, Franke L, Raychaudhuri S, Ellinghaus E, Muri Boberg K, et al. Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9. Hepatology (Baltimore, Md). 2011;53(6):1977–85. https://doi.org/10.1002/hep.24307.

    Article  CAS  Google Scholar 

  34. Folseraas T, Melum E, Rausch P, Juran BD, Ellinghaus E, Shiryaev A, et al. Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. J Hepatol. 2012;57(2):366–75. https://doi.org/10.1016/j.jhep.2012.03.031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Eksteen B, Grant AJ, Miles A, Curbishley SM, Lalor PF, Hubscher SG, 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. https://doi.org/10.1084/jem.20041035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Grant AJ, Lalor PF, Salmi M, Jalkanen S, Adams DH. Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease. Lancet. 2002;359(9301):150–7. https://doi.org/10.1016/s0140-6736(02)07374-9.

    Article  PubMed  Google Scholar 

  37. • Ji SG, Juran BD, Mucha S, Folseraas T, Jostins L, Melum E, et al. Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease. Nat Genet. 2017;49(2):269–73. https://doi.org/10.1038/ng.3745. A genome-wide association study of PSC that showed relatively little genetic overlap between PSC and IBD.

    Article  CAS  PubMed  Google Scholar 

  38. O'Hara SP, Karlsen TH, LaRusso NF. Cholangiocytes and the environment in primary sclerosing cholangitis: where is the link? Gut. 2017;66(11):1873–7. https://doi.org/10.1136/gutjnl-2017-314249.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Lichtman SN, Wang J, Clark RL. A microcholangiographic study of liver disease models in rats. Acad Radiol. 1995;2(6):515–21.

    Article  CAS  PubMed  Google Scholar 

  40. Lichtman SN, Sartor RB, Keku J, Schwab JH. Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth. Gastroenterology. 1990;98(2):414–23.

    Article  CAS  PubMed  Google Scholar 

  41. Mueller T, Beutler C, Pico AH, Shibolet O, Pratt DS, Pascher A, et al. Enhanced innate immune responsiveness and intolerance to intestinal endotoxins in human biliary epithelial cells contributes to chronic cholangitis. Liver Int. 2011;31(10):1574–88. https://doi.org/10.1111/j.1478-3231.2011.02635.x.

    Article  CAS  PubMed  Google Scholar 

  42. Tabibian JH, O'Hara SP, Trussoni CE, Tietz PS, Splinter PL, Mounajjed T, et al. Absence of the intestinal microbiota exacerbates hepatobiliary disease in a murine model of primary sclerosing cholangitis. Hepatology (Baltimore, Md). 2016;63(1):185–96. https://doi.org/10.1002/hep.27927.

    Article  CAS  Google Scholar 

  43. Schrumpf E, Jiang X, Zeissig S, Pollheimer MJ, Anmarkrud JA, Tan C, et al. The role of natural killer T cells in a mouse model with spontaneous bile duct inflammation. Phys Rep. 2017;5(4):e13117. https://doi.org/10.14814/phy2.13117.

    Article  Google Scholar 

  44. Torres J, Bao X, Goel A, Colombel JF, Pekow J, Jabri B, et al. The features of mucosa-associated microbiota in primary sclerosing cholangitis. Aliment Pharmacol Ther. 2016;43(7):790–801. https://doi.org/10.1111/apt.13552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kummen M, Holm K, Anmarkrud JA, Nygard S, Vesterhus M, Hoivik ML, et al. The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls. Gut. 2016;66:611–9. https://doi.org/10.1136/gutjnl-2015-310500.

    Article  PubMed  Google Scholar 

  46. Sabino J, Vieira-Silva S, Machiels K, Joossens M, Falony G, Ballet V, et al. Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD. Gut. 2016;65(10):1681–9. https://doi.org/10.1136/gutjnl-2015-311004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Rossen NG, Fuentes S, Boonstra K, D'Haens GR, Heilig HG, Zoetendal EG, et al. The mucosa-associated microbiota of PSC patients is characterized by low diversity and low abundance of uncultured Clostridiales II. J Crohns Colitis. 2015;9(4):342–8. https://doi.org/10.1093/ecco-jcc/jju023.

    Article  PubMed  Google Scholar 

  48. Quraishi MN, Sergeant M, Kay G, Iqbal T, Chan J, Constantinidou C, et al. The gut-adherent microbiota of PSC-IBD is distinct to that of IBD. Gut. 2017;66(2):386–8. https://doi.org/10.1136/gutjnl-2016-311915.

    Article  PubMed  Google Scholar 

  49. Kevans D, Tyler AD, Holm K, Jorgensen KK, Vatn MH, Karlsen TH, et al. Characterization of intestinal microbiota in ulcerative colitis patients with and without primary sclerosing cholangitis. J Crohns Colitis. 2016;10(3):330–7. https://doi.org/10.1093/ecco-jcc/jjv204.

    Article  CAS  PubMed  Google Scholar 

  50. Ruhlemann MC, Heinsen FA, Zenouzi R, Lieb W, Franke A, Schramm C. Faecal microbiota profiles as diagnostic biomarkers in primary sclerosing cholangitis. Gut. 2017;66(4):753–4. https://doi.org/10.1136/gutjnl-2016-312180.

    Article  PubMed  Google Scholar 

  51. Bajer L, Kverka M, Kostovcik M, Macinga P, Dvorak J, Stehlikova Z, et al. Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis. World J Gastroenterol: WJG. 2017;23(25):4548–58. https://doi.org/10.3748/wjg.v23.i25.4548.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology (Baltimore, Md). 2009;50(3):808–14. https://doi.org/10.1002/hep.23082.

    Article  CAS  Google Scholar 

  53. Cangemi JR, Wiesner RH, Beaver SJ, Ludwig J, MacCarty RL, Dozois RR, et al. Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis. Gastroenterology. 1989;96(3):790–4.

    Article  CAS  PubMed  Google Scholar 

  54. Broome U, Lofberg R, Lundqvist K, Veress B. Subclinical time span of inflammatory bowel disease in patients with primary sclerosing cholangitis. Dis Colon Rectum. 1995;38(12):1301–5.

    Article  CAS  PubMed  Google Scholar 

  55. Lundqvist K, Broome U. Differences in colonic disease activity in patients with ulcerative colitis with and without primary sclerosing cholangitis: a case control study. Dis Colon Rectum. 1997;40(4):451–6.

    Article  CAS  PubMed  Google Scholar 

  56. Moayyeri A, Daryani NE, Bahrami H, Haghpanah B, Nayyer-Habibi A, Sadatsafavi M. Clinical course of ulcerative colitis in patients with and without primary sclerosing cholangitis. J Gastroenterol Hepatol. 2005;20(3):366–70.

    Article  PubMed  Google Scholar 

  57. Loftus EV Jr, Harewood GC, Loftus CG, Tremaine WJ, Harmsen WS, Zinsmeister AR, et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut. 2005;54(1):91–6. https://doi.org/10.1136/gut.2004.046615.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Sokol H, Cosnes J, Chazouilleres O, Beaugerie L, Tiret E, Poupon R, et al. Disease activity and cancer risk in inflammatory bowel disease associated with primary sclerosing cholangitis. World J Gastroenterol: WJG. 2008;14(22):3497–503.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Joo M, Abreu-e-Lima P, Farraye F, Smith T, Swaroop P, Gardner L, et al. Pathologic features of ulcerative colitis in patients with primary sclerosing cholangitis: a case-control study. Am J Surg Pathol. 2009;33(6):854–62. https://doi.org/10.1097/PAS.0b013e318196d018.

    Article  PubMed  Google Scholar 

  60. Sano H, Nakazawa T, Ando T, Hayashi K, Naitoh I, Okumura F, et al. Clinical characteristics of inflammatory bowel disease associated with primary sclerosing cholangitis. J Hepatobiliary Pancreat Sci. 2011;18(2):154–61. https://doi.org/10.1007/s00534-010-0319-8.

    Article  PubMed  Google Scholar 

  61. Ye BD, Yang SK, Boo SJ, Cho YK, Yang DH, Yoon SM, et al. Clinical characteristics of ulcerative colitis associated with primary sclerosing cholangitis in Korea. Inflamm Bowel Dis. 2011;17(9):1901–6. https://doi.org/10.1002/ibd.21569.

    Article  PubMed  Google Scholar 

  62. Halliday JS, Djordjevic J, Lust M, Culver EL, Braden B, Travis SP, et al. A unique clinical phenotype of primary sclerosing cholangitis associated with Crohn’s disease. J Crohns Colitis. 2012;6(2):174–81. https://doi.org/10.1016/j.crohns.2011.07.015.

    Article  CAS  PubMed  Google Scholar 

  63. Jorgensen KK, Grzyb K, Lundin KE, Clausen OP, Aamodt G, Schrumpf E, et al. Inflammatory bowel disease in patients with primary sclerosing cholangitis: clinical characterization in liver transplanted and nontransplanted patients. Inflamm Bowel Dis. 2012;18(3):536–45. https://doi.org/10.1002/ibd.21699.

    Article  PubMed  Google Scholar 

  64. O'Toole A, Alakkari A, Keegan D, Doherty G, Mulcahy H, O'Donoghue D. Primary sclerosing cholangitis and disease distribution in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2012;10(4):439–41. https://doi.org/10.1016/j.cgh.2011.11.010.

    Article  PubMed  Google Scholar 

  65. Boonstra K, van Erpecum KJ, van Nieuwkerk KM, Drenth JP, Poen AC, Witteman BJ, et al. Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(12):2270–6. https://doi.org/10.1002/ibd.22938.

    Article  PubMed  Google Scholar 

  66. Schaeffer DF, Win LL, Hafezi-Bakhtiari S, Cino M, Hirschfield GM, El-Zimaity H. The phenotypic expression of inflammatory bowel disease in patients with primary sclerosing cholangitis differs in the distribution of colitis. Dig Dis Sci. 2013;58(9):2608–14. https://doi.org/10.1007/s10620-013-2697-7.

    Article  CAS  PubMed  Google Scholar 

  67. Sinakos E, Samuel S, Enders F, Loftus EV Jr, Sandborn WJ, Lindor KD. Inflammatory bowel disease in primary sclerosing cholangitis: a robust yet changing relationship. Inflamm Bowel Dis. 2013;19(5):1004–9. https://doi.org/10.1097/MIB.0b013e3182802893.

    Article  PubMed  Google Scholar 

  68. Sorensen JO, Nielsen OH, Andersson M, Ainsworth MA, Ytting H, Belard E, et al. Inflammatory bowel disease with primary sclerosing cholangitis: a Danish population-based cohort study 1977-2011. Liver Int. 2017; https://doi.org/10.1111/liv.13548.

  69. • Cleveland NK, Rubin DT, Hart J, Weber CR, Meckel K, Tran AL, et al. Patients with ulcerative colitis and primary sclerosing cholangitis frequently have subclinical inflammation in the proximal colon. Clin Gastroenterol Hepatol. 2017; https://doi.org/10.1016/j.cgh.2017.07.023. Found that adult UC patients in clinical remission with PSC were more likely than those without PSC to have ongoing endoscopic and histologic disease in the right colon.

  70. Feurer ME, Hilden K, Adler DG. Primary sclerosing cholangitis and distribution of inflammatory bowel disease. Clin Gastroenterol Hepatol. 2012;10(12):1418; author reply −9. https://doi.org/10.1016/j.cgh.2012.07.008.

    Article  PubMed  Google Scholar 

  71. 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.

    Article  CAS  PubMed  Google Scholar 

  72. Yanai H, Matalon S, Rosenblatt A, Awadie H, Berdichevski T, Snir Y, et al. Prognosis of primary sclerosing cholangitis in israel is independent of coexisting inflammatory bowel disease. J Crohns Colitis. 2015;9(2):177–84. https://doi.org/10.1093/ecco-jcc/jju013.

    Article  PubMed  Google Scholar 

  73. • Zheng HH, Jiang XL. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies. Eur J Gastroenterol Hepatol. 2016;28(4):383–90. https://doi.org/10.1097/meg.0000000000000576. This large meta-analysis demonstrated that PSC-UC patients have a threefold higher risk of colorectal dysplasia and cancer than UC patients without PSC.

    CAS  PubMed  Google Scholar 

  74. O'Toole A, Walsh P, Keegan D, Byrne K, Doherty G, O'Donoghue D, et al. Mortality in inflammatory bowel disease patients under 65 years of age. Scand J Gastroenterol. 2014;49(7):814–9. https://doi.org/10.3109/00365521.2014.907824.

    Article  PubMed  Google Scholar 

  75. Faubion WA Jr, Loftus EV, Sandborn WJ, Freese DK, Perrault J. Pediatric “PSC-IBD”: a descriptive report of associated inflammatory bowel disease among pediatric patients with psc. J Pediatr Gastroenterol Nutr. 2001;33(3):296–300.

    Article  PubMed  Google Scholar 

  76. Ordonez F, Lacaille F, Canioni D, Talbotec C, Fournet JC, Cerf-Bensussan N, et al. Pediatric ulcerative colitis associated with autoimmune diseases: a distinct form of inflammatory bowel disease? Inflamm Bowel Dis. 2012;18(10):1809–17. https://doi.org/10.1002/ibd.22864.

    Article  PubMed  Google Scholar 

  77. Lascurain L, Jensen MK, Guthery SL, Holmen J, Deneau M. Inflammatory bowel disease phenotype in pediatric primary sclerosing cholangitis. Inflamm Bowel Dis. 2016;22(1):146–50. https://doi.org/10.1097/MIB.0000000000000586.

    Article  PubMed  Google Scholar 

  78. Shiau H, Ihekweazu FD, Amin M, Fofanova T, Miloh T, Kellermayer R. Unique inflammatory bowel disease phenotype of pediatric primary sclerosing cholangitis: a single-center study. J Pediatr Gastroenterol Nutr. 2017;65(4):404–9. https://doi.org/10.1097/mpg.0000000000001531.

    Article  PubMed  Google Scholar 

  79. Torres J, Pineton de Chambrun G, Itzkowitz S, Sachar DB, Colombel JF. Review article: colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease. Aliment Pharmacol Ther. 2011;34(5):497–508. https://doi.org/10.1111/j.1365-2036.2011.04753.x.

    Article  CAS  PubMed  Google Scholar 

  80. Bernstein H, Bernstein C, Payne CM, Dvorakova K, Garewal H. Bile acids as carcinogens in human gastrointestinal cancers. Mutat Res. 2005;589(1):47–65. https://doi.org/10.1016/j.mrrev.2004.08.001.

    Article  CAS  PubMed  Google Scholar 

  81. Torres J, Bao X, Iuga AC, Chen A, Harpaz N, Ullman T, et al. Farnesoid X receptor expression is decreased in colonic mucosa of patients with primary sclerosing cholangitis and colitis-associated neoplasia. Inflamm Bowel Dis. 2013;19(2):275–82. https://doi.org/10.1097/MIB.0b013e318286ff2e.

    Article  PubMed  Google Scholar 

  82. Rubin DT, Huo D, Kinnucan JA, Sedrak MS, McCullom NE, Bunnag AP, et al. Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study. Clin Gastroenterol Hepatol. 2013;11(12):1601–8.e1–4. https://doi.org/10.1016/j.cgh.2013.06.023.

    Article  PubMed  Google Scholar 

  83. Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126(2):451–9.

    Article  PubMed  Google Scholar 

  84. • Ricciuto A, Carman N, Fish J, Crowley E, Church PC, Muise A, et al. 234 symptoms underestimate endoscopic activity in PSC-IBD. J Pediatr Gastroenterol Nutr. 2017;65(supplement 2):S104. Found that children with colitis in clinical remission with PSC are more likely than children without PSC to have ongoing endoscopic and histologic inflammation throughout the colon.

    Google Scholar 

  85. Jorgensen KK, Lindstrom L, Cvancarova M, Karlsen TH, Castedal M, Friman S, et al. Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11(5):517–23. https://doi.org/10.1016/j.cgh.2012.12.027.

    Article  PubMed  Google Scholar 

  86. Fattahi MR, Malek-Hosseini SA, Sivandzadeh GR, Safarpour AR, Bagheri Lankarani K, Taghavi AR, et al. Clinical course of ulcerative colitis after liver transplantation in patients with concomitant primary sclerosing cholangitis and ulcerative colitis. Inflamm Bowel Dis. 2017;23(7):1160–7. https://doi.org/10.1097/mib.0000000000001105.

    Article  PubMed  Google Scholar 

  87. Singh S, Loftus EV Jr, Talwalkar JA. Inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Am J Gastroenterol. 2013;108(9):1417–25. https://doi.org/10.1038/ajg.2013.163.

    Article  CAS  PubMed  Google Scholar 

  88. Dvorchik I, Subotin M, Demetris AJ, Fung JJ, Starzl TE, Wieand S, et al. Effect of liver transplantation on inflammatory bowel disease in patients with primary sclerosing cholangitis. Hepatology (Baltimore, Md). 2002;35(2):380–4. https://doi.org/10.1053/jhep.2002.30695.

    Article  Google Scholar 

  89. Jorgensen KK, Lindstrom L, Cvancarova M, Castedal M, Friman S, Schrumpf E, et al. Colorectal neoplasia in patients with primary sclerosing cholangitis undergoing liver transplantation: a Nordic multicenter study. Scand J Gastroenterol. 2012;47(8–9):1021–9. https://doi.org/10.3109/00365521.2012.685754.

    Article  CAS  PubMed  Google Scholar 

  90. Verdonk RC, Dijkstra G, Haagsma EB, Shostrom VK, Van den Berg AP, Kleibeuker JH, et al. Inflammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2006;6(6):1422–9. https://doi.org/10.1111/j.1600-6143.2006.01333.x.

    Article  CAS  Google Scholar 

  91. Navaneethan U, Choudhary M, Venkatesh PG, Lashner BA, Remzi FH, Shen B, et al. The effects of liver transplantation on the clinical course of colitis in ulcerative colitis patients with primary sclerosing cholangitis. Aliment Pharmacol Ther. 2012;35(9):1054–63. https://doi.org/10.1111/j.1365-2036.2012.05067.x.

    CAS  PubMed  Google Scholar 

  92. Haagsma EB, Van Den Berg AP, Kleibeuker JH, Slooff MJ, Dijkstra G. Inflammatory bowel disease after liver transplantation: the effect of different immunosuppressive regimens. Aliment Pharmacol Ther. 2003;18(1):33–44.

    Article  CAS  PubMed  Google Scholar 

  93. Joshi D, Bjarnason I, Belgaumkar A, O'Grady J, Suddle A, Heneghan MA, et al. The impact of inflammatory bowel disease post-liver transplantation for primary sclerosing cholangitis. Liver Int. 2013;33(1):53–61. https://doi.org/10.1111/j.1478-3231.2011.02677.x.

    Article  PubMed  Google Scholar 

  94. Navaneethan U, Venkatesh PG, Lashner BA, Shen B, Kiran RP. The impact of ulcerative colitis on the long-term outcome of patients with primary sclerosing cholangitis. Aliment Pharmacol Ther. 2012;35(9):1045–53. https://doi.org/10.1111/j.1365-2036.2012.05063.x.

    CAS  PubMed  Google Scholar 

  95. Ricciuto A, Kamath BM, Abdou R, Alqoaer K, Amin M, Amir AZ, et al. 423—a comparison of primary sclerosing cholangitis with and without associated inflammatory bowel disease: data from the Pediatric PSC Consortium. Gastroenterology. 2017;152(5, Supplement 1):S1057. https://doi.org/10.1016/S0016-5085(17)33571-0.

    Article  Google Scholar 

  96. Franceschet I, Cazzagon N, Del Ross T, D'Inca R, Buja A, Floreani A. Primary sclerosing cholangitis associated with inflammatory bowel disease: an observational study in a Southern Europe population focusing on new therapeutic options. Eur J Gastroenterol Hepatol. 2016;28(5):508–13. https://doi.org/10.1097/meg.0000000000000596.

    Article  CAS  PubMed  Google Scholar 

  97. • Fevery J, Van Steenbergen W, Van Pelt J, Laleman W, Hoffman I, Geboes K, et al. Patients with large-duct primary sclerosing cholangitis and Crohn’s disease have a better outcome than those with ulcerative colitis, or without IBD. Aliment Pharmacol Ther. 2016;43(5):612–20. https://doi.org/10.1111/apt.13516. Demonstrated that the improved PSC outcomes in PSC-CD are independent of its association with small duct disease.

    Article  CAS  PubMed  Google Scholar 

  98. Ngu JH, Gearry RB, Wright AJ, Stedman CA. Inflammatory bowel disease is associated with poor outcomes of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 2011;9(12):1092–7; quiz e135. https://doi.org/10.1016/j.cgh.2011.08.027.

    Article  PubMed  Google Scholar 

  99. Martin EF, Levy C. Timing, management, and outcomes of liver transplantation in primary sclerosing cholangitis. Semin Liver Dis. 2017;37(4):305–13. https://doi.org/10.1055/s-0037-1608655.

    Article  PubMed  Google Scholar 

  100. •• Lindstrom L, Jorgensen KK, Boberg KM, Castedal M, Rasmussen A, Rostved AA, et al. Risk factors and prognosis for recurrent primary sclerosing cholangitis after liver transplantation: a Nordic multicentre study. Scand J Gastroenterol. 2018:1–8. https://doi.org/10.1080/00365521.2017.1421705. Observed a significantly decreased risk of recurrent PSC after liver transplantation with colectomy pre- or peri-transplant.

  101. •• Ravikumar R, Tsochatzis E, Jose S, Allison M, Athale A, Creamer F, et al. Risk factors for recurrent primary sclerosing cholangitis after liver transplantation. J Hepatol. 2015; https://doi.org/10.1016/j.jhep.2015.07.005. Found ulcerative colitis post-liver transplant (vs no UC or colectomy before transplant) to be a risk factor for recurrent PSC after transplantation.

  102. Alabraba E, Nightingale P, Gunson B, Hubscher S, Olliff S, Mirza D, et al. A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts. Liver Transpl. 2009;15(3):330–40. https://doi.org/10.1002/lt.21679.

    Article  PubMed  Google Scholar 

  103. Vera A, Moledina S, Gunson B, Hubscher S, Mirza D, Olliff S, et al. Risk factors for recurrence of primary sclerosing cholangitis of liver allograft. Lancet. 2002;360(9349):1943–4. https://doi.org/10.1016/s0140-6736(02)11861-7.

    Article  PubMed  Google Scholar 

  104. Cholongitas E, Shusang V, Papatheodoridis GV, Marelli L, Manousou P, Rolando N, et al. Risk factors for recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl. 2008;14(2):138–43. https://doi.org/10.1002/lt.21260.

    Article  PubMed  Google Scholar 

  105. Nordenvall C, Olén O, Nilsson PJ, von Seth E, Ekbom A, Bottai M et al. Colectomy prior to diagnosis of primary sclerosing cholangitis is associated with improved prognosis in a nationwide cohort study of 2594 PSC-IBD patients. Aliment. Pharmacol. Ther. 2018;47(2):238–45. https://doi.org/10.1111/apt.14393.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amanda Ricciuto.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Pediatric Gastroenterology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ricciuto, A., Kamath, B.M. & Griffiths, A.M. The IBD and PSC Phenotypes of PSC-IBD. Curr Gastroenterol Rep 20, 16 (2018). https://doi.org/10.1007/s11894-018-0620-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11894-018-0620-2

Keywords

Navigation