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Update in the Care and Management of Patients with Primary Sclerosing Cholangitis

  • Liver (S Cotler and E Kallwitz, Section Editors)
  • Published:
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Abstract

Purpose of Review

Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease for which specific medical therapy is not available. The goals of treatment are primarily early detection and management of complications. In this review, we discuss novel therapies under evaluation and provide the foundation for surveillance strategies.

Recent Findings

Drugs under investigation include norursodeoxycholic acid, nuclear receptor agonists, anti-fibrotics, antibiotics, and anti-inflammatory drugs. Endoscopic therapy is indicated for symptomatic dominant strictures and in the work-up of malignancies. Recently, the use of stents was associated with an increased rate of complications compared to balloon dilatation; and long-term stenting should be avoided. Malignancies currently account for most of the PSC-related mortality.

Summary

Many drugs are emerging for the treatment of PSC but liver transplantation is the only treatment modality shown to prolong survival. PSC recurrence occurs in up to 35% of transplanted allografts within a median of 5 years. Surveillance for hepatobiliary and colorectal malignancies is indicated.

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Abbreviations

AASLD:

American Association for the Study of Liver Diseases

ACG:

American College of Gastroenterology

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

ATRA:

All-trans-retinoic acid

BA:

Bile acids

EASL:

European Association for the Study of the Liver

ERCP:

Endoscopic retrograde cholangiopancreatography

FISH:

Fluorescence in situ hybridization

FGF:

Fibroblast growth factor

FXR:

Farsenoid X receptor

HLA:

Human leukocyte antigen

IBD:

Inflammatory bowel disease

IgG4:

IgG subclass 4

LOXL2:

Lysyl oxidase homolog 2

MRCP:

Magnetic resonance cholangiopancreatography

MRI:

Magnetic resonance imaging

MRS:

Mayo risk score

norUDCA:

Norursodeoxycholic acid

OCA:

Obeticholic acid

PPAR:

Peroxisome proliferator-activated receptor

PSC:

Primary sclerosing cholangitis

PXR:

Pregnane X receptor

QOL:

Quality-of-life

RCT:

Randomized control trial

UC:

Ulcerative colitis

UCDA:

Ursodeoxycholic acid

VAP1:

Vascular adhesion protein 1

References

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

  1. Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis – a comprehensive review. J Hepatol. 2017;67:1298–323.

    Article  PubMed  Google Scholar 

  2. •• Boonstra K, Weersma RK, van Erpecum KJ, Rauws EA, Spanier BWM, Poen AC, et al. Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis. Hepatology. 2013;58:2045–55. This well-designed population-based study included 590 patients with PSC followed in 44 hospitals in the Netherlands. The authors demonstrated a longer than expected survival time from diagnosis to transplant/death when selection biases were removed. The risk of cholangiocarcinoma was approximately 400 times greater in PSC patients, while the risk of colorectal cancer was increased up to ten times when compared to patients with ulcerative colitis alone.

    Article  PubMed  CAS  Google Scholar 

  3. Trivedi PJ, Adams DH. Mucosal immunity in liver autoimmunity: a comprehensive review. J Autoimmun. 2013;46:97–111.

    Article  PubMed  CAS  Google Scholar 

  4. Sayin SI, Wahlström A, Felin J, Jäntti S, Marschall H-U, Bamberg K, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013;17:225–35.

    Article  PubMed  CAS  Google Scholar 

  5. Trauner M, Meier PJ, Boyer JL. Molecular pathogenesis of cholestasis. N Engl J Med. 1998;339:1217–27.

    Article  PubMed  CAS  Google Scholar 

  6. Loftus EV, 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;54:91–6.

    Article  PubMed  PubMed Central  Google Scholar 

  7. •• Weismüller 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;152:1975–1984.e8. The international PSC study group performed a retrospective outcome analysis of PSC patients in 37 countries including over 7000 patients in an attempt to estimate the risk of disease progression associated with each clinical phenotype. They established that older age at diagnosis, presence of associated UC—versus other IBD subtypes—and male gender are associated with a worse clinical course and disease progression.

    Article  PubMed  Google Scholar 

  8. Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010;51:660–78.

    Article  PubMed  CAS  Google Scholar 

  9. Mendes FD, Jorgensen R, Keach J, Katzmann JA, Smyrk T, Donlinger J, et al. Elevated serum IgG4 concentration in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2006;101:2070–5.

    Article  PubMed  CAS  Google Scholar 

  10. Ghazale A, Chari ST, Zhang L, Smyrk TC, Takahashi N, Levy MJ, et al. Immunoglobulin G4–associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134:706–15.

    Article  PubMed  Google Scholar 

  11. Ohara H, Nakazawa T, Kawa S, Kamisawa T, Shimosegawa T, Uchida K, et al. Establishment of a serum IgG4 cut-off value for the differential diagnosis of IgG4-related sclerosing cholangitis: a Japanese cohort. J Gastroenterol Hepatol. 2013;28:1247–51.

    Article  PubMed  CAS  Google Scholar 

  12. Boonstra K, Culver EL, de Buy Wenniger LM, van Heerde MJ, van Erpecum KJ, Poen AC, et al. Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. Hepatology. 2014;59:1954–63.

    Article  PubMed  CAS  Google Scholar 

  13. 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;40:39–45.

    Article  PubMed  Google Scholar 

  14. Eaton JE, Dzyubak B, Venkatesh SK, Smyrk TC, Gores GJ, Ehman RL, et al. Performance of magnetic resonance elastography in primary sclerosing cholangitis. J Gastroenterol Hepatol. 2016;31:1184–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Corpechot C, Gaouar F, El Naggar A, Kemgang A, Wendum D, Poupon R, et al. Baseline values and changes in liver stiffness measured by transient elastography are associated with severity of fibrosis and outcomes of patients with primary sclerosing cholangitis. Gastroenterology. 2014;146:970–979.e6.

    Article  PubMed  Google Scholar 

  16. Björnsson E, Olsson R, Bergquist A, Lindgren S, Braden B, Chapman RW, et al. The natural history of small-duct primary sclerosing cholangitis. Gastroenterology. 2008;134:975–80.

    Article  PubMed  Google Scholar 

  17. Singal AK, Stanca CM, Clark V, Dixon L, Levy C, Odin JA, et al. Natural history of small duct primary sclerosing cholangitis: a case series with review of the literature. Hepatol Int. 2011;5:808–13.

    Article  PubMed  CAS  Google Scholar 

  18. 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;15:330–40.

    Article  PubMed  Google Scholar 

  19. Graziadei IW, Wiesner RH, Batts KP, Marotta PJ, LaRusso NF, Porayko MK, et al. Recurrence of primary sclerosing cholangitis following liver transplantation. Hepatology. 1999;29:1050–6.

    Article  PubMed  CAS  Google Scholar 

  20. 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;14:138–43.

    Article  PubMed  Google Scholar 

  21. Alexander J, Lord JD, Yeh MM, Cuevas C, Bakthavatsalam R, Kowdley KV. Risk factors for recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl. 2008;14:245–51.

    Article  PubMed  Google Scholar 

  22. 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 (London, England). 2002;360:1943–4.

    Article  Google Scholar 

  23. Beuers U. Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:318–28.

    Article  PubMed  CAS  Google Scholar 

  24. Hofmann AF. Bile acids: trying to understand their chemistry and biology with the hope of helping patients. Hepatology. 2009;49:1403–18.

    Article  PubMed  CAS  Google Scholar 

  25. Imam MH, Sinakos E, Gossard AA, Kowdley KV, Luketic VAC, Edwyn Harrison M, et al. High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis. Aliment Pharmacol Ther. 2011;34:1185–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Eaton JE, Silveira MG, Pardi DS, Sinakos E, Kowdley KV, Luketic VAC, et al. High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Am J Gastroenterol. 2011;106:1638–45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Lindor KD, Kowdley KV, Luketic VAC, Harrison ME, McCashland T, Befeler AS, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50:808–14.

    Article  PubMed  CAS  Google Scholar 

  28. Othman MO, Dunkelberg J, Roy PK. Ursodeoxycholic acid in primary sclerosing cholangitis: a meta-analysis and systematic review. Arab J Gastroenterol. 2012;13:103–10.

    Article  PubMed  CAS  Google Scholar 

  29. Triantos CK, Koukias NM, Nikolopoulou VN, Burroughs AK. Meta-analysis: ursodeoxycholic acid for primary sclerosing cholangitis. Aliment Pharmacol Ther. 2011;34:901–10.

    Article  PubMed  CAS  Google Scholar 

  30. Corpechot C, Abenavoli L, Rabahi N, Chrétien Y, Andréani T, Johanet C, et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology. 2008;48:871–7.

    Article  PubMed  CAS  Google Scholar 

  31. Tischendorf JJW, Hecker H, Krüger M, Manns MP, Meier PN. Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am J Gastroenterol. 2007;102:107–14.

    Article  PubMed  Google Scholar 

  32. Tischendorf J, Krüger M, Trautwein C, Duckstein N, Schneider A, Manns M, et al. Cholangioscopic characterization of dominant bile duct Stenoses in patients with primary sclerosing cholangitis. Endoscopy. 2006;38:665–9.

    Article  PubMed  CAS  Google Scholar 

  33. Razumilava N, Gores GJ, Lindor KD. Cancer surveillance in patients with primary sclerosing cholangitis. Hepatology. 2011;54:1842–52.

    Article  PubMed  Google Scholar 

  34. Siddique A, Kowdley KV. Approach to a patient with elevated serum alkaline phosphatase. Clin Liver Dis. 2012;16:199–229.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Stanich PP, Björnsson E, Gossard AA, Enders F, Jorgensen R, Lindor KD. Alkaline phosphatase normalization is associated with better prognosis in primary sclerosing cholangitis. Dig Liver Dis. 2011;43:309–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Lindström L, Hultcrantz R, Boberg KM, Friis-Liby I, Bergquist A. Association between reduced levels of alkaline phosphatase and survival times of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 2013;11:841–6.

    Article  PubMed  CAS  Google Scholar 

  37. Brandsæter B, Isoniemi H, Broomé U, Olausson M, Bäckman L, Hansen B, et al. Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy. J Hepatol. 2004;40:815–22.

    Article  PubMed  Google Scholar 

  38. Pardi DS, Loftus EV, Kremers WK, Keach J, Lindor KD. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology. 2003;124:889–93.

    Article  PubMed  CAS  Google Scholar 

  39. Tung BY, Emond MJ, Haggitt RC, Bronner MP, Kimmey MB, Kowdley KV, 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.

    Article  PubMed  CAS  Google Scholar 

  40. Wolf JM, Rybicki LA, Lashner BA. The impact of ursodeoxycholic acid on cancer, dysplasia and mortality in ulcerative colitis patients with primary sclerosing cholangitis. Aliment Pharmacol Ther. 2005;22:783–8.

    Article  PubMed  CAS  Google Scholar 

  41. Ashraf I, Choudhary A, Arif M, Matteson ML, Hammad HT, Puli SR, et al. Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis. Indian J Gastroenterol. 2012;31:69–74.

    Article  PubMed  Google Scholar 

  42. Wunsch E, Trottier J, Milkiewicz M, Raszeja-Wyszomirska J, Hirschfield GM, Barbier O, et al. Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis. Hepatology. 2014;60:931–40.

    Article  PubMed  CAS  Google Scholar 

  43. European Association for the Study of the Liver. EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51:237–67.

    Article  Google Scholar 

  44. Lindor KD, Kowdley KV, Harrison ME, American College of Gastroenterology. ACG clinical guideline: primary sclerosing cholangitis. Am J Gastroenterol. 2015;110:646–59. quiz 660

    Article  PubMed  CAS  Google Scholar 

  45. Li Y, Tang R, Leung PSC, Gershwin ME, Ma X. Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases. Autoimmun Rev. 2017;16:885–96.

    Article  PubMed  CAS  Google Scholar 

  46. •• Kummen M, Holm K, Anmarkrud JA, Nygård S, Vesterhus M, Høivik 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. 2017;66:611–9. This innovative study sought to characterize the gut microbiota in patients with PSC versus UC alone versus healthy controls. They prospectively collected 543 stool samples to be submitted for gene sequencing. They found that bacterial diversity is reduced in PSC when compared to healthy controls whereas when compared to UC alone there was a distinct global microbial composition. The investigators found an abundance of the Veillonella genus in patients with PSC, a genus that is possibly associated with progressive fibrotic disorders.

    Article  PubMed  Google Scholar 

  47. Hov J, Karlsen T. The microbiome in primary sclerosing cholangitis: current evidence and potential concepts. Semin Liver Dis. 2017;37:314–31.

    Article  PubMed  Google Scholar 

  48. Tabibian JH, Weeding E, Jorgensen RA, Petz JL, Keach JC, Talwalkar JA, et al. Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis—a pilot study. Aliment Pharmacol Ther. 2013;37:604–12.

    Article  PubMed  CAS  Google Scholar 

  49. Färkkilä M, Karvonen A-L, Nurmi H, Nuutinen H, Taavitsainen M, Pikkarainen P, et al. Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo-controlled trial. Hepatology. 2004;40:1379–86.

    Article  PubMed  CAS  Google Scholar 

  50. Davies YK, Cox KM, Abdullah BA, Safta A, Terry AB, Cox KL. Long-term treatment of primary sclerosing cholangitis in children with oral vancomycin: an immunomodulating antibiotic. J Pediatr Gastroenterol Nutr. 2008;47:61–7.

    Article  PubMed  CAS  Google Scholar 

  51. Silveira MG, Torok NJ, Gossard AA, Keach JC, Jorgensen RA, Petz JL, et al. Minocycline in the treatment of patients with primary sclerosing cholangitis: results of a pilot study. Am J Gastroenterol. 2009;104:83–8.

    Article  PubMed  CAS  Google Scholar 

  52. Allegretti J, Kassam Z, Carrellas M, Timberlaker S, Gerardin Y, Pratt D, Korzenik J. Fecal microbiota transplantation improves microbiome diversity and liver enzyme profile in primary sclerosing cholangitis. In: World Congr. Gastroenterol. ACG2017. Orlando; 2017. p. P1425.

  53. Said K, Glaumann H, Bergquist A. Gallbladder disease in patients with primary sclerosing cholangitis. J Hepatol. 2008;48:598–605.

    Article  PubMed  Google Scholar 

  54. Brandt DJ, MacCarty RL, Charboneau JW, LaRusso NF, Wiesner RH, Ludwig J. Gallbladder disease in patients with primary sclerosing cholangitis. AJR Am J Roentgenol. 1988;150:571–4.

    Article  PubMed  CAS  Google Scholar 

  55. Fickert P, Pollheimer MJ, Silbert D, Moustafa T, Halilbasic E, Krones E, et al. Differential effects of norUDCA and UDCA in obstructive cholestasis in mice. J Hepatol. 2013;58:1201–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Hofmann AF, Zakko SF, Lira M, Clerici C, Hagey LR, Lambert KK, et al. Novel biotransformation and physiological properties of norursodeoxycholic acid in humans. Hepatology. 2005;42:1391–8.

    Article  PubMed  CAS  Google Scholar 

  57. •• Fickert P, Hirschfield GM, Denk G, Marschall HU, Altorjay I, Färkkilä M, et al. norUrsodeoxycholic acid improves cholestasis in primary sclerosing cholangitis. J Hepatol. 2017;67:549–58. This well-designed randomized control trial sought to examine the safety and efficacy of norUDCA in PSC patients. They randomized 161 PSC patients in one of four treatment groups: three doses of norUDCA and placebo. The study showed a dose-dependent reduction in serum ALP levels as well as the secondary endpoints which included ALT, AST, and GGT. They also reported a favorable safety profile which was similar to placebo.

    Article  PubMed  CAS  Google Scholar 

  58. Makishima M, Lu TT, Xie W, Whitfield GK, Domoto H, Evans RM, et al. Vitamin D receptor as an intestinal bile acid sensor. Science. 2002;296:1313–6.

    Article  PubMed  CAS  Google Scholar 

  59. Mudaliar S, Henry RR, Sanyal AJ, Morrow L, Marschall H–U, Kipnes M, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology. 2013;145:574–82.e1.

    Article  PubMed  CAS  Google Scholar 

  60. Pellicciari R, Fiorucci S, Camaioni E, Clerici C, Costantino G, Maloney PR, et al. 6α-ethyl-Chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem. 2002;45:3569–72.

    Article  PubMed  CAS  Google Scholar 

  61. Kowdley K, Bowlus C, Levy C, et al.The AESOP trial: a randomized, double-blind, placebo-controlled, phase 2 study of obeticholic acid in patients with primary sclerosing cholangitis. In: AASLD Liver Meet. Washington D.C.; 2017. p. 276.

  62. Assis DN, Abdelghany O, Cai S-Y, Gossard AA, Eaton JE, Keach JC, et al. Combination therapy of all-trans retinoic acid with ursodeoxycholic acid in patients with primary sclerosing cholangitis. J Clin Gastroenterol. 2017;51:e11–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Luo J, Ko B, Ling L, Rossi S, DePaoli A, Tian H. P1140 NGM282 demonstrates potent antifibrotic activity in a mouse model of severe cholestatic fibrosis. J Hepatol. 2015;62:S779.

    Article  Google Scholar 

  64. Mizuno S, Hirano K, Isayama H, Watanabe T, Yamamoto N, Nakai Y, et al. Prospective study of bezafibrate for the treatment of primary sclerosing cholangitis. J Hepatobiliary Pancreat Sci. 2015;22:766–70.

    Article  PubMed  Google Scholar 

  65. Dejman A, Clark V, Martin P, Levy C. Tu1002 fenofibrate improves alkaline phosphatase in primary sclerosing cholangitis. Gastroenterology. 2013;144:S-1028.

    Article  Google Scholar 

  66. Chazouilleres O, Corpechot C, Gaovar F, Poupon R. Fenofibrate improves liver tests in primary sclerosing cholangitis with incomplete response to ursodeoxycholic acid. In: Hepatology; 2010. p. 52:488A.

  67. Talal AH, Feron-Rigodon M, Madere J, Subramanian GM, Bornstein JD. 1319 simtuzumab, an antifibrotic monoclonal antibody against lysyl oxidase-like 2 (LOXL2) enzyme, appears safe and well tolerated in patients with liver disease of diverse etiology. J Hepatol. 2013;58:S532.

    Article  Google Scholar 

  68. Ikenaga N, Peng Z-W, Vaid KA, Liu SB, Yoshida S, Sverdlov DY, et al. Selective targeting of lysyl oxidase-like 2 (LOXL2) suppresses hepatic fibrosis progression and accelerates its reversal. Gut. 2017;66:1697–708.

    Article  PubMed  Google Scholar 

  69. Muir A, Goodman Z, Levy C, Janssen H, Montano-Loza A, Bowlus C, et al. Efficacy and safety of simtuzumab for the treatment of primary sclerosing cholangitis: results of a phase 2b, dose-ranging, randomized, placebo-controlled trial. J Hepatol. 2017;66:S73.

    Article  Google Scholar 

  70. Arndtz K, Corrigan M, Rowe A, Kirkham A, Barton D, Fox RP, et al. Investigating the safety and activity of the use of BTT1023 (Timolumab), in the treatment of patients with primary sclerosing cholangitis (BUTEO): a single-arm, two-stage, open-label, multi-centre, phase II clinical trial protocol. BMJ Open. 2017;7:e015081.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Christensen B, Micic D, Gibson PR, Yarur A, Bellaguarda E, Corsello P, et al. Vedolizumab in patients with concurrent primary sclerosing cholangitis and inflammatory bowel disease does not improve liver biochemistry but is safe and effective for the bowel disease. Aliment Pharmacol Ther. 2018;47:753–62. https://doi.org/10.1111/apt.14525.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  72. Gluck M, Cantone NR, Brandabur JJ, Patterson DJ, Bredfeldt JE, Kozarek RA. A twenty-year experience with endoscopic therapy for symptomatic primary sclerosing cholangitis. J Clin Gastroenterol. 2008;42:1032–9.

    Article  PubMed  Google Scholar 

  73. van den Hazel SJ, Wolfhagen EH, van Buuren HR, van de Meeberg PC, Van Leeuwen DJ. Prospective risk assessment of endoscopic retrograde cholangiography in patients with primary sclerosing cholangitis. Dutch PSC Study Group Endoscopy. 2000;32:779–82.

    Google Scholar 

  74. •• Aabakken L, Karlsen TH, Albert J, Arvanitakis M, Chazouilleres O, Dumonceau JM, et al. Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline. Endoscopy. 2017;49:588–608. This is a comprehensive systematic review put forth by the European Society of Gastrointestinal Endoscopy (ESGE) and EASL on the guidelines for the role of endoscopy in primary sclerosing cholangitis. The group strongly recommends high-quality evidence evaluation for CCA in patients with worsening cholestasis, weight loss, elevated CA 19-9, and/or dominant strictures particularly with enhancing mass lesions.

    Article  PubMed  Google Scholar 

  75. Nanda A, Brown JM, Berger SH, Lewis MM, Barr Fritcher EG, Gores GJ, et al. Triple modality testing by endoscopic retrograde cholangiopancreatography for the diagnosis of cholangiocarcinoma. Therap Adv Gastroenterol. 2015;8:56–65.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Awadallah NS, Chen YK, Piraka C, Antillon MR, Shah RJ. Is there a role for cholangioscopy in patients with primary sclerosing cholangitis? Am J Gastroenterol. 2006;101:284–91.

    Article  PubMed  Google Scholar 

  77. Stiehl A, Rudolph G, Klöters-Plachky P, Sauer P, Walker S. Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment. J Hepatol. 2002;36:151–6.

    Article  PubMed  Google Scholar 

  78. Gotthardt DN, Rudolph G, Klöters-Plachky P, Kulaksiz H, Stiehl A. Endoscopic dilation of dominant stenoses in primary sclerosing cholangitis: outcome after long-term treatment. Gastrointest Endosc. 2010;71:527–34.

    Article  PubMed  Google Scholar 

  79. 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;53:308–12.

    Article  PubMed  CAS  Google Scholar 

  80. Ponsioen CY, Lam K, van Milligen de Wit AW, Huibregtse K, Tytgat GN. Four years experience with short term stenting in primary sclerosing cholangitis. Am J Gastroenterol. 1999;94:2403–7.

    Article  PubMed  CAS  Google Scholar 

  81. Kaya M, Petersen BT, Angulo P, Baron TH, Andrews JC, Gostout CJ, et al. Balloon dilation compared to stenting of dominant strictures in primary sclerosing cholangitis. Am J Gastroenterol. 2001;96:1059–66.

    Article  PubMed  CAS  Google Scholar 

  82. van Milligen de Wit AW, van Bracht J, Rauws EA, Jones EA, Tytgat GN, Huibregtse K. Endoscopic stent therapy for dominant extrahepatic bile duct strictures in primary sclerosing cholangitis. Gastrointest Endosc. 1996;44:293–9.

    Article  PubMed  Google Scholar 

  83. Ponsioen C, Arnelo U, Bergquist A, et al. Multicenter randomized trial comparing short-term stenting versus balloon dilatation for dominant strictures in primary sclerosing cholangitis. In: EASL. The Netherlands; 2017. p. GS-002.

  84. Barkin JA, Levy C, Souto EO. Endoscopic Management of Primary Sclerosing Cholangitis. Ann Hepatol. 2017;16:842–50.

    Article  PubMed  Google Scholar 

  85. Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Lööf L, Danielsson Å, et al. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol. 2002;36:321–7.

    Article  PubMed  Google Scholar 

  86. Claessen MMH, Vleggaar FP, Tytgat KMAJ, Siersema PD, van Buuren HR. High lifetime risk of cancer in primary sclerosing cholangitis. J Hepatol. 2009;50:158–64.

    Article  PubMed  Google Scholar 

  87. de Valle MB, Björnsson E, Lindkvist B. Mortality and cancer risk related to primary sclerosing cholangitis in a Swedish population-based cohort. Liver Int. 2012;32:441–8.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  89. 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;99:523–6.

    Article  PubMed  Google Scholar 

  90. Culver EL, Chapman RW. Systematic review: management options for primary sclerosing cholangitis and its variant forms—IgG4-associated cholangitis and overlap with autoimmune hepatitis. Aliment Pharmacol Ther. 2011;33:1273–91.

    Article  PubMed  CAS  Google Scholar 

  91. 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;50:1734–40.

    Article  PubMed  CAS  Google Scholar 

  92. Sinakos E, Saenger AK, Keach J, Kim WR, Lindor KD. Many patients with primary sclerosing cholangitis and increased serum levels of carbohydrate antigen 19-9 do not have cholangiocarcinoma. Clin Gastroenterol Hepatol. 2011;9:434–439.e1.

    Article  PubMed  CAS  Google Scholar 

  93. Horsley-Silva JL, Rodriguez EA, Franco DL, Lindor KD. An update on cancer risk and surveillance in primary sclerosing cholangitis. Liver Int. 2017;37:1103–9.

    Article  PubMed  Google Scholar 

  94. Quinn KP, Tabibian JH, Lindor KD. Clinical implications of serial versus isolated biliary fluorescence in situ hybridization (FISH) polysomy in primary sclerosing cholangitis. Scand J Gastroenterol. 2017;52:377–81.

    Article  PubMed  CAS  Google Scholar 

  95. Rosen CB, Heimbach JK, Gores GJ. Surgery for cholangiocarcinoma: the role of liver transplantation. HPB (Oxford). 2008;10:186–9.

    Article  CAS  Google Scholar 

  96. Buckles DC, Lindor KD, Larusso NF, Petrovic LM, Gores GJ. In primary sclerosing cholangitis, gallbladder polyps are frequently malignant. Am J Gastroenterol. 2002;97:1138–42.

    Article  PubMed  Google Scholar 

  97. 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;31:907–13.

    Article  PubMed  Google Scholar 

  98. Eaton JE, Thackeray EW, Lindor KD. Likelihood of malignancy in gallbladder polyps and outcomes following cholecystectomy in primary sclerosing cholangitis. Am J Gastroenterol. 2012;107:431–9.

    Article  PubMed  Google Scholar 

  99. Bruix J, Sherman M, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.

    Article  PubMed  Google Scholar 

  100. Arndtz K, Hirschfield GM. Primary sclerosing cholangitis and the management of uncertainty and complexity. Frontline Gastroenterol. 2017;8:260–6.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Soetikno RM, Lin OS, Heidenreich PA, Young HS, Blackstone MO. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc. 2002;56:48–54.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, University of Miami/Jackson Memorial Hospital, Miami, FL, USA

    Mai Sedki

  2. Division of Hepatology, University of Miami Miller School of Medicine, 1500 NW 12th Avenue, Suite 1101, Miami, FL, USA

    Cynthia Levy

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  1. Mai Sedki
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  2. Cynthia Levy
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Correspondence to Cynthia Levy.

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Conflict of Interest

Cynthia Levy reports grants and personal fees from Intercept Pharmaceuticals, grants from Tobira, grants from Gilead, grants from NGM, grants from Shire (formerly LUMENA), grants from High Tide, grants from DURECT, outside the submitted work.

Mai Sedki declares no conflict of interest.

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

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This article is part of the Topical Collection on Liver

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Sedki, M., Levy, C. Update in the Care and Management of Patients with Primary Sclerosing Cholangitis. Curr Gastroenterol Rep 20, 29 (2018). https://doi.org/10.1007/s11894-018-0635-8

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