Treatment options for primary sclerosing cholangitis

Expert Review of Gastroenterology and Hepatology

Volumn 4, Issue 4, 2010, Pages 473-488

  Sinakos, Emmanouil ^a   Lindor, Keith ^a  

^a MAYO CLINIC   (United States)

Author keywords

cholangiocarcinoma; inflammatory bowel disease; liver transplantation; primary sclerosing cholangitis; ursodeoxycholic acid

Indexed keywords

ANTIFIBROTIC AGENT; AZATHIOPRINE; BILE ACID; CA 19-9 ANTIGEN; CLADRIBINE; COLCHICINE; COLESTYRAMINE; ETANERCEPT; IMMUNOGLOBULIN G4; IMMUNOSUPPRESSIVE AGENT; LACTULOSE; METRONIDAZOLE; NALTREXONE; NICOTINE; PENTOXIFYLLINE; PLACEBO; PREDNISOLONE; RIFAMPICIN; RIFAXIMIN; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; URSODEOXYCHOLIC ACID;

AUTOIMMUNE HEPATITIS; BACTERIAL INFECTION; BILE DUCT CARCINOMA; BILE DUCT OBSTRUCTION; BILIARY TRACT SURGERY; CANCER RISK; CHOLECYSTECTOMY; COLON RESECTION; COLORECTAL CANCER; DISEASE ASSOCIATION; DISEASE CLASSIFICATION; DISEASE COURSE; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG FATALITY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; END STAGE LIVER DISEASE; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; ENDOSCOPIC THERAPY; ENTERITIS; GALLBLADDER DISEASE; HEPATIC ENCEPHALOPATHY; HEPATITIS; HUMAN; LIVER CIRRHOSIS; LIVER FIBROSIS; LIVER TRANSPLANTATION; OSTEODYSTROPHY; PATHOGENESIS; PERCUTANEOUS TRANSHEPATIC CHOLANGIOGRAPHY; PRIMARY SCLEROSING CHOLANGITIS; PRURITUS; RECOMMENDED DRUG DOSE; RECURRENT DISEASE; RECURRENT INFECTION; REVIEW; SURVIVAL TIME; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; VARICOSIS;

BILIARY TRACT SURGICAL PROCEDURES; CHOLAGOGUES AND CHOLERETICS; CHOLANGITIS, SCLEROSING; DILATATION; DISEASE PROGRESSION; ENDOSCOPY, DIGESTIVE SYSTEM; GASTROINTESTINAL AGENTS; HUMANS; LIVER TRANSPLANTATION; TIME FACTORS; TREATMENT OUTCOME; URSODEOXYCHOLIC ACID;

EID: 77955255696     PISSN: 17474124     EISSN: None     Source Type: Journal    
DOI: 10.1586/egh.10.33     Document Type: Review

References (208)

1. Chapman RW, Arborgh BA, Rhodes JM et al. Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology. Gut 21(10), 870-877 (1980).
2. Lee YM, Kaplan MM. Primary sclerosing cholangitis. N. Engl. J. Med. 332(14), 924-933 (1995).
3. Bambha K, Kim WR, Talwalkar J et al. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology 125(5), 1364-1369 (2003).
4. Ang TL, Fock KM, Ng TM, Teo EK, Chua TS, Tan JY. Clinical profle of primary sclerosing cholangitis in Singapore. J. Gastroenterol. Hepatol. 17(8), 908-913 (2002).
5. Escorsell A, Pares A, Rodes J, Solis-Herruzo JA, Miras M, de la Morena E. Epidemiology of primary sclerosing cholangitis in Spain. Spanish Association for the Study of the Liver. J. Hepatol. 21(5), 787-791 (1994).
6. Kingham JG, Kochar N, Gravenor MB. Incidence, clinical patterns, and outcomes of primary sclerosing cholangitis in South Wales, United Kingdom. Gastroenterology 126(7), 1929-1930 (2004).
7. Boberg KM, Aadland E, Jahnsen J, Raknerud N, Stiris M, Bell H. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand. J. Gastroenterol. 33(1), 99-103 (1998).
8. Broome U, Bergquist A. Primary sclerosing cholangitis, infammatory bowel disease, and colon cancer. Semin. Liver Dis. 26(1), 31-41 (2006).
9. LaRusso NF, Shneider BL, Black D et al. Primary sclerosing cholangitis: summary of a workshop. Hepatology 44(3), 746-764 (2006).
10. Schrumpf E, Fausa O, Forre O, Dobloug JH, Ritland S, Thorsby E. HLA antigens and immunoregulatory T cells in ulcerative colitis associated with hepatobiliary disease. Scand. J. Gastroenterol. 17(2), 187-191 (1982). (Pubitemid 12185520)
11. Karlsen TH, Franke A, Melum E et al. Genome-wide association analysis in primary sclerosing cholangitis. Gastroenterology 138(3), 1102-1111 (2010)
12. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J. Hepatol. 51(2), 237-267 (2009).
13. Chapman R Fevery J, Kalloo A et al. Diagnosis and management of primary sclerosing cholangitis (PSC). Hepatology 51(2), 660-678 (2010).
14. Lewin M, Vilgrain V, Ozenne V et al. Prevalence of sclerosing cholangitis in adults with autoimmune hepatitis: a prospective magnetic resonance imaging and histological study. Hepatology 50(2), 528-537 (2009).
15. Burak KW, Angulo P, Lindor KD. Is there a role for liver biopsy in primary sclerosing cholangitis? Am. J. Gastroenterol. 98(5), 1155-1158 (2003).
16. Abdalian R, Heathcote EJ. Sclerosing cholangitis: a focus on secondary causes. Hepatology 44(5), 1063-1074 (2006).
17. Kim WR, Ludwig J, Lindor KD. Variant forms of cholestatic diseases involving small bile ducts in adults. Am. J. Gastroenterol. 95(5), 1130-1138 (2000).
18. Angulo P, Maor-Kendler Y, Lindor KD. Small-duct primary sclerosing cholangitis: a long-term follow-up study. Hepatology 35(6), 1494-1500 (2002).
19. Bjornsson E, Olsson R, Bergquist A et al. The natural history of small-duct primary sclerosing cholangitis. Gastroenterology 134(4), 975-980 (2008).
20. Bjornsson E, Chari ST, Smyrk TC, Lindor K. Immunoglobulin G4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology 45(6), 1547-1554 (2007).
21. Zen Y, Fujii T, Harada K et al. Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology 45(6), 1538-1546 (2007).
22. Ghazale A, Chari ST, Zhang L et al. Immunoglobulin G4-associated cholangitis: clinical profle and response to therapy. Gastroenterology 134(3), 706-715 (2008).
23. Gohlke F, Lohse AW, Dienes HP et al. Evidence for an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis. J. Hepatol. 24(6), 699-705 (1996).
24. Floreani A, Rizzotto ER, Ferrara F et al. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am. J. Gastroenterol. 100(7), 1516-1522 (2005).
25. Gregorio GV, Portmann B, Karani J et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology 33(3), 544-553 (2001).
26. Abdo AA, Bain VG, Kichian K, Lee SS. Evolution of autoimmune hepatitis to primary sclerosing cholangitis: a sequential syndrome. Hepatology 36(6), 1393-1399 (2002).
27. Broome U, Olsson R, Loof L et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 38(4), 610-615 (1996).
28. Farrant JM, Hayllar KM, Wilkinson ML et al. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 100(6), 1710-1717 (1991).
29. Wiesner RH, Grambsch PM, Dickson ER et al. Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis. Hepatology 10(4), 430-436 (1989).
30. 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 38(1), 210-217 (2003).
31. Wilschanski M, Chait P, Wade JA et al. Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis. Hepatology 22(5), 1415-1422 (1995).
32. 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 92(6), 1869-1875 (1987).
33. Ponsioen CY, Vrouenraets SM, Prawirodirdjo W et al. Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population. Gut 51(4), 562-566 (2002).
34. Tischendorf JJ, Hecker H, Kruger M, Manns MP, Meier PN. Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am. J. Gastroenterol. 102(1), 107-114 (2007).
35. Porayko MK, Wiesner RH, LaRusso NF et al. Patients with asymptomatic primary sclerosing cholangitis frequently have progressive disease. Gastroenterology 98(6), 1594-1602 (1990).
36. Bergquist A, Ekbom A, Olsson R et al. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J. Hepatol. 36(3), 321-327 (2002).
37. Kim WR, Therneau TM, Wiesner RH et al. A revised natural history model for primary sclerosing cholangitis. Mayo Clin. Proc. 75(7), 688-694 (2000).
38. Boberg KM, Rocca G, Egeland T et al. Time-dependent Cox regression model is superior in prediction of prognosis in primary sclerosing cholangitis. Hepatology 35(3), 652-657 (2002).
39. Tanaka A, Takamori Y, Toda G, Ohnishi S, Takikawa H. Outcome and prognostic factors of 391 Japanese patients with primary sclerosing cholangitis. Liver Int. 28(7), 983-989 (2008).
40. Aadland E, Schrumpf E, Fausa O et al. Primary sclerosing cholangitis: a long-term follow-up study. Scand. J. Gastroenterol. 22(6), 655-664 (1987). (Pubitemid 17134654)
41. Olsson R, Danielsson A, Jarnerot G et al. Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. Gastroenterology 100(5 Pt 1), 1319-1323 (1991).
42. 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. 32(6), 604-610 (1997).
43. Loftus EV Jr, Harewood GC, Loftus CG et al. PSC-IBD: a unique form of infammatory bowel disease associated with primary sclerosing cholangitis. Gut 54(1), 91-96 (2005).
44. Schrumpf E, Elgjo K, Fausa O, Gjone E, Kolmannskog F, Ritland S. Sclerosing cholangitis in ulcerative colitis. Scand. J. Gastroenterol. 15(6), 689-697 (1980).
45. Verdonk RC, Dijkstra G, Haagsma EB et al. Infammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease. Am. J. Transplant. 6(6), 1422-1429 (2006).
46. O'Mahony CA, Vierling JM. Etiopathogenesis of primary sclerosing cholangitis. Semin. Liver Dis. 26(1), 3-21 (2006).
47. Grant AJ, Lalor PF, Salmi M, Jalkanen S, Adams DH. Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of infammatory bowel disease. Lancet 359(9301), 150-157 (2002).
48. Chapman R, Cullen S. Etiopathogenesis of primary sclerosing cholangitis. World J. Gastroenterol. 14(21), 3350-3359 (2008).
49. Broome U, Lofberg R, Lundqvist K, Veress B. Subclinical time span of infammatory bowel disease in patients with primary sclerosing cholangitis. Dis. Colon Rectum 38(12), 1301-1305 (1995).
50. 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 40(4), 451-456 (1997).
51. Penna C, Dozois R, Tremaine W et al. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut 38(2), 234-239 (1996). (Pubitemid 26046819)
52. Wiesner RH, LaRusso NF, Dozois RR, Beaver SJ. Peristomal varices after proctocolectomy in patients with primary sclerosing cholangitis. Gastroenterology 90(2), 316-322 (1986).
53. Brentnall TA, Haggitt RC, Rabinovitch PS et al. Risk and natural history of colonic neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis. Gastroenterology 110(2), 331-338 (1996).
54. Kornfeld D, Ekbom A, Ihre T. Is there an excess risk for colorectal cancer in patients with ulcerative colitis and concomitant primary sclerosing cholangitis? A population based study. Gut 41(4), 522-525 (1997).
55. Shetty K, Rybicki L, Brzezinski A, Carey WD, Lashner BA. The risk for cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis. Am. J. Gastroenterol. 94(6), 1643-1649 (1999).
56. 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. 56(1), 48-54 (2002).
57. Angulo P, Therneau TM, Jorgensen A et al. Bone disease in patients with primary sclerosing cholangitis: prevalence, severity and prediction of progression. J. Hepatol. 29(5), 729-735 (1998).
58. Campbell MS, Lichtenstein GR, Rhim AD, Pazianas M, Faust T. Severity of liver disease does not predict osteopenia or low bone mineral density in primary sclerosing cholangitis. Liver Int. 25(2), 311-316 (2005).
59. Guichelaar MM, Kendall R, Malinchoc M, Hay JE. Bone mineral density before and after OLT: long-term follow-up and predictive factors. Liver Transpl. 12(9), 1390-1402 (2006).
60. Guichelaar MM, Schmoll J, Malinchoc M, Hay JE. Fractures and avascular necrosis before and after orthotopic liver transplantation: long-term follow-up and predictive factors. Hepatology 46(4), 1198-1207 (2007).
61. Brandt DJ, MacCarty RL, Charboneau JW, LaRusso NF, Wiesner RH, Ludwig J. Gallbladder disease in patients with primary sclerosing cholangitis. AJR Am. J. Roentgenol. 150(3), 571-574 (1988).
62. Said K, Glaumann H, Bergquist A. Gallbladder disease in patients with primary sclerosing cholangitis. J. Hepatol. 48(4), 598-605 (2008).
63. 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. 31(6), 907-913 (2007).
64. Buckles DC, Lindor KD, Larusso NF, Petrovic LM, Gores GJ. In primary sclerosing cholangitis, gallbladder polyps are frequently malignant. Am. J. Gastroenterol. 97(5), 1138-1142 (2002).
65. Treeprasertsuk S, Sinakos E, Keach J, Lindor K. Long-term outcome of gallbladder polyps in patients with primary sclerosing cholangitis. Gastroenterology 138(5), S787 (2010).
66. 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. 99(3), 523-526 (2004).
67. Charatcharoenwitthaya P, Enders FB, Halling KC, Lindor KD. Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis. Hepatology 48(4), 1106-1117 (2008).
68. Claessen MM, Vleggaar FP, Tytgat KM, Siersema PD, van Buuren HR. High lifetime risk of cancer in primary sclerosing cholangitis. J. Hepatol. 50(1), 158-164 (2009).
69. Fevery J, Verslype C, Lai G, Aerts R, Van Steenbergen W. Incidence, diagnosis, and therapy of cholangiocarcinoma in patients with primary sclerosing cholangitis. Dig. Dis. Sci. 52(11), 3123-3135 (2007).
70. Ahrendt SA, Pitt HA, Nakeeb A et al. Diagnosis and management of cholangiocarcinoma in primary sclerosing cholangitis. J. Gastrointest. Surg. 3(4), 357-367; discussion 367-368 (1999).
71. Bjornsson E, Angulo P. Cholangiocarcinoma in young individuals with and without primary sclerosing cholangitis. Am. J. Gastroenterol. 102(8), 1677-1682 (2007).
72. Gores GJ. Early detection and treatment of cholangiocarcinoma. Liver Transpl. 6(6 Suppl. 2), S30-S34 (2000).
73. Rea DJ, Heimbach JK, Rosen CB et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann. Surg. 242(3), 451-458; discussion 458-461 (2005).
74. Levy C, Lymp J, Angulo P, Gores GJ, Larusso N, Lindor KD. The value of serum CA 19-19 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis. Dig. Dis. Sci. 50(9), 1734-1740 (2005).
75. Albert MB Steinberg WM, Henry JP. Elevated serum levels of tumor markers CA 19-19 in acute cholangitis. Dig. Dis. Sci. 33, 1223-1225 (1988).
76. Maestranzi S, Przemioslo R, Mitchell H, Sherwood RA. The effect of benign and malignant liver disease on the tumour markers CA19-9 and CEA. Ann. Clin. Biochem. 35(Pt 1), 99-103 (1998).
77. Murray MD, Burton FR, Di Bisceglie AM. Markedly elevated serum CA 19-19 levels in association with a benign biliary stricture due to primary sclerosing cholangitis. J. Clin. Gastroenterol. 41(1), 115-117 (2007).
78. Boberg KM, Jebsen P, Clausen OP, Foss A, Aabakken L, Schrumpf E. Diagnostic beneft of biliary brush cytology in cholangiocarcinoma in primary sclerosing cholangitis. J. Hepatol. 45(4), 568-574 (2006).
79. Moreno Luna LE, Kipp B, Halling KC et al. Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures. Gastroenterology 131(4), 1064-1072 (2006).
80. Siqueira E, Schoen RE, Silverman W et al. Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis. Gastrointest. Endosc. 56(1), 40-47 (2002).
81. Bangarulingam SY, Bjornsson E, Enders F et al. Long-term outcomes of positive fuorescence in situ hybridization tests in primary sclerosing cholangitis. Hepatology 51(1), 174-180 (2010).
82. 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. 101(2), 284-291 (2006).
83. Shah RJ, Langer DA, Antillon MR, Chen YK. Cholangioscopy and cholangioscopic forceps biopsy in patients with indeterminate pancreaticobiliary pathology. Clin. Gastroenterol. Hepatol. 4(2), 219-225 (2006).
84. Tischendorf JJ, Kruger M, Trautwein C et al. Cholangioscopic characterization of dominant bile duct stenoses in patients with primary sclerosing cholangitis. Endoscopy 38(7), 665-669 (2006).
85. LaRusso NF, Wiesner RH, Ludwig J, MacCarty RL, Beaver SJ, Zinsmeister AR. Prospective trial of penicillamine in primary sclerosing cholangitis. Gastroenterology 95(4), 1036-1042 (1988).
86. Olsson R, Broome U, Danielsson A et al. Colchicine treatment of primary sclerosing cholangitis. Gastroenterology 108(4), 1199-1203 (1995).
87. Angulo P, MacCarty RL, Sylvestre PB et al. Pirfenidone in the treatment of primary sclerosing cholangitis. Dig. Dis. Sci. 47(1), 157-161 (2002). (Pubitemid 34075033)
88. van Milligen de Wit AW, Kuiper H, Camoglio L et al. Does ursodeoxycholic acid mediate immunomodulatory and anti-infammatory effects in patients with primary sclerosing cholangitis? Eur J. Gastroenterol. Hepatol. 11(2), 129-136 (1999).
89. Bharucha AE, Jorgensen R, Lichtman SN, LaRusso NF, Lindor KD. A pilot study of pentoxifylline for the treatment of primary sclerosing cholangitis. Am. J. Gastroenterol. 95(9), 2338-2342 (2000).
90. Epstein MP, Kaplan MM. A pilot study of etanercept in the treatment of primary sclerosing cholangitis. Dig. Dis. Sci. 49(1), 1-4 (2004).
91. Hommes DW, Erkelens W, Ponsioen C et al. A double-blind, placebo-controlled, randomized study of infiximab in primary sclerosing cholangitis. J. Clin. Gastroenterol. 42(5), 522-526 (2008).
92. Angulo P, Batts K P, Jorgensen RA, LaRusso NA, Lindor KD. Oral budesonide in the treatment of primary sclerosing cholangitis. Am. J. Gastroenterol. 95(9), 2333-2337 (2000).
93. Knox TA, Kaplan MM. A double-blind controlled trial of oral-pulse methotrexate therapy in the treatment of primary sclerosing cholangitis. Gastroenterology 106(2), 494-499 (1994).
94. Sandborn WJ, Wiesner RH, Tremaine WJ, Larusso NF. Ulcerative colitis disease activity following treatment of associated primary sclerosing cholangitis with cyclosporin. Gut 34(2), 242-246 (1993).
95. Sterling RK, Salvatori JJ, Luketic VA et al. A prospective, randomized-controlled pilot study of ursodeoxycholic acid combined with mycophenolate mofetil in the treatment of primary sclerosing cholangitis. Aliment. Pharmacol. Ther. 20(9), 943-949 (2004).
96. Talwalkar JA, Angulo P, Keach JC, Petz JL, Jorgensen RA, Lindor KD. Mycophenolate mofetil for the treatment of primary sclerosing cholangitis. Am. J. Gastroenterol. 100(2), 308-312 (2005). (Pubitemid 40314514)
97. Talwalkar JA, Gossard AA, Keach JC, Jorgensen RA, Petz JL, Lindor RN. Tacrolimus for the treatment of primary sclerosing cholangitis. Liver Int. 27(4), 451-453 (2007).
98. Van Thiel DH, Carroll P, Abu-Elmagd K et al. Tacrolimus (FK 506), a treatment for primary sclerosing cholangitis: results of an open-label preliminary trial. Am. J. Gastroenterol. 90(3), 455-459 (1995).
99. Lindor KD, Jorgensen RA, Anderson ML, Gores GJ, Hofmann AF, LaRusso NF. Ursodeoxycholic acid and methotrexate for primary sclerosing cholangitis: a pilot study. Am. J. Gastroenterol. 91(3), 511-515 (1996).
100. Lindor KD, Wiesner RH, Colwell LJ, Steiner B, Beaver S, LaRusso NF. The combination of prednisone and colchicine in patients with primary sclerosing cholangitis. Am. J. Gastroenterol. 86(1), 57-61 (1991).
101. Schramm C, Schirmacher P, Helmreich-Becker I, Gerken G, zum Buschenfelde KH, Lohse AW. Combined therapy with azathioprine, prednisolone, and ursodiol in patients with primary sclerosing cholangitis. A case series. Ann. Intern. Med. 131(12), 943-946 (1999).
102. van Hoogstraten HJ, Vleggaar FP, Boland GJ et al. Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double-blind pilot study. Belgian-Dutch PSC Study Group. Am. J. Gastroenterol. 95(8), 2015-2022 (2000).
103. Elfaki DA, Lindor KD. Antibiotics for the treatment of primary sclerosing cholangitis. Am. J. Ther. DOI: 10.1097/MJT. 0b013e3181b7b8c0 (2009) (Epub ahead of print).
104. Farkkila M, Karvonen AL, Nurmi H et al. Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo-controlled trial. Hepatology 40(6), 1379-1386 (2004).
105. 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. 47(1), 61-67 (2008).
106. Silveira MG, Torok NJ, Gossard AA et al. Minocycline in the treatment of patients with primary sclerosing cholangitis: results of a pilot study. Am. J. Gastroenterol. 104(1), 83-88 (2009).
107. Lazaridis KN, Gores GJ, Lindor KD. Ursodeoxycholic acid 'mechanisms of action and clinical use in hepatobiliary disorders'. J. Hepatol. 35(1), 134-146 (2001).
108. Beuers U, Spengler U, Kruis W et al. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial. Hepatology 16(3), 707-714 (1992).
109. Stiehl A, Walker S, Stiehl L, Rudolph G, Hofmann WJ, Theilmann L. Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period. J. Hepatol. 20(1), 57-64 (1994).
110. Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N. Engl. J. Med. 336(10), 691-695 (1997).
111. 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. 48(5), 792-800 (2008).
112. Harnois DM, Angulo P, Jorgensen RA, Larusso NF, Lindor KD. High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis. Am. J. Gastroenterol. 96(5), 1558-1562 (2001).
113. Mitchell SA, Bansi DS, Hunt N et al. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology 121(4), 900-907 (2001).
114. 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 129(5), 1464-1472 (2005).
115. Lindor KD, Kowdley K V, Luketic VA et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 50(3), 808-814 (2009).
116. Angulo P, Bharucha AE, Jorgensen RA et al. Oral nicotine in treatment of primary sclerosing cholangitis: a pilot study. Dig. Dis. Sci. 44(3), 602-607 (1999).
117. Vleggaar FP, van Buuren HR, van Berge Henegouwen GP, Hop WC, van Erpecum KJ. No benefcial effects of transdermal nicotine in patients with primary sclerosing cholangitis: results of a randomized double-blind placebo-controlled cross-over study. Eur J. Gastroenterol. Hepatol. 13(2), 171-175 (2001).
118. Duchini A, Younossi ZM, Saven A, Bordin GM, Knowles HJ, Pockros PJ. An open-label pilot trial of cladibrine (2-cholordeoxyadenosine) in patients with primary sclerosing cholangitis. J. Clin. Gastroenterol. 31(4), 292-296 (2000).
119. Angulo P, Jorgensen RA, Kowdley KV, Lindor KD. Silymarin in the treatment of patients with primary sclerosing cholangitis: an open-label pilot study. Dig. Dis. Sci. 53(6), 1716-1720 (2008).
120. Vleggaar FP, Monkelbaan JF, van Erpecum KJ. Probiotics in primary sclerosing cholangitis: a randomized placebo-controlled crossover pilot study. Eur J. Gastroenterol. Hepatol. 20(7), 688-692 (2008).
121. Stiehl A, Rudolph G, Kloters-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. 36(2), 151-156 (2002).
122. Okolicsanyi L, Fabris L, Viaggi S, Carulli N, Podda M, Ricci G. Primary sclerosing cholangitis: clinical presentation, natural history and prognostic variables: an Italian multicentre study. The Italian PSC Study Group. Eur J. Gastroenterol. Hepatol. 8(7), 685-691 (1996).
123. Campbell WL, Peterson MS, Federle MP et al. Using CT and cholangiography to diagnose biliary tract carcinoma complicating primary sclerosing cholangitis. AJR Am. J. Roentgenol. 177(5), 1095-1100 (2001).
124. Lindberg B, Arnelo U, Bergquist A et al. Diagnosis of biliary strictures in conjunction with endoscopic retrograde cholangiopancreaticography, with special reference to patients with primary sclerosing cholangitis. Endoscopy 34(11), 909-916 (2002).
125. Rudolph G, Gotthardt D, Kloters-Plachky P, Kulaksiz H, Rost D, Stiehl A. Infuence of dominant bile duct stenoses and biliary infections on outcome in primary sclerosing cholangitis. J. Hepatol. 51(1), 149-155 (2009).
126. Hammel P, Couvelard A, O'Toole D et al. Regression of liver fbrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N. Engl. J. Med. 344(6), 418-423 (2001).
127. Stiehl A. Primary sclerosing cholangitis: the role of endoscopic therapy. Semin. Liver Dis. 26(1), 62-68 (2006). (Pubitemid 43320728)
128. 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. 53(3), 308-312 (2001).
129. 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. 42(9), 1032-1039 (2008).
130. Johnson GK, Saeian K, Geenen JE. Primary sclerosing cholangitis treated by endoscopic biliary dilation: review and long-term follow-up evaluation. Curr. Gastroenterol. Rep. 8(2), 147-155 (2006).
131. Ahrendt SA, Pitt HA, Kalloo AN et al. Primary sclerosing cholangitis: resect, dilate, or transplant? Ann. Surg. 227(3), 412-423 (1998).
132. Gaing AA, Geders JM, Cohen SA, Siegel JH. Endoscopic management of primary sclerosing cholangitis: review, and report of an open series. Am. J. Gastroenterol. 88(12), 2000-2008 (1993).
133. Kaya M, Petersen BT, Angulo P et al. Balloon dilation compared to stenting of dominant strictures in primary sclerosing cholangitis. Am. J. Gastroenterol. 96(4), 1059-1066 (2001).
134. 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. 94(9), 2403-2407 (1999).
135. 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 32(10), 779-782 (2000).
136. Pohl J, Ring A, Stremmel W, Stiehl A. The role of dominant stenoses in bacterial infections of bile ducts in primary sclerosing cholangitis. Eur J. Gastroenterol. Hepatol. 18(1), 69-74 (2006).
137. Cameron JL, Pitt HA, Zinner MJ et al. Resection of hepatic duct bifurcation and transhepatic stenting for sclerosing cholangitis. Ann. Surg. 207(5), 614-622 (1988).
138. Pawlik TM, Olbrecht VA, Pitt HA et al. Primary sclerosing cholangitis: role of extrahepatic biliary resection. J. Am. Coll. Surg. 206(5), 822-830; discussion 830-832 (2008).
139. Myburgh JA. Surgical biliary drainage in primary sclerosing cholangitis. The role of the Hepp-Couinaud approach. Arch. Surg. 129(10), 1057-1062 (1994).
140. Brandsaeter B, Broome U, Isoniemi H et al. Liver transplantation for primary sclerosing cholangitis in the Nordic countries: outcome after acceptance to the waiting list. Liver Transpl. 9(9), 961-969 (2003). (Pubitemid 37098845)
141. Welsh FK, Wigmore SJ. Roux-en-Y choledochojejunostomy is the method of choice for biliary reconstruction in liver transplantation for primary sclerosing cholangitis. Transplantation 77(4), 602-604 (2004).
142. Bjoro K, Brandsaeter B, Foss A, Schrumpf E. Liver transplantation in primary sclerosing cholangitis. Semin. Liver Dis. 26(1), 69-79 (2006).
143. Mathis KL, Dozois EJ, Larson DW et al. Ileal pouch-anal anastomosis and liver transplantation for ulcerative colitis complicated by primary sclerosing cholangitis. Br. J. Surg. 95(7), 882-886 (2008).
144. Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 69(8), 1633-1637 (2000).
145. Brandsaeter B, Friman S, Broome U et al. Outcome following liver transplantation for primary sclerosing cholangitis in the Nordic countries. Scand. J. Gastroenterol. 38(11), 1176-1183 (2003).
146. Graziadei I W, Wiesner RH, Marotta PJ et al. Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis. Hepatology 30(5), 1121-1127 (1999).
147. Roberts MS, Angus DC, Bryce CL, Valenta Z, Weissfeld L. Survival after liver transplantation in the United States: a disease-specifc analysis of the UNOS database. Liver Transpl. 10(7), 886-897 (2004).
148. Egawa H, Taira K, Teramukai S et al. Risk factors for recurrence of primary sclerosing cholangitis after living donor liver transplantation: a single center experience. Dig. Dis. Sci. 54(6), 1347-1354 (2009).
149. Kashyap R, Mantry P, Sharma R et al. Comparative analysis of outcomes in living and deceased donor liver transplants for primary sclerosing cholangitis. J. Gastrointest. Surg. 13(8), 1480-1486 (2009).
150. Tamura S, Sugawara Y, Kaneko J, Matsui Y, Togashi J, Makuuchi M. Recurrence of primary sclerosing cholangitis after living donor liver transplantation. Liver Int. 27(1), 86-94 (2007). (Pubitemid 46139432)
151. Seaberg EC, Belle SH, Beringer KC, Schivins JL, Detre KM. Liver transplantation in the United States from 1987-1998: updated results from the Pitt-UNOS Liver Transplant Registry. Clin. Transpl. 17-37 (1998).
152. Dvorchik I, Subotin M, Demetris AJ et al. Effect of liver transplantation on infammatory bowel disease in patients with primary sclerosing cholangitis. Hepatology 35(2), 380-384 (2002).
153. Papatheodoridis GV, Hamilton M, Mistry PK, Davidson B, Rolles K, Burroughs AK. Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis. Gut 43(5), 639-644 (1998).
154. Haagsma EB, Van Den Berg AP, Kleibeuker JH, Slooff MJ, Dijkstra G. Infammatory bowel disease after liver transplantation: the effect of different immunosuppressive regimens. Aliment. Pharmacol. Ther. 18(1), 33-44 (2003).
155. Loftus EV Jr, Aguilar HI, Sandborn WJ et al. Risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis following orthotopic liver transplantation. Hepatology 27(3), 685-690 (1998).
156. Vera A, Gunson BK, Ussatoff V et al. Colorectal cancer in patients with infammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Transplantation 75(12), 1983-1988 (2003).
157. Graziadei IW, Wiesner RH, Batts KP et al. Recurrence of primary sclerosing cholangitis following liver transplantation. Hepatology 29(4), 1050-1056 (1999).
158. Gautam M, Cheruvattath R, Balan V. Recurrence of autoimmune liver disease after liver transplantation: a systematic review. Liver Transpl. 12(12), 1813-1824 (2006).
159. Alexander J, Lord JD, Yeh MM, Cuevas C, Bakthavatsalam R, Kowdley K V. Risk factors for recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl. 14(2), 245-251 (2008).
160. Brandsaeter B, Schrumpf E, Bentdal O et al. Recurrent primary sclerosing cholangitis after liver transplantation: a magnetic resonance cholangiography study with analyses of predictive factors. Liver Transpl. 11(11), 1361-1369 (2005).
161. Campsen J, Zimmerman MA, Trotter JF et al. Clinically recurrent primary sclerosing cholangitis following liver transplantation: a time course. Liver Transpl. 14(2), 181-185 (2008).
162. Cholongitas E, Shusang V, Papatheodoridis GV et al. Risk factors for recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl. 14(2), 138-143 (2008).
163. Kugelmas M, Spiegelman P, Osgood MJ et al. Different immunosuppressive regimens and recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl. 9(7), 727-732 (2003).
164. Charatcharoenwitthaya P, Lindor KD. Recurrence of primary sclerosing cholangitis: what do we learn from several transplant centers? Liver Transpl. 14(2), 130-132 (2008).
165. Alabraba E, Nightingale P, Gunson B et al. A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts. Liver Transpl. 15(3), 330-340 (2009).
166. Rowe IA, Webb K, Gunson BK, Mehta N, Haque S, Neuberger J. The impact of disease recurrence on graft survival following liver transplantation: a single centre experience. Transpl. Int. 21(5), 459-465 (2008).
167. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa N V, Heathcote EJ. Primary biliary cirrhosis. Hepatology 50(1), 291-308 (2009).
168. Bergasa NV, Alling DW, Talbot TL et al. Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial. Ann. Intern. Med. 123(3), 161-167 (1995).
169. Tabibian N. Rifampin as antipruritic agent in primary sclerosing cholangitis. Am. J. Gastroenterol. 84(3), 340 (1989).
170. Tandon P, Rowe BH, Vandermeer B, Bain VG. The effcacy and safety of bile acid binding agents, opioid antagonists, or rifampin in the treatment of cholestasis-associated pruritus. Am. J. Gastroenterol. 102(7), 1528-1536 (2007).
171. Wolfhagen FH, Sternieri E, Hop WC, Vitale G, Bertolotti M, Van Buuren HR. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology 113(4), 1264-1269 (1997).
172. Mayo MJ, Handem I, Saldana S, Jacobe H, Getachew Y, Rush AJ. Sertraline as a frst-line treatment for cholestatic pruritus. Hepatology 45(3), 666-674 (2007).
173. Bellmann R, Graziadei IW, Feistritzer C et al. Treatment of refractory cholestatic pruritus after liver transplantation with albumin dialysis. Liver Transpl. 10(1), 107-114 (2004).
174. Pares A, Cisneros L, Salmeron JM et al. Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis. Am. J. Gastroenterol. 99(6), 1105-1110 (2004).
175. Bangarulingam SY, Gossard AA, Petersen BT, Ott BJ, Lindor KD. Complications of endoscopic retrograde cholangiopancreatography in primary sclerosing cholangitis. Am. J. Gastroenterol. 104(4), 855-860 (2009).
176. Bjornsson ES, Kilander AF, Olsson RG. Bile duct bacterial isolates in primary sclerosing cholangitis and certain other forms of cholestasis-a study of bile cultures from ERCP. Hepatogastroenterology 47(36), 1504-1508 (2000).
177. Bajaj JS. Review article: the modern management of hepatic encephalopathy. Aliment. Pharmacol. Ther. 31(5), 537-547 (2010).
178. Gorgun E, Remzi FH, Manilich E, Preen M, Shen B, Fazio V W. Surgical outcome in patients with primary sclerosing cholangitis undergoing ileal pouch-anal anastomosis: a case-control study. Surgery 138(4), 631-637; discussion 637-639 (2005).
179. Kartheuser AH, Dozois RR, LaRusso NF, Wiesner RH, Ilstrup DM, Schleck CD. Comparison of surgical treatment of ulcerative colitis associated with primary sclerosing cholangitis: ileal pouch-anal anastomosis versus Brooke ileostomy. Mayo Clin. Proc. 71(8), 748-756 (1996).
180. Poritz LS, Koltun WA. Surgical management of ulcerative colitis in the presence of primary sclerosing cholangitis. Dis. Colon Rectum 46(2), 173-178 (2003).
181. Itzkowitz SH, Present DH. Consensus conference: colorectal cancer screening and surveillance in infammatory bowel disease. Infamm. Bowel Dis. 11(3), 314-321 (2005).
182. Martinez JD, Stratagoules ED, LaRue JM et al. Different bile acids exhibit distinct biological effects: the tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation. Nutr. Cancer 31(2), 111-118 (1998).
183. 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. 134(2), 89-95 (2001).
184. 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. 22(9), 783-788 (2005).
185. Pardi DS, Loftus EV Jr, Kremers WK, Keach J, Lindor KD. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology 124(4), 889-893 (2003).
186. Collier J. Bone disorders in chronic liver disease. Hepatology 46(4), 1271-1278 (2007).
187. Zein CO, Jorgensen RA, Clarke B et al. Alendronate improves bone mineral density in primary biliary cirrhosis: a randomized placebo-controlled trial. Hepatology 42(4), 762-771 (2005).
188. Kaya M, de Groen PC, Angulo P et al. Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience. Am. J. Gastroenterol. 96(4), 1164-1169 (2001).
189. Brandsaeter B, Isoniemi H, Broome U et al. Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy. J. Hepatol. 40(5), 815-822 (2004).
190. Rudolph G, Kloeters-Plachky P, Rost D, Stiehl A. The incidence of cholangiocarcinoma in primary sclerosing cholangitis after long-time treatment with ursodeoxycholic acid. Eur J. Gastroenterol. Hepatol. 19(6), 487-491 (2007).
191. Iwatsuki S, Todo S, Marsh JW et al. Treatment of hilar cholangiocarcinoma (Klatskin tumors) with hepatic resection or transplantation. J. Am. Coll. Surg. 187(4), 358-364 (1998).
192. Rosen CB, Nagorney DM, Wiesner RH, Coffey RJ Jr, LaRusso NF. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann. Surg. 213(1), 21-25 (1991).
193. Ghali P, Marotta PJ, Yoshida EM et al. Liver transplantation for incidental cholangiocarcinoma: analysis of the Canadian experience. Liver Transpl. 11(11), 1412-1416 (2005).
194. Sudan D, DeRoover A, Chinnakotla S et al. Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am. J. Transplant. 2(8), 774-779 (2002).
195. Lindor KD, Lacerda MA, Jorgensen RA et al. Relationship between biliary and serum bile acids and response to ursodeoxycholic acid in patients with primary biliary cirrhosis. Am. J. Gastroenterol. 93(9), 1498-1504 (1998).
196. Lubel JS, Herath CB, Burrell LM, Angus PW. Liver disease and the renin-angiotensin system: recent discoveries and clinical implications. J. Gastroenterol. Hepatol. 23(9), 1327-1338 (2008).
197. Zhu J, Wu J, Frizell E et al. Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fbrogenesis in an in vivo model of liver fbrosis. Gastroenterology 117(5), 1198-1204 (1999).
198. Biecker E, De Gottardi A, Neef M et al. Long-term treatment of bile duct-ligated rats with rapamycin (sirolimus) signifcantly attenuates liver fbrosis: analysis of the underlying mechanisms. J. Pharmacol. Exp. Ther. 313(3), 952-961 (2005).
199. Bridle KR, Popa C, Morgan ML et al. Rapamycin inhibits hepatic fbrosis in rats by attenuating multiple profbrogenic pathways. Liver Transpl. 15(10), 1315-1324 (2009).
200. Neef M, Ledermann M, Saegesser H, Schneider V, Reichen J. Low-dose oral rapamycin treatment reduces fbrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis. J. Hepatol. 45(6), 786-796 (2006).
201. -/- mice. Hepatology 49(6), 1972-1981 (2009).
202. Hofmann AF, Zakko SF, Lira M et al. Novel biotransformation and physiological properties of norursodeoxycholic acid in humans. Hepatology 42(6), 1391-1398 (2005).
203. Beuers U, Kullak-Ublick GA, Pusl T, Rauws ER, Rust C. Medical treatment of primary sclerosing cholangitis: a role for novel bile acids and other (post-) transcriptional modulators? Clin. Rev. Allergy Immunol. 36(1), 52-61 (2009).
204. Pellicciari R, Fiorucci S, Camaioni E et al. 6a-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J. Med. Chem. 45(17), 3569-3572 (2002).
205. Fiorucci S, Antonelli E, Rizzo G et al. The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fbrosis. Gastroenterology 127(5), 1497-1512 (2004).
206. Fiorucci S, Clerici C, Antonelli E et al. Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. J. Pharmacol. Exp. Ther. 313(2), 604-612 (2005).
207. -/- mice. J. Pediatr. Gastroenterol. Nutr. 42(3), 275-281 (2006).
208. Chapman RW. High-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis: throwing the urso out with the bathwater? Hepatology 50(3), 671-673 (2009).