Primary Sclerosing Cholangitis: Epidemiology, Natural History, and Prognosis

Cynthia Levy; Keith D. Lindor

doi:10.1055/s-2006-933560

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2006; 26(1): 022-030
DOI: 10.1055/s-2006-933560

Primary Sclerosing Cholangitis: Epidemiology, Natural History, and Prognosis

Cynthia Levy¹ , Keith D. Lindor²

¹Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Health Sciences Building, Gainesville, Florida
²Mayo Medical School, Division of Gastroenterology and Hepatology, Mayo Foundation, Rochester, Minnesota

Abstract

ABSTRACT

Primary sclerosing cholangitis is a progressive disease associated with significant morbidity and mortality that continues to draw attention from investigators worldwide. Epidemiologic studies indicate that its annual incidence remains stable, although more asymptomatic cases are being diagnosed. Nevertheless, even asymptomatic cases can progress to end-stage liver disease, albeit at a highly variable rate. Moreover, patients are predisposed to several malignancies, especially cholangiocarcinoma, which contributes to their decreased survival. On the other hand, a subgroup of patients with the so-called small-duct variant may have a better prognosis, and those with overlap syndromes with autoimmune hepatitis may respond well to immunosuppressants. Otherwise, efficient treatment is not available for patients with primary sclerosing cholangitis. Thus, even though it occurs rarely, this disease is commonly an indication for liver transplantation. Fortunately, transplantation outcomes are excellent, with overall 5-year survival rates of approximately 80%.

KEYWORDS

Primary sclerosing cholangitis - epidemiology - natural history - liver transplantation

Full Text

References

REFERENCES

1 Lee Y M, Kaplan M M. Primary sclerosing cholangitis. N Engl J Med. 1995; 332(14) 924-933
2 Aoki C A, Bowlus C L, Gershwin M E. The immunobiology of primary sclerosing cholangitis. Autoimmun Rev. 2005; 4(3) 137-143
3 Broome U, Olsson R, Loof L et al.. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996; 38(4) 610-615
4 Bambha K, Kim W R, Talwalkar J et al.. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology. 2003; 125(5) 1364-1369
5 Escorsell A, Pares A, Rodes J et al.. Epidemiology of primary sclerosing cholangitis in Spain. Spanish Association for the Study of the Liver. J Hepatol. 1994; 21(5) 787-791
6 Okolicsanyi L, Fabris L, Viaggi S et al.. Primary sclerosing cholangitis: clinical presentation, natural history and prognostic variables: an Italian multicentre study. The Italian PSC Study Group. Eur J Gastroenterol Hepatol. 1996; 8(7) 685-691
7 Wiesner R H, Grambsch P M, Dickson E R et al.. Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis. Hepatology. 1989; 10(4) 430-436
8 Graziadei I W, Wiesner R H, Marotta P J et al.. Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis. Hepatology. 1999; 30(5) 1121-1127
9 Boberg K M, Aadland E, Jahnsen J et al.. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol. 1998; 33(1) 99-103
10 Schrumpf E, Elgjo K, Fausa O et al.. Sclerosing cholangitis in ulcerative colitis. Scand J Gastroenterol. 1980; 15(6) 689-697
11 Shepherd H A, Selby W S, Chapman R W et al.. Ulcerative colitis and persistent liver dysfunction. Q J Med. 1983; 52(208) 503-513
12 Tobias R, Wright J P, Kottler R E et al.. Primary sclerosing cholangitis associated with inflammatory bowel disease in Cape Town, 1975-1981. S Afr Med J. 1983; 63(7) 229-235
13 Olsson R, Danielsson A, Jarnerot G et al.. Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. Gastroenterology. 1991; 100(5 Pt 1) 1319-1323
14 Broome U, Glaumann H, Hellers G et al.. Liver disease in ulcerative colitis: an epidemiological and follow up study in the county of Stockholm. Gut. 1994; 35(1) 84-89
15 Rasmussen H H, Fallingborg J F, Mortensen P B et al.. Hepatobiliary dysfunction and primary sclerosing cholangitis in patients with Crohn's disease. Scand J Gastroenterol. 1997; 32(6) 604-610
16 Bernstein C N, Blanchard J F, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001; 96(4) 1116-1122
17 Kingham J G, Kochar N, Gravenor M B. Incidence, clinical patterns, and outcomes of primary sclerosing cholangitis in South Wales, United Kingdom. Gastroenterology. 2004; 126(7) 1929-1930
18 Farrant J M, Hayllar K M, Wilkinson M L et al.. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology. 1991; 100(6) 1710-1717
19 Aadland E, Schrumpf E, Fausa O et al.. Primary sclerosing cholangitis: a long-term follow-up study. Scand J Gastroenterol. 1987; 22(6) 655-664
20 Helzberg J H, Petersen J M, Boyer J L. Improved survival with primary sclerosing cholangitis. A review of clinicopathologic features and comparison of symptomatic and asymptomatic patients. Gastroenterology. 1987; 92(6) 1869-1875
21 Porayko M K, Wiesner R H, LaRusso N F et al.. Patients with asymptomatic primary sclerosing cholangitis frequently have progressive disease. Gastroenterology. 1990; 98(6) 1594-1602
22 Bergquist A, Ekbom A, Olsson R et al.. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol. 2002; 36(3) 321-327
23 Farges O, Malassagne B, Sebagh M, Bismuth H. Primary sclerosing cholangitis: liver transplantation or biliary surgery. Surgery. 1995; 117(2) 146-155
24 Broome U, Lofberg R, Veress B, Eriksson L S. Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential. Hepatology. 1995; 22(5) 1404-1408
25 Miros M, Kerlin P, Walker N et al.. Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis before transplantation. Gut. 1991; 32(11) 1369-1373
26 Rosen C B, Nagorney D M, Wiesner R H, Coffey Jr R J, LaRusso N F. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg. 1991; 213(1) 21-25
27 Knechtle S J, D’Alessandro A M, Harms B A et al.. Relationships between sclerosing cholangitis, inflammatory bowel disease, and cancer in patients undergoing liver transplantation. Surgery. 1995; 118(4) 615-619 [discussion 619-620]
28 Kornfeld D, Ekbom A, Ihre T. Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis. A population-based study. Scand J Gastroenterol. 1997; 32(10) 1042-1045
29 Schrumpf E, Abdelnoor M, Fausa O et al.. Risk factors in primary sclerosing cholangitis. J Hepatol. 1994; 21(6) 1061-1066
30 Burak K, Angulo P, Pasha T M et al.. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol. 2004; 99(3) 523-526
31 Levy C, Lymp J, Angulo P et al.. The value of serum CA 19-9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis. Dig Dis Sci. 2005; 50(9) 1734-1740
32 Bjornsson E, Kilander A, Olsson R. CA 19-9 and CEA are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis. Liver. 1999; 19(6) 501-508
33 Rea D J, Heimbach J K, Rosen C B et al.. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005; 242(3) 451-461
34 Bergquist A, Glaumann H, Persson B, Broome U. Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study. Hepatology. 1998; 27(2) 311-316
35 Chalasani N, Baluyut A, Ismail A et al.. Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study. Hepatology. 2000; 31(1) 7-11
36 Bhathal P S, Powell L W. Primary intrahepatic obliterating cholangitis: a possible variant of ‘sclerosing cholangitis’. Gut. 1969; 10(11) 886-893
37 Ludwig J, Barham S S, LaRusso N F et al.. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology. 1981; 1(6) 632-640
38 Wee A, Ludwig J. Pericholangitis in chronic ulcerative colitis: primary sclerosing cholangitis of the small bile ducts?. Ann Intern Med. 1985; 102(5) 581-587
39 Angulo P, Maor-Kendler Y, Lindor K D. Small-duct primary sclerosing cholangitis: a long-term follow-up study. Hepatology. 2002; 35(6) 1494-1500
40 Bjornsson E, Boberg K M, Cullen S et al.. Patients with small duct primary sclerosing cholangitis have a favourable long term prognosis. Gut. 2002; 51(5) 731-735
41 Broome U, Glaumann H, Lindstom E et al.. Natural history and outcome in 32 Swedish patients with small duct primary sclerosing cholangitis (PSC). J Hepatol. 2002; 36(5) 586-589
42 el-Shabrawi M, Wilkinson M L, Portmann B et al.. Primary sclerosing cholangitis in childhood. Gastroenterology. 1987; 92(5 Pt 1) 1226-1235
43 Rabinovitz M, Demetris A J, Bou-Abboud C F, Van Thiel D H. Simultaneous occurrence of primary sclerosing cholangitis and autoimmune chronic active hepatitis in a patient with ulcerative colitis. Dig Dis Sci. 1992; 37(10) 1606-1611
44 Lawrence S P, Sherman K E, Lawson J M, Goodman Z D. A 39 year old man with chronic hepatitis. Semin Liver Dis. 1994; 14(1) 97-105
45 Debray D, Pariente D, Urvoas E, Hadchouel M, Bernard O. Sclerosing cholangitis in children. J Pediatr. 1994; 124(1) 49-56
46 Wilschanski M, Chait P, Wade J A et al.. Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis. Hepatology. 1995; 22(5) 1415-1422
47 Gohlke F, Lohse A W, Dienes H P et al.. Evidence for an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis. J Hepatol. 1996; 24(6) 699-705
48 McNair A N, Moloney M, Portmann B C, Williams R, McFarlane I G. Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases. Am J Gastroenterol. 1998; 93(5) 777-784
49 Gregorio G V, Portmann B, Karani J et al.. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology. 2001; 33(3) 544-553
50 Chazouilleres O. Diagnosis of primary sclerosing cholangitis-autoimmune hepatitis overlap syndrome: to score or not to score?. J Hepatol. 2000; 33(4) 661-663
51 Boberg K M, Fausa O, Haaland T et al.. Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis. Hepatology. 1996; 23(6) 1369-1376
52 Czaja A J. Frequency and nature of the variant syndromes of autoimmune liver disease. Hepatology. 1998; 28(2) 360-365
53 Kaya M, Angulo P, Lindor K D. Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol. 2000; 33(4) 537-542
54 van Buuren H R, van Hoogstraten H JE, Terkivatan T, Schalm S W, Vleggaar F P. High prevalence of autoimmune hepatitis among patients with primary sclerosing cholangitis. J Hepatol. 2000; 33(4) 543-548
55 Alvarez F, Berg P A, Bianchi F B et al.. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999; 31(5) 929-938
56 Floreani A, Rizzotto E R, Ferrara F et al.. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol. 2005; 100(7) 1516-1522
57 Floreani A, Zancan L, Melis A, Baragiotta A, Chiaramonte M. Primary sclerosing cholangitis (PSC): clinical, laboratory and survival analysis in children and adults. Liver. 1999; 19(3) 228-233
58 Feldstein A E, Perrault J, El-Youssif M et al.. Primary sclerosing cholangitis in children: a long-term follow-up study. Hepatology. 2003; 38(1) 210-217
59 Dickson E R, Murtaugh P A, Wiesner R H et al.. Primary sclerosing cholangitis: refinement and validation of survival models. Gastroenterology. 1992; 103(6) 1893-1901
60 Kim W R, Therneau T M, Wiesner R H et al.. A revised natural history model for primary sclerosing cholangitis. Mayo Clin Proc. 2000; 75(7) 688-694
61 Shetty K, Rybicki L, Carey W D. The Child-Pugh classification as a prognostic indicator for survival in primary sclerosing cholangitis. Hepatology. 1997; 25(5) 1049-1053
62 Kim W R, Poterucha J J, Wiesner R H et al.. The relative role of the Child-Pugh classification and the Mayo natural history model in the assessment of survival in patients with primary sclerosing cholangitis. Hepatology. 1999; 29(6) 1643-1648
63 Boberg K M, Rocca G, Egeland T et al.. Time-dependent Cox regression model is superior in prediction of prognosis in primary sclerosing cholangitis. Hepatology. 2002; 35(3) 652-657
64 Boberg K M, Mitchell S, Broome U et al.. Natural history of primary sclerosing cholangitis. A long term follow-up study of 394 European primary sclerosing cholangitis patients. J Hepatol. 2000; 32(suppl 2) 32A
65 Ismail T, Angrisani L, Powell J E et al.. Primary sclerosing cholangitis: surgical options, prognostic variables and outcome. Br J Surg. 1991; 78(5) 564-567
66 Roberts M S, Angus D C, Bryce C L, Valenta Z, Weissfeld L. Survival after liver transplantation in the United States: a disease-specific analysis of the UNOS database. Liver Transpl. 2004; 10(7) 886-897
67 Narumi S, Roberts J P, Emond J C, Lake J, Ascher N L. Liver transplantation for sclerosing cholangitis. Hepatology. 1995; 22(2) 451-457
68 Goss J A, Shackleton C R, Farmer D G et al.. Orthotopic liver transplantation for primary sclerosing cholangitis. A 12-year single center experience. Ann Surg. 1997; 225(5) 472-481 discussion 481-473
69 Saldeen K, Friman S, Olausson M, Olsson R. Follow-up after liver transplantation for primary sclerosing cholangitis: effects on survival, quality of life, and colitis. Scand J Gastroenterol. 1999; 34(5) 535-540
70 Graziadei I W, Wiesner R H, Batts K P et al.. Recurrence of primary sclerosing cholangitis following liver transplantation. Hepatology. 1999; 29(4) 1050-1056
71 Liden H, Norrby J, Gabel M, Friman S, Olausson M. Outcome after liver transplantation for primary sclerosing cholangitis. Transplant Proc. 2001; 33(4) 2452-2453
72 Solano E, Khakhar A, Bloch M et al.. Liver transplantation for primary sclerosing cholangitis. Transplant Proc. 2003; 35(7) 2431-2434
73 Maheshwari A, Yoo H Y, Thuluvath P J. Long-term outcome of liver transplantation in patients with PSC: a comparative analysis with PBC. Am J Gastroenterol. 2004; 99(3) 538-542
74 Brandsaeter B, Isoniemi H, Broome U et al.. Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy. J Hepatol. 2004; 40(5) 815-822
75 Vera A, Moledina S, Gunson B et al.. Risk factors for recurrence of primary sclerosing cholangitis of liver allograft. Lancet. 2002; 360(9349) 1943-1944
76 Lee Y M. Motion-patients with primary sclerosing cholangitis should undergo early liver transplantation: arguments for the motion. Can J Gastroenterol. 2002; 16(10) 697-699
77 Nashan B, Schlitt H J, Tusch G et al.. Biliary malignancies in primary sclerosing cholangitis: timing for liver transplantation. Hepatology. 1996; 23(5) 1105-1111
78 Ricci P, Therneau T M, Malinchoc M et al.. A prognostic model for the outcome of liver transplantation in patients with cholestatic liver disease. Hepatology. 1997; 25(3) 672-677
79 Wiesner R H, Porayko M K, Hay J E et al.. Liver transplantation for primary sclerosing cholangitis: impact of risk factors on outcome. Liver Transpl Surg. 1996; 2(5 suppl 1) 99-108
80 Neuberger J, Gunson B, Komolmit P, Davies M H, Christensen E. Pretransplant prediction of prognosis after liver transplantation in primary sclerosing cholangitis using a Cox regression model. Hepatology. 1999; 29(5) 1375-1379
81 Lucey M R, Brown K A, Everson G T et al.. Minimal criteria for placement of adults on the liver transplant waiting list: a report of a national conference organized by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases. Liver Transpl Surg. 1997; 3(6) 628-637
82 Talwalkar J A, Seaberg E, Kim W R, Wiesner R H. Predicting clinical and economic outcomes after liver transplantation using the Mayo primary sclerosing cholangitis model and Child-Pugh score. National Institutes of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database Group. Liver Transpl. 2000; 6(6) 753-758
83 Kamath P S, Wiesner R H, Malinchoc M et al.. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001; 33(2) 464-470
84 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. 2003; 9(9) 961-969
85 Khettry U, Keaveny A, Goldar-Najafi A et al.. Liver transplantation for primary sclerosing cholangitis: a long-term clinicopathologic study. Hum Pathol. 2003; 34(11) 1127-1136
86 Kugelmas M, Spiegelman P, Osgood M J et al.. Different immunosuppressive regimens and recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl. 2003; 9(7) 727-732
87 Sheng R, Campbell W L, Zajko A B, Baron R L. Cholangiographic features of biliary strictures after liver transplantation for primary sclerosing cholangitis: evidence of recurrent disease. AJR Am J Roentgenol. 1996; 166(5) 1109-1113
88 Harrison R F, Davies M H, Neuberger J M, Hubscher S G. Fibrous and obliterative cholangitis in liver allografts: evidence of recurrent primary sclerosing cholangitis?. Hepatology. 1994; 20(2) 356-361
89 Jeyarajah D R, Netto G J, Lee S P et al.. Recurrent primary sclerosing cholangitis after orthotopic liver transplantation: is chronic rejection part of the disease process?. Transplantation. 1998; 66(10) 1300-1306
90 Kubota T, Thomson A, Clouston A D et al.. Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation. J Hepatobiliary Pancreat Surg. 1999; 6(4) 377-381
91 Yusoff I F, House A K, De Boer W B et al.. Disease recurrence after liver transplantation in Western Australia. J Gastroenterol Hepatol. 2002; 17(2) 203-207
92 MacLean A R, Lilly L, Cohen Z, O'Connor B, McLeod R S. Outcome of patients undergoing liver transplantation for primary sclerosing cholangitis. Dis Colon Rectum. 2003; 46(8) 1124-1128
93 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. 2005; 11(11) 1361-1369
94 Bjoro K, Schrumpf E. Liver transplantation for primary sclerosing cholangitis. J Hepatol. 2004; 40(4) 570-577
95 Wiesner R H. Liver transplantation for primary sclerosing cholangitis: timing, outcome, impact of inflammatory bowel disease and recurrence of disease. Best Pract Res Clin Gastroenterol. 2001; 15(4) 667-680

Keith D LindorM.D.

Division of Gastroenterology and Hepatology, Mayo Foundation

200 1st Street SW, Rochester, MN 55905

Email: lindor.keith@mayo.edu