Primary sclerosing cholangitis: Inflammatory bowel disease and colorectal cancer
- Kris V Kowdley, MD, FACP, FACG, FASGE, AGAF
Kris V Kowdley, MD, FACP, FACG, FASGE, AGAF
- Clinical Professor of Medicine
- University of Washington School of Medicine
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. The majority of patients with PSC have underlying inflammatory bowel disease (IBD). Patients with concurrent PSC and IBD have an increased risk of colorectal cancer (CRC) [1-6]. This topic review will focus on the epidemiology, pathogenesis, clinical features, diagnosis, and management of IBD in patients with PSC in addition to the risk of CRC and guidelines for CRC surveillance. CRC surveillance in patients with IBD is presented separately. (See "Colorectal cancer surveillance in inflammatory bowel disease".)
INFLAMMATORY BOWEL DISEASE
Epidemiology — The prevalence of inflammatory bowel disease (IBD) in patients with primary sclerosing cholangitis (PSC) approaches 90 percent [7,8]. Ulcerative colitis (UC), Crohn disease (CD), and indeterminate colitis of the colon account for 80, 10, and 10 percent, respectively . (See "Primary sclerosing cholangitis: Epidemiology and pathogenesis", section on 'PSC and inflammatory bowel disease'.)
Clinical features — Colitis in patients with PSC often presents at an earlier age as compared with patients with IBD alone . The colitis usually has a mild or quiescent course. Patients are often asymptomatic but in rare cases present with rectal bleeding. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults", section on 'Colitis' and "Clinical manifestations, diagnosis and prognosis of Crohn disease in adults", section on 'Clinical manifestations'.)
Following colectomy, patients can present with stomal and peristomal variceal bleeding secondary to portal hypertension associated with PSC. Patients with proctocolectomy with ileal pouch anal anastomosis also have an increased risk of pouchitis [9,11,12]. Symptoms of pouchitis include increased stool frequency, urgency, abdominal cramps, pelvic pressure, tenesmus, and night-time fecal seepage to incontinence. (See "Routine care of patients with an ileostomy or colostomy and management of ostomy complications", section on 'Stomal bleeding' and "Pouchitis: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)
The course of colitis following liver transplantation for PSC is variable. Although the colitis may remain quiescent in some patients, other patients may have severe symptoms (10 or more stools per day with severe cramps and continuous bleeding) despite the immunosuppression used for the transplant [13-15]. (See "Primary sclerosing cholangitis in adults: Management", section on 'Inflammatory bowel disease' and "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults", section on 'Colitis'.)
- 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 1996; 110:331.
- Broomé U, Löfberg R, Veress B, Eriksson LS. Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential. Hepatology 1995; 22:1404.
- Shetty K, Rybicki L, Brzezinski A, et al. The risk for cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis. Am J Gastroenterol 1999; 94:1643.
- 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 1997; 41:522.
- Gurbuz AK, Giardiello FM, Bayless TM. Colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Dis Colon Rectum 1995; 38:37.
- D'Haens GR, Lashner BA, Hanauer SB. Pericholangitis and sclerosing cholangitis are risk factors for dysplasia and cancer in ulcerative colitis. Am J Gastroenterol 1993; 88:1174.
- Fausa O, Schrumpf E, Elgjo K. Relationship of inflammatory bowel disease and primary sclerosing cholangitis. Semin Liver Dis 1991; 11:31.
- Tung BY, Brentnall TA, Kowdley KV, et al. Diagnosis and prevalence of ulcerative colitis in patients with sclerosing cholangitis (abstract). Hepatology 1996; 24:169A.
- Loftus EV Jr, Harewood GC, Loftus CG, et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut 2005; 54:91.
- Joo M, Abreu-e-Lima P, Farraye F, et al. Pathologic features of ulcerative colitis in patients with primary sclerosing cholangitis: a case-control study. Am J Surg Pathol 2009; 33:854.
- Lundqvist K, Broomé U. Differences in colonic disease activity in patients with ulcerative colitis with and without primary sclerosing cholangitis: a case control study. Dis Colon Rectum 1997; 40:451.
- 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 1996; 38:234.
- Dvorchik I, Subotin M, Demetris AJ, et al. Effect of liver transplantation on inflammatory bowel disease in patients with primary sclerosing cholangitis. Hepatology 2002; 35:380.
- Jørgensen KK, Lindström L, Cvancarova M, et al. Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease. Clin Gastroenterol Hepatol 2013; 11:517.
- Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005; 19 Suppl A:5A.
- Jørgensen KK, Grzyb K, Lundin KE, et al. Inflammatory bowel disease in patients with primary sclerosing cholangitis: clinical characterization in liver transplanted and nontransplanted patients. Inflamm Bowel Dis 2012; 18:536.
- Chapman R, Fevery J, Kalloo A, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology 2010; 51:660.
- Bergeron V, Vienne A, Sokol H, et al. Risk factors for neoplasia in inflammatory bowel disease patients with pancolitis. Am J Gastroenterol 2010; 105:2405.
- Marchesa P, Lashner BA, Lavery IC, et al. The risk of cancer and dysplasia among ulcerative colitis patients with primary sclerosing cholangitis. Am J Gastroenterol 1997; 92:1285.
- Lindberg BU, Broomé U, Persson B. Proximal colorectal dysplasia or cancer in ulcerative colitis. The impact of primary sclerosing cholangitis and sulfasalazine: results from a 20-year surveillance study. Dis Colon Rectum 2001; 44:77.
- Claessen MM, Vleggaar FP, Tytgat KM, et al. High lifetime risk of cancer in primary sclerosing cholangitis. J Hepatol 2009; 50:158.
- Soetikno RM, Lin OS, Heidenreich PA, et al. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc 2002; 56:48.
- Zheng HH, Jiang XL. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies. Eur J Gastroenterol Hepatol 2016; 28:383.
- Hanouneh IA, Macaron C, Lopez R, et al. Risk of colonic neoplasia after liver transplantation for primary sclerosing cholangitis. Inflamm Bowel Dis 2012; 18:269.
- Singh S, Edakkanambeth Varayil J, Loftus EV Jr, Talwalkar JA. Incidence of colorectal cancer after liver transplantation for primary sclerosing cholangitis: a systematic review and meta-analysis. Liver Transpl 2013; 19:1361.
- Ochsenkühn T, Bayerdörffer E, Meining A, et al. Colonic mucosal proliferation is related to serum deoxycholic acid levels. Cancer 1999; 85:1664.
- 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 1998; 31:111.
- Bayerdörffer E, Mannes GA, Richter WO, et al. Increased serum deoxycholic acid levels in men with colorectal adenomas. Gastroenterology 1993; 104:145.
- Stadler J, Yeung KS, Furrer R, et al. Proliferative activity of rectal mucosa and soluble fecal bile acids in patients with normal colons and in patients with colonic polyps or cancer. Cancer Lett 1988; 38:315.
- Reddy BS, Wynder EL. Metabolic epidemiology of colon cancer. Fecal bile acids and neutral sterols in colon cancer patients and patients with adenomatous polyps. Cancer 1977; 39:2533.
- Hill MJ, Melville DM, Lennard-Jones JE, et al. Faecal bile acids, dysplasia, and carcinoma in ulcerative colitis. Lancet 1987; 2:185.
- Farraye FA, Odze RD, Eaden J, Itzkowitz SH. AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010; 138:746.
- Lindor KD, Kowdley KV, Harrison ME, American College of Gastroenterology. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol 2015; 110:646.
- Cairns SR, Scholefield JH, Steele RJ, et al. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut 2010; 59:666.
- Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011; 60:571.
- Fevery J, Henckaerts L, Van Oirbeek R, et al. Malignancies and mortality in 200 patients with primary sclerosering cholangitis: a long-term single-centre study. Liver Int 2012; 32:214.
- Narisawa T, Fukaura Y, Terada K, Sekiguchi H. Prevention of N-methylnitrosourea-induced colon tumorigenesis by ursodeoxycholic acid in F344 rats. Jpn J Cancer Res 1998; 89:1009.
- Earnest DL, Holubec H, Wali RK, et al. Chemoprevention of azoxymethane-induced colonic carcinogenesis by supplemental dietary ursodeoxycholic acid. Cancer Res 1994; 54:5071.
- Rodrigues CM, Kren BT, Steer CJ, Setchell KD. The site-specific delivery of ursodeoxycholic acid to the rat colon by sulfate conjugation. Gastroenterology 1995; 109:1835.
- Narisawa T, Fukaura Y, Terada K, Sekiguchi H. Inhibitory effects of ursodeoxycholic acid on N-methylnitrosourea-induced colon carcinogenesis and colonic mucosal telomerase activity in F344 rats. J Exp Clin Cancer Res 1999; 18:259.
- Krishna-Subramanian S, Hanski ML, Loddenkemper C, et al. UDCA slows down intestinal cell proliferation by inducing high and sustained ERK phosphorylation. Int J Cancer 2012; 130:2771.
- Tung BY, Emond MJ, Haggitt RC, et al. Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Ann Intern Med 2001; 134:89.
- Pardi DS, Loftus EV Jr, Kremers WK, et al. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology 2003; 124:889.
- Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med 1997; 336:691.
- Eaton JE, Silveira MG, Pardi DS, 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.
- Lashner BA, Provencher KS, Seidner DL, et al. The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Gastroenterology 1997; 112:29.
- INFLAMMATORY BOWEL DISEASE
- Clinical manifestations
- - Clinical features
- - Endoscopic features
- Differential diagnosis
- COLORECTAL CANCER
- Clinical features
- - Colorectal cancer screening
- PSC and IBD
- PSC without IBD
- - Chemoprevention
- SUMMARY AND RECOMMENDATIONS