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Hepatobiliary manifestations of inflammatory bowel disease

Gad Friedman, MD, FRCPC
Alain Bitton, MD, FRCPC
Section Editor
Paul Rutgeerts, MD, PhD, FRCP
Deputy Editor
Kristen M Robson, MD, MBA, FACG


Diseases of the liver and biliary tract are common extraintestinal manifestations of inflammatory bowel disease (IBD) (table 1) [1-3]. Primary sclerosing cholangitis (PSC) is one of the more common hepatobiliary complications of IBD, particularly in patients with ulcerative colitis. It is estimated that approximately 5 percent of patients with ulcerative colitis develop PSC and that ulcerative colitis is present in up to 90 percent of patients with PSC [4]. (See "Primary sclerosing cholangitis: Epidemiology and pathogenesis".)

Abnormal liver biochemical tests are present in up to 30 percent of patients with IBD and do not appear to correlate with disease activity [5]. As a result, persistently abnormal liver biochemical tests should generally be evaluated. This topic review will focus upon the other hepatobiliary manifestations that can occur in patients with IBD. The association of IBD with PSC is discussed elsewhere. (See "Primary sclerosing cholangitis: Epidemiology and pathogenesis", section on 'PSC and inflammatory bowel disease'.)


Most of the drugs used in the medical management of inflammatory bowel disease (IBD) have been associated with liver toxicity, although the overall incidence of serious complications is low [6,7]. The following are among the reactions that can be seen:

Sulfasalazine can cause both hepatocellular and cholestatic enzyme abnormalities, often related to a hypersensitivity reaction. Newer sulfa-free aminosalicylate preparations deliver increased amounts of the pharmacologically active ingredient of sulfasalazine (5-aminosalicylic acid [5-ASA], mesalamine) to the site of active bowel disease and are associated with a lower systemic toxicity. 5-ASA can rarely cause pancreatitis. (See "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease".)

Azathioprine can cause a spectrum of hepatic injury, ranging from asymptomatic aminotransferase elevations (in approximately 5 percent of patients) to cholestasis, veno-occlusive disease, and peliosis hepatis. Mercaptopurine (6-MP), a metabolite of azathioprine, can also cause hepatocellular and cholestatic hepatitis. Thus, patients treated with azathioprine or 6-MP should have their liver biochemistries monitored regularly. Liver abnormalities usually resolve after discontinuation of therapy. (See "Immunomodulator therapy in Crohn disease", section on 'Toxicity'.)

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Literature review current through: Nov 2017. | This topic last updated: Jul 10, 2017.
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  1. Raj V, Lichtenstein DR. Hepatobiliary manifestations of inflammatory bowel disease. Gastroenterol Clin North Am 1999; 28:491.
  2. Riegler G, D'Incà R, Sturniolo GC, et al. Hepatobiliary alterations in patients with inflammatory bowel disease: a multicenter study. Caprilli & Gruppo Italiano Studio Colon-Retto. Scand J Gastroenterol 1998; 33:93.
  3. Wewer V, Gluud C, Schlichting P, et al. Prevalence of hepatobiliary dysfunction in a regional group of patients with chronic inflammatory bowel disease. Scand J Gastroenterol 1991; 26:97.
  4. Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med 1995; 332:924.
  5. Mendes FD, Levy C, Enders FB, et al. Abnormal hepatic biochemistries in patients with inflammatory bowel disease. Am J Gastroenterol 2007; 102:344.
  6. Stricker BH. Drug-Induced Hepatic Injury, 2nd ed, Elsevier, New York 1992.
  7. Gisbert JP, Luna M, González-Lama Y, et al. Liver injury in inflammatory bowel disease: long-term follow-up study of 786 patients. Inflamm Bowel Dis 2007; 13:1106.
  8. Dubinsky MC, Vasiliauskas EA, Singh H, et al. 6-thioguanine can cause serious liver injury in inflammatory bowel disease patients. Gastroenterology 2003; 125:298.
  9. Ferlitsch A, Teml A, Reinisch W, et al. 6-thioguanine associated nodular regenerative hyperplasia in patients with inflammatory bowel disease may induce portal hypertension. Am J Gastroenterol 2007; 102:2495.
  10. Kremer JM. Liver toxicity does not have to follow methotrexate therapy of patients with rheumatoid arthritis. Am J Gastroenterol 1997; 92:194.
  11. Barbero-Villares A, Mendoza Jiménez-Ridruejo J, Taxonera C, et al. Evaluation of liver fibrosis by transient elastography (Fibroscan®) in patients with inflammatory bowel disease treated with methotrexate: a multicentric trial. Scand J Gastroenterol 2012; 47:575.
  12. Coté T. TNF Blocker Safety: Lymphoma and Liver Failure. Federal Drug Administration, March 4, 2003.
  13. Shelton E, Chaudrey K, Sauk J, et al. New onset idiosyncratic liver enzyme elevations with biological therapy in inflammatory bowel disease. Aliment Pharmacol Ther 2015; 41:972.
  14. Tobon GJ, Cañas C, Jaller JJ, et al. Serious liver disease induced by infliximab. Clin Rheumatol 2007; 26:578.
  15. Menghini VV, Arora AS. Infliximab-associated reversible cholestatic liver disease. Mayo Clin Proc 2001; 76:84.
  16. Ierardi E, Della Valle N, Nacchiero MC, et al. Infliximab single administration followed by acute liver injury. Inflamm Bowel Dis 2006; 12:1089.
  17. Adar T, Mizrahi M, Pappo O, et al. Adalimumab-induced autoimmune hepatitis. J Clin Gastroenterol 2010; 44:e20.
  18. Hagel S, Bruns T, Theis B, et al. Subacute liver failure induced by adalimumab. Int J Clin Pharmacol Ther 2011; 49:38.
  19. Parente F, Pastore L, Bargiggia S, et al. Incidence and risk factors for gallstones in patients with inflammatory bowel disease: a large case-control study. Hepatology 2007; 45:1267.
  20. Maurer P, Haag K, Roth M, et al. No evidence for abnormal gallbladder emptying in Crohn's disease. Hepatogastroenterology 1996; 43:807.
  21. Mibu R, Makino I, Chijiiwa K. Gallstones and their composition in patients with ileoanal anastomosis. J Gastroenterol 1995; 30:413.
  22. Greenstein AJ, Sachar DB, Panday AK, et al. Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients. Medicine (Baltimore) 1992; 71:261.
  23. Meyers S, Janowitz HD, Gumaste VV, et al. Colchicine therapy of the renal amyloidosis of ulcerative colitis. Gastroenterology 1988; 94:1503.
  24. Vakil N, Hayne G, Sharma A, et al. Liver abscess in Crohn's disease. Am J Gastroenterol 1994; 89:1090.
  25. Mir-Madjlessi SH, McHenry MC, Farmer RG. Liver abscess in Crohn's disease. Report of four cases and review of the literature. Gastroenterology 1986; 91:987.
  26. Bermejo F, Lopez-Sanroman A, Taxonera C, et al. Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis. Aliment Pharmacol Ther 2008; 28:623.
  27. Xiao WB, Liu YL. Primary biliary cirrhosis and ulcerative colitis: a case report and review of literature. World J Gastroenterol 2003; 9:878.
  28. Koulentaki M, Koutroubakis IE, Petinaki E, et al. Ulcerative colitis associated with primary biliary cirrhosis. Dig Dis Sci 1999; 44:1953.
  29. Arai O, Ikeda H, Mouri H, et al. Two cases of inflammatory bowel disease diagnosed in the course of primary biliary cirrhosis. Nihon Shokakibyo Gakkai Zasshi 2010; 107:900.
  30. Ohge H, Takesue Y, Yokoyama T, et al. Progression of primary biliary cirrhosis after proctocolectomy for ulcerative colitis. J Gastroenterol 2000; 35:870.
  31. Onishi S, Sakamaki T, Maeda T, et al. DNA typing of HLA class II genes; DRB1*0803 increases the susceptibility of Japanese to primary biliary cirrhosis. J Hepatol 1994; 21:1053.