Clinical Review
Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease
Udayakumar Navaneethan MD,
Bo Shen MD,
Udayakumar Navaneethan MD
Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio
Search for more papers by this authorCorresponding Author
Bo Shen MD
Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio
Digestive Disease Institute-Desk A31, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195Search for more papers by this authorUdayakumar Navaneethan MD,
Bo Shen MD,
Udayakumar Navaneethan MD
Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio
Search for more papers by this authorCorresponding Author
Bo Shen MD
Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio
Digestive Disease Institute-Desk A31, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195Search for more papers by this authorAbstract
Abstract: Diseases involving the hepatopancreatobiliary (HPB) system are frequently encountered in patients with inflammatory bowel disease (IBD). Hepatobiliary manifestations constitute some of the most common extraintestinal manifestations of IBD. They appear to occur with similar frequency in patients with Crohn's disease or ulcerative colitis. HPB manifestations may occur in following settings: 1) disease possibly associated with a shared pathogenetic mechanism with IBD including primary sclerosing cholangitis (PSC), small-duct PSC/pericholangitis and PSC/autoimmune hepatitis overlap, acute and chronic pancreatitis related to IBD; 2) diseases which parallel structural and physiological changes seen with IBD, including cholelithiasis, portal vein thrombosis, and hepatic abscess; and 3) diseases related to adverse effects associated with treatment of IBD, including drug-induced hepatitis, pancreatitis (purine-based agents), or liver cirrhosis (methotrexate), and reactivation of hepatitis B, and biologic agent-associated hepatosplenic lymphoma. Less common HPB manifestations that have been described in association with IBD include autoimmune pancreatitis (AIP), IgG4-associated cholangitis (IAC), primary biliary cirrhosis (PBC), fatty liver, granulomatous hepatitis, and amyloidosis. PSC is the most significant hepatobiliary manifestation associated with IBD and poses substantial challenges in management requiring a multidisciplinary approach. The natural disease course of PSC may progress to cirrhosis and ultimately require liver transplantation in spite of total proctocolectomy with ileal-pouch anal anastomosis. The association between AIP, IAC, and elevated serum IgG4 in patients with PSC is intriguing. The recently reported association between IAC and IBD may open the door to investigate these complex disorders. Further studies are warranted to help understand the pathogenesis of HPB manifestations associated with IBD, which would help clinicians better manage these patients. An interdisciplinary approach, involving gastroenterologists, hepatologists, and, in advanced cases, general, colorectal, and transplant surgeons is advocated. (Inflamm Bowel Dis 2010)
REFERENCES
- 1 Bernstein CN, Blanchard JF, Rawsthorne P, et al. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001; 96: 1116–1122.
- 2 Ricart E, Panaccione R, Loftus EV Jr, et al. Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study. Inflamm Bowel Dis. 2004; 10: 207–214.
- 3 Bernstein CN, Wajda A, Blanchard JF. The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study. Gastroenterology. 2005; 129: 827–836.
- 4 Mendoza JL, Lana R, Taxonera C, et al. Extraintestinal manifestations in inflammatory bowel disease: differences between Crohn's disease and ulcerative colitis. Med Clin (Barc). 2005; 125: 297–300.
- 5 Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn's disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore). 1976; 55: 401–412.
- 6 Olsson R, Danielsson A, Jarnerot G, et al. Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. Gastroenterology. 1991; 100: 1319–1323.
- 7 Smith M, Loe S. Sclerosing cholangitis: review of recent case reports and associated diseases and four new cases. Am J Surg. 1965; 110: 239–246.
- 8 Broomé U, Bergquist A. Primary sclerosing cholangitis, inflammatory bowel disease, and colon cancer. Semin Liver Dis. 2006; 26: 31–40.
- 9 Loftus EV, Sandborn WJ, Lindor KD, et al. Interactions between chronic liver disease and inflammatory bowel disease. Inflamm Bowel Dis. 1997; 3: 288–302.
- 10 Faubion WA, Loftus EV, Sandborn WJ, et al. Pediatric “PSC-IBD”: a descriptive report of associated inflammatory bowel disease among pediatric patients with PSC. J Pediatr Gastroenterol Nutr. 2001; 33: 296–300.
- 11 Loftus EV, Harewood GC, Loftus CG, et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut. 2005; 54: 91–96.
- 12 Heuschen U, Hinz U, Allemeyer E, et al. Backwash ileitis is strongly associated with colorectal carcinoma in ulcerative colitis. Gastroenterology. 2001; 120: 841–847.
- 13 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: 854–862.
- 14 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: 451–456.
- 15 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: 234–239.
- 16 Broome U, Lofberg R, Lundqvist K, et al. Subclinical time span of inflammatory bowel disease in patients with primary sclerosing cholangitis. Dis Colon Rectum. 1995; 38: 1301–1305.
- 17 Soetikno R, Lin O, Heidenreich P. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc. 2002; 56: 48–54.
- 18 Chapman RW, Marborgh BA, Rhodes JM, et al. Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology. Gut. 1980; 21: 870–877.
- 19 Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med. 1995; 332: 924–933.
- 20 Helzberg JH, Peterson JM, Boyer JL. Improved survival with primary sclerosing cholangitis: a review of clinicopathologic features and comparison of symptomatic and asymptomatic patients. Gastroenterology. 1987; 92: 1869–1875.
- 21 Schrumpf E, Elgjo K, Fausa O, et al. Sclerosing cholangitis in ulcerative colitis. Scand J Gastroenterol. 1980; 15: 689–697.
- 22 Shepherd HA, Selby WS, Chapman RW, et al. Ulcerative colitis and persistent liver dysfunction. Q J Med. 1983; 52: 503–513.
- 23 Rasmussen HH, Fallingborg JF, Mortensen PB, et al. Hepatobiliary dysfunction and primary sclerosing cholangitis in patients with Crohn's disease. Scand J Gastroenterol. 1997; 32: 604–610.
- 24 Freeman K, Bennett AE, Lopez R, et al. Primary sclerosing cholangitis is associated with endoscopic and histologic backwash ileitis in patients with ileal pouch-anal anastomosis. Gastroenterology. 2008; 134( suppl 1): A344.
- 25 Takikawa H, Manabe T. Primary sclerosing cholangitis in Japan—analysis of 192 cases. J Gastroenterol. 1997; 32: 134–137.
- 26 Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults. American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 1997; 92: 204–211.
- 27 Bernstein CN, Eaden J, Steinhart AH, et al. Cancer prevention in inflammatory bowel disease and the chemoprophylactic potential of 5-aminosalicylic acid. Inflamm Bowel Dis. 2002; 8: 356–361.
- 28 Bleday R, Lee E, Jessurun J, et al. Increased risk of early colorectal neoplasms after hepatic transplant in patients with inflammatory bowel disease. Dis Colon Rectum. 1993; 36: 908–912.
- 29 Higashi H, Yanaga K, Marsh JW, et al. Development of colon cancer after liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. Hepatology. 1990; 11: 477–480.
- 30 Rutter MD, Saunders BP, Wilkinson KH, et al. Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk. Gut. 2004; 53: 1813–1816.
- 31 Stahlberg D, Veress B, Tribukait B, et al. Atrophy and neoplastic transformation of the ileal pouch mucosa in patients with ulcerative colitis and primary sclerosing cholangitis: a case control study. Dis Colon Rectum. 2003; 46: 770–778.
- 32 Ludwig J, Barham SS, La Russo NF, et al. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology. 1981; 1: 632–640.
- 33 MacCarty RL, La Russo NF, May GR, et al. Cholangiocarcinoma complicating primary sclerosing cholangitis: cholangiographic appearances. Radiology. 1985; 156: 43–46.
- 34 Broomé U, Olsson R, Loof L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996; 38: 610–615.
- 35 Rabinovitz M, Gavaler JS, Schade RR, et al. Does primary sclerosing cholangitis occurring in association with inflammatory bowel disease differ from that occurring in the absence of inflammatory bowel disease? A study of sixty-six subjects. Hepatology. 1990; 11: 7–11.
- 36 Farrant JM, Doherty DG, Donaldson PT, et al. Amino acid substitutions at positions 38 of the DR beta polypeptide confer susceptibility to and protection from primary sclerosing cholangitis. Hepatology. 1992; 16: 390–395.
- 37 Olerup O, Olsson R, Hultcrantz R, et al. HLA-DR and HLA-DQ are not markers for rapid disease progression in primary sclerosing cholangitis. Gastroenterology. 1995; 108: 870–878.
- 38 Saarinen S, Olerup O, Broome U. Increased frequency of autoimmune diseases in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2000; 95: 3195–3199.
- 39 Mulder AH, Horst G, Haagsma EB, et al. Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver diseases. Hepatology. 1993; 17: 411–417.
- 40 Bansi DS, Fleming KA, Chapman RW. Importance of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis and ulcerative colitis: prevalence, titre, and IgG subclass. Gut. 1996; 38: 384–389.
- 41 Terjung B, Spengler U. Role of auto-antibodies for the diagnosis of chronic cholestatic liver diseases. Clin Rev Allergy Immunol. 2005; 28: 115–133.
- 42 Terjung B, Spengler U, Sauerbruch T, et al. “Atypical p-ANCA” in IBD and hepatobiliary disorders react with a 50-kilodalton nuclear envelope protein of neutrophils and myeloid cell lines. Gastroenterology. 2000; 119: 310–322.
- 43 Mandal A, Dasgupta A, Jeffers L, et al. Autoantibodies in sclerosing cholangitis against a shared peptide in biliary and colon epithelium. Gastroenterology. 1994; 106: 185–192.
- 44 O'Mahony CA, Vierling JM. Etiopathogenesis of primary sclerosing cholangitis. Semin Liver Dis. 2006; 26: 3–21.
- 45 Worthington J, Cullen S, Chapman R. Immunopathogenesis of primary sclerosing cholangitis. Clin Rev Allergy Immunol. 2005; 28: 93–103.
- 46 Fausa O, Schrumpf E, Elgio K. Relationship of inflammatory bowel disease and primary sclerosing cholangitis. Semin Liver Dis. 1991; 11: 31–39.
- 47 Aoki CA, Bowlus CL, Gershwin ME. The immunobiology of primary sclerosing cholangitis. Autoimmun Rev. 2005; 4: 137–143.
- 48 Kono K, Ohnishi K, Omata K, et al. Experimental portal fibrosis produced by intraportal injection of killed nonpathogenic Escherichia coli in rabbits. Gastroenterology. 1988; 94: 787–796.
- 49 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. 2000; 47: 1504–1508.
- 50 Terjung B, Muennich M, Gottwein J, et al. Identification of myeloid-specific tubulin-beta isotype 5 as target antigen of antineutrophil cytoplasmic antibodies in autoimmune liver disorders. Hepatology. 2005; 42( suppl 1): 288A.
- 51 Erickson HP. FtsZ, a prokaryotic homolog of tubulin? Cell. 1995; 80: 367–370.
- 52 Terjung B, Spengler U. Atypical p-ANCA in PSC and AIH: a hint toward a “leaky gut”? Clin Rev Allergy Immunol. 2009; 36: 40–51.
- 53 Tischendorf JJ, Hecker H, Kruger M, et al. Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am J Gastroenterol. 2007; 102: 107–114.
- 54 Wiesner RH, Grambsch PM, Dickson ER, et al. Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis. Hepatology. 1989; 10: 430–436.
- 55 Talwalkar JA, Lindor KD. Primary sclerosing cholangitis. Inflamm Bowel Dis. 2005; 11: 62–72.
- 56 Heikius B, Niemela S, Lehtola J, et al. Hepatobiliary and coexisting pancreatic duct abnormalities in patients with inflammatory bowel disease. Scand J Gastroenterol. 1997; 32: 153–161.
- 57 Navaneethan U, Remzi FH, Nutter B, et al. Risk Factors for Abnormal Liver Function Tests in Patients With Ileal Pouch-Anal Anastomosis for Underlying Inflammatory Bowel Disease. Am J Gastroenterol. 2009; 104: 2467–2475.
- 58 MacCarty RL, LaRusso NF, Wiesner RH, et al. Primary sclerosing cholangitis: findings on cholangiography and pancreatography. Radiology. 1983; 149: 39–44.
- 59 Moreno Luna LE, Gores GJ. Advances in the diagnosis of cholangiocarcinoma in patients with primary sclerosing cholangitis. Liver Transpl. 2006; 12 ( 11 Suppl 2): S15–19.
- 60 Fulcher AS, Turner MA, Franklin KJ, et al. Primary sclerosing cholangitis: evaluation with MR cholangiography — a case-control study. Radiology. 2000; 215: 71–80.
- 61 Angulo P, Pearce DH, Johnson CD, et al. Magnetic resonance cholangiography in patients with biliary disease: its role in primary sclerosing cholangitis. J Hepatol. 2000; 33: 520–527.
- 62 Moff SL, Kamel IR, Eustace J, et al. Diagnosis of primary sclerosing cholangitis: a blinded comparative study using magnetic resonance Cholangiography and endoscopic retrograde cholangiography. Gastrointest Endosc. 2006; 64: 219–223.
- 63 Berstad AE, Aabakken L, Smith HJ, et al. Diagnostic accuracy of magnetic resonance and endoscopic retrograde cholangiography in primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 2006; 4: 514–520.
- 64 Textor HJ, Flacke S, Pauleit D, et al. Three-dimensional magnetic resonance cholangiopancreatography with respiratory triggering in the diagnosis of primary sclerosing cholangitis: comparison with endoscopic retrograde cholangiography. Endoscopy. 2002; 34: 984–990.
- 65 Burak KW, Angulo P, Lindor KD. Is there a role for liver biopsy in primary sclerosing cholangitis? Am J Gastroenterol. 2003; 98: 1155–1158.
- 66 Charatcharoenwitthaya P, Enders FB, Halling KC, et al. Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis. Hepatology. 2008; 48: 1106–1117.
- 67 Rea DJ, Heimbach JK, Rosen CB, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005; 242: 451–458.
- 68 Parsi MA, Li A, Li CP, et al. DNA methylation alterations in endoscopic retrograde cholangiopancreatography brush samples of patients with suspected pancreaticobiliary disease. Clin Gastroenterol Hepatol. 2008; 6: 1270–1278.
- 69 Cohen S, Bacon BR, Berlin JA, et al. National Institutes of Health State-of-the-Science Conference Statement: ERCP for diagnosis and therapy, January 14–16, 2002. Gastrointest Endosc. 2002; 56: 803–809.
- 70 Porayko MK, Wiesner RH, LaRusso NF, et al. Patients with asymptomatic primary sclerosing cholangitis frequently have progressive disease. Gastroenterology. 1990; 98: 1594–1602.
- 71 Farrant JM, Hayllar KM, Wilkinson ML, et al. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology. 1991; 100: 1710–1717.
- 72 Ponsioen CY, Vrouenraets SM, Prawirodirdjo W, et al. Natural history of primary sclerosing cholangitis and prognostic value of Cholangiography in a Dutch population. Gut. 2002; 51: 562–566.
- 73 Ludwig J, LaRusso NF, Wiesner RH. Primary sclerosing cholangitis. In: RL Peters, JG Craig, eds. Contemporary issues in surgical pathology: liver pathology. New York: Churchill Livingstone; 1986: 193–213.
- 74 Zein CO, Lindor KD, Angulo P. Prevalence and predictors of esophageal varices in patients with primary sclerosing cholangitis. Hepatology. 2004; 39: 204–210.
- 75 Kim WR, Therneau TM, Wiesner RH, et al. A revised natural history model for primary sclerosing cholangitis obviates the need for liver histology. Mayo Clinic Proc. 2000; 75: 688–694.
- 76 Bergquist A, Ekbom A, Olsson R, et al. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol. 2002; 36: 321–327.
- 77 Fevery J, Verslype C, Lai G, et al. Incidence, diagnosis, and therapy of cholangiocarcinoma in patients with primary sclerosing cholangitis. Dig Dis Sci. 2007; 52: 3123–3135.
- 78 Boberg KM, Jebsen P, Clausen OP, et al. Diagnostic benefit of biliary brush cytology in cholangiocarcinoma in primary sclerosing cholangitis. J Hepatol. 2006; 45: 568–574.
- 79 Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med. 1997; 336: 691–695.
- 80 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. 2005; 129: 1464–1472.
- 81 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. 2008; 48: 792–800.
- 82 Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009; 50: 808–814.
- 83 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: 89–95.
- 84 Baluyut AR, Sherman S, Lehman GA, et al. Impact of endoscopic therapy on the survival of patients with primary sclerosing cholangitis. Gastrointest Endosc. 2001; 53: 308–312.
- 85 Tischendorf JJ, Meier PN, Strassburg CP, et al. Characterization and clinical course of hepatobiliary carcinoma in patients with primary sclerosing cholangitis. Scand J Gastroenterol. 2006; 41: 1227–1234.
- 86 Rea DJ, Heimbach JK, Rosen CB, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005; 242: 451–458.
- 87 Graziadei IW, Wiesner RH, Marotta PJ, et al. Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis. Hepatology. 1999; 30: 1121–1127.
- 88 Graziadei IW, Wiesner RH, Batts KP, et al. Recurrence of primary sclerosing cholangitis following liver transplantation. Hepatology. 1999; 29: 1050–1056.
- 89 Wee A, Ludwig J, Coffey RJ Jr, et al. Hepatobiliary carcinoma associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hum Pathol. 1985; 16: 719–726.
- 90 Angulo P, Maor-Kendler Y, Lindor KD. Small-duct primary sclerosing cholangitis:prevalence and natural history. Hepatology. 2002; 35: 1494–1500.
- 91 Björnsson E, Boberg KM, Cullen S, et al. Patients with small duct primary sclerosing cholangitis have a favorable long-term prognosis. Gut. 2002; 51: 731–735.
- 92 Broomé U, Glaumann H, Lindstöm E, et al. Natural history and outcome in 32 Swedish patients with small duct primary sclerosing cholangitis (PSC). J Hepatol. 2002; 36: 586–589.
- 93 Björnsson E, Olsson R, Bergquist A, et al. The natural history of small-duct primary sclerosing cholangitis. Gastroenterology. 2008; 134: 975–980.
- 94 Saldeen K, Friman S, Olausson M, et al. Follow-up after liver transplantation for primary sclerosing cholangitis: effects on survival, quality of life, and colitis. Scand J Gastroenterol. 1999; 34: 535–540.
- 95 Befeler AS, Lissoos TW, Schiano TD, et al. Clinical course and management of inflammatory bowel disease after liver transplantation. Transplantation. 1998; 65: 393–396.
- 96 Riley TR, Schoen RE, Lee RG, et al. A case series of transplant recipients who despite immunosuppression developed inflammatory bowel disease. Am J Gastroeneterol. 1997; 92: 279–282.
- 97 Papatheodoridis GV, Hamilton M, Mistry PK, et al. Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis. Gut. 1998; 43: 595–596.
- 98 Verdonk RC, Dijkstra G, Haagsma EB, et al. Inflammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease. Am J Transplant. 2006; 6: 1422–1429.
- 99 Zins BJ, Sandborn WJ, Penna CR, et al. Pouchitis disease course after orthotopic liver transplantation in patients with primary sclerosing cholangitis and an ileal pouch-anal anastomosis. Am J Gastroenterol. 1995; 90: 2177–2180.
- 100 Freeman K, Shao Z, Remzi FH, et al. Impact of orthotopic liver transplant for primary sclerosing cholangitis on chronic antibiotic refractory pouchitis. Clin Gastroenterol Hepatol. 2008; 6: 62–68.
- 101 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. 2008; 95: 882–886.
- 102 Poritz LS, Koltun WA. Surgical management of ulcerative colitis in the presence of primary sclerosing cholangitis. Dis Colon Rectum. 2003; 46: 173–178.
- 103 Cangemi JR, Wiesner RH, Beaver SJ, et al. Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis. Gastroenterology. 1989; 96: 790–794.
- 104 Mikkola K, Kiviluoto T, Riihelä M, et al. Liver involvement and its course in patients operated on for ulcerative colitis. Hepatogastroenterology. 1995; 42: 68–72.
- 105 Lepistö A, Kivistö S, Kivisaari L, et al. Primary sclerosing cholangitis: outcome of patients undergoing restorative proctocolecetomy for ulcerative colitis. Int J Colorectal Dis. 2009; 24: 1169–1174.
- 106 Woodward J, Neuberger J. Autoimmune overlap syndromes. Hepatology. 2001; 33: 994–1002.
- 107 Gregorio GV, Portmann B, Karani J, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology. 2001; 33: 544–553.
- 108 Abdo AA, Bain VG, Kichian K, et al. Evolution of autoimmune hepatitis to primary sclerosing cholangitis: a sequential syndrome. Hepatology. 2002; 36: 1393–1399.
- 109 Floreani A, Rizzotto ER, Ferrara F, et al. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol. 2005; 100: 1516–1522.
- 110 Perdigoto R, Carpenter H, Czaja A. Frequency and significance of chronic ulcerative colitis in severe corticosteroid-treated autoimmune hepatitis. J Heparol. 1992; 14: 325–331.
- 111 Czaja AJ, Carpenter HA. Autoimmune hepatitis with incidental histologic features of bile duct injury. Hepatology. 2001; 34: 659–665.
- 112 de Suray N, Van Beers B, Sempoux C, et al. Autoimmune pancreatitis, sclerosing cholangitis, liver inflammatory pseudotumors, retroperitoneal fibrosis, lymphadenopathy, and sialoadenitis in a single patient: a multifaced expression of a hitherto unrecognized systemic autoimmune syndrome? Pancreas. 2009; 38: 476–478.
- 113 Bjornsson E, Chari ST, Smyrk TC, et al. Immunoglobulin G4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology 2007; 1547–1554.
- 114 Mendes FD, Jorgensen R, Keach J, et al. Elevated serum IgG4 concentration in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2006; 101: 2070–2075.
- 115 Zhang LL, J, Abraham SC, et al. IgG4+ plasma cell infiltrates in liver explants with primary sclerosing cholangitis. Modern Pathol. 2009; 22: 1480.
- 116 Dastis SN, Latinne D, Sempoux C, et al. Ulcerative colitis associated with IgG4 cholangitis: similar features in two HLA identical siblings. J Hepatol. 2009; 51: 601–605.
- 117 Webster GJ, Pereira SP, Chapman RW. Autoimmune pancreatitis/IgG4-associated cholangitis and primary sclerosing cholangitis—overlapping or separate diseases? J Hepatol. 2009; 51: 398–402.
- 118 Keljo DJ, Sugerman KS. Pancreatitis in patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1997; 25: 108–112.
- 119 Weber P, Seibold F, Jenss H. Acute pancreatitis in Crohn's disease. J Clin Gastroenterol. 1993; 17: 286–291.
- 120 Lankish PG, Droge M, Gottesleben F. Drug induced acute pancreatitis: incidence and severity. Gut. 1995; 37: 565–567.
- 121
Deprez P,
Descamps CH,
Fiasse R.
Pancreatitis induced by 5-aminosalicylic acid.
Lancet.
1989;
ii:
445–446.
10.1016/S0140-6736(89)90620-X Google Scholar
- 122 Barthet M, Hastier P, Bernard JP, et al. Chronic pancreatitis and inflammatory bowel disease: true or coincidental association? Am J Gastroenterol. 1999; 94: 2141–2148.
- 123 Herrlinger KR, Stange EF. The pancreas and inflammatory bowel diseases. Int J Pancreatol. 2000; 27: 171–179.
- 124 Altman HS, Philips G, Bank S, et al. Pancreatitis associated with duodenal Crohn's disease. Am J Gastroenterol. 1983; 78: 174–177.
- 125 Legge DA, Hofman HN, Carlson HC. Pancreatitis as a complication of regional enteritis of the duodenum. Gastroenterology. 1971; 61: 834–837.
- 126 Matsumoto T, Matsui T, Iida M, et al. Acute pancreatitis as a complication of Crohn's disease. Am J Gastroenterol. 1989; 84: 804–807.
- 127 Spiess SE, Braun M, Vogelzang RL, et al. Crohn's disease of the duodenum complicated by pancreatitis and common bile duct obstruction. Am J Gastroenterol. 1992; 87: 1033–1036.
- 128 Gschwantler M, Kogelbauer G, Klose W, et al. The pancreas as a site of granulomatous inflammation in Crohn's disease. Gastroenterology. 1995; 108: 1246–1249.
- 129 Kazumori H, Ashizawa N, Moriyama N, et al. Primary sclerosing pancreatitis and cholangitis. Int J Pancreatol. 1998; 24: 123–127.
- 130 Moolsintong P, Loftus EV, Chari ST, et al. Acute pancreatitis in patients with Crohn's disease: clinical features and outcomes. Inflamm Bowel Dis. 2005; 11: 1080–1084.
- 131 Seyrig JA, Jian R, Modigliani R, et al. Idiopathic pancreatitis associated with inflammatory bowel disease. Dig Dis Sci. 1985; 30: 1121–1126.
- 132 Heikius B, Niemela S, Lehtola J, et al. Pancreatic duct abnormalities and pancreatic function in patients with chronic inflammatory bowel disease. Scand J Gastroenterol. 1996; 31: 517–523.
- 133 Katz S, Bank S, Greenberg R, et al. Hyperamylasemia in inflammatory bowel disease. J Clin Gastroenterol. 1988; 6: 627–630.
- 134 Barthet M, Lesavre N, Desplats S, et al. Frequency and characteristics of pancreatitis in patients with inflammatory bowel disease. Pancreatology. 2006; 6: 464–471.
- 135 Ball WP, Baggenstoss AH, Bargen JA. Pancreatic lesions associated with chronic ulcerative colitis. Arch Pathol. 1950; 50: 345–358.
- 136 Rasmussen HH, Fonager K, Sorensen HT, et al. Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. Scand J Gastroenterol. 1999; 34: 199–201.
- 137 Barthet M, Dubucquoy L, Garcia S, et al. Pancreatic changes in TNBS-induced colitis in mice. Gastroenterol Clin Biol. 2003; 27: 895–900.
- 138 Angelini G, Cavallini G, Bovo P, et al. Pancreatic function in chronic inflammatory bowel disease. Int J Pancreatol. 1988; 3: 185–193.
- 139 Hegnhoj J, Hansen CP, Rannem T, et al. Pancreatic function in Crohn's disease. Gut. 1990; 31: 1076–1979.
- 140 Chapin LE, Scudamore HH, Baggenstoss AH, et al. Regional enteritis-associated visceral charges. Gastroenterology. 1956; 30: 404–415.
- 141 Stocker W, Otte M, Ulrich S, et al. Autoimmunity to pancreatic juice in Crohn's disease. Results of an autoantibody screening in patients with chronic inflammatory bowel disease. Scand J Gastroenterol Suppl. 1987; 139: 41–52.
- 142 Targan SR, Landers CJ, Cobb L, et al. Perinuclear anti-neutrophil cytoplasmic antibodies are spontaneously produced by mucosal B cells of ulcerative colitis patients. J Immunol. 1995; 155: 3262–3267.
- 143 Hill GL, Mair WS, Goligher JC. Gallstones after ileostomy and ileal resection. Gut. 1975; 16: 932–936.
- 144 Whorwell PJ, Hawkins R, Dewbury K, et al. Ultrasound survey of gallstones and other hepatobiliary disorders in patients with Crohn's disease. Dig Dis Sci. 1984; 29: 930–933.
- 145 Lorusso D, Leo S, Mossa A, et al. Cholelithiasis in inflammatory bowel disease: a case-control study. Dis Colon Rectum. 1990; 33: 791–794.
- 146 Lapidus A, Bangstad M, Astrom M, et al. The prevalence of gallstone disease in a defined cohort of patients with Crohn's disease. Am J Gastroenterol. 1999; 94: 1261–1266.
- 147 Fraquelli M, Losco A, Visentin S, et al. Gallstone disease and related risk factors in patients with Crohn disease: analysis of 330 consecutive cases. Arch Intern Med. 2001; 161: 2201–2204.
- 148 Bargiggia S, Maconi G, Elli M, et al. Sonographic prevalence of liver steatosis and biliary tract stones in patients with inflammatory bowel disease: study of 511 subjects at a single centre. J Clin Gastroenterol. 2003; 36: 417–420.
- 149 Dowling RH, Bell GD, White J. Lithogenic bile in patients with ileal dysfunction. Gut. 1972; 13: 415–420.
- 150 Lapidus A, Einarsson K. Effects of ileal resection on biliary lipids and bile acid composition in patients with Crohn's disease. Gut. 1991; 32: 1488–1491.
- 151 Lapidus A, Einarsson C. Bile composition in patients with ileal resection due to Crohn's disease. Inflamm Bowel Dis. 1998; 4: 89–94.
- 152 Brink MA, Slors JFM, Keulemans YCA, et al. Enterohepatic cycling of bilirubin: a putative mechanism for pigment gallstone formation in ileal Crohn's disease. Gastroenterology. 1999; 116: 1420–1427.
- 153 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: 1267–1274.
- 154 Damiao AO, Sipahl AM, Vezozzo DP, et al. Gallbladder hypokinesis in Crohn's disease. Digestion. 1997; 58: 458–463.
- 155 Annese V, Vantrappen G. Gallstones in Crohn's disease: another hypothesis. Gut. 1994; 35: 1676.
- 156 Pitt HA, King W, Mann L, et al. Increased risk of cholelithiasis with prolonged total parenteral nutrition. Am J Surg. 1983; 145: 106–112.
- 157 Jackson LM, O'Gorman PJ, O'Connell J, et al. Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden. QJM. 1997; 90: 183–188.
- 158 Miehsler W, Reinisch W, Valic E, et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut. 2004; 53: 542–548.
- 159 Liappis AP, Roberts AD, Schwartz AM, et al. Thrombosis and infection: a case of transient anti-cardiolipin antibody associated with pylephlebitis. Am J Med Sci. 2003; 325: 365–368.
- 160 Sanghavi P, Paramesh A, Dwivedi A, et al. Mesenteric Arterial Thrombosis as a complication of Crohn's disease. Dig Dis Sci. 2001; 46: 2344–2346.
- 161 Vakil N, Hayne G, Sharma A, et al. Liver abscess in Crohn's disease. Am J Gastroenterol. 1994; 89: 1090–1095.
- 162 Margalit M, Elinav H, Ilan Y, et al. Liver abscess in inflammatory bowel disease: Report of two cases and review of the literature. J Gastroenterol Hepatol. 2004; 19: 1338–1342.
- 163 Hazzan D, Fishman E, Heller E, et al. Liver abscess in Crohn's disease: a report of three cases. Mount Sinai J Med. 2004; 71: 351–355.
- 164 Plemmons RM, Dooley DP, Longfield RN. Septic thrombophlebitis of the portal vein (Pylephlebitis): diagnosis and management in the modern era. Clin Infec Dis. 1995; 21: 1114–1120.
- 165 Baker ME, Remzi F, Einstein D, et al. CT depiction of portal vein thrombi after creation of ileal pouch-anal anastomosis. Radiology. 2003; 227: 73–79.
- 166 Remzi FH, Fazio VW, Oncel M, et al. Portal vein thrombi after restorative proctocolectomy. Surgery. 2002; 132: 655–661.
- 167 Ball CG, MacLean AR, Buie WD, et al. Portal vein thrombi after ileal pouch-anal anastomosis: its incidence and association with pouchitis. Surg Today. 2007; 37: 552–557.
- 168 Present DH, Meltzer SJ, Krumholz MP, et al. 6-Mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity. Ann Intern Med. 1989; 111: 641–649.
- 169 Tiede I, Fritz G, Strand S, et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+T lymphocytes. J Clin Invest. 2003; 111: 1133–1145.
- 170 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: 1106–1114.
- 171 Romagnuolo J, Sadowski DC, Lalor E, et al. Cholestatic hepatocellular injury with azathioprine: a case report and review of the mechanisms of hepatotoxicity. Can J Gastroenterol. 1998; 12: 479–483.
- 172 Bouchnik Y, Lemann M, Mary J-Y, et al. Long-term followup of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. Lancet. 1996; 347: 215–219.
- 173 Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut. 2002; 50: 485–489.
- 174 Shorey J, Schenker S, Suki WN, et al. Hepatotoxicity of mercaptopurine. Arch Intern Med. 1968; 122: 54–58.
- 175 Dubinsky MC, Yang HY, Hassard PV, et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology. 2002; 122: 904–915.
- 176 Cuffari C, Hunt S, Bayless T. Utilization of erythrocyte 6-thioguanine metabolite levels to optimize azathioprine therapy in patients with inflammatory bowel disease. Gut. 2001; 48: 642–646.
- 177 Cuffari C, Theoret Y, Latour S, et al. 6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity. Gut. 1996; 39: 401–406.
- 178 Colombel JF, Ferrari N, Debuysere H, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000; 118: 1025–1030.
- 179 Shaye OA, Yadegari M, Abreu MT, et al. Hepatotoxicity of 6-mercaptopurine (6-MP) and azathioprine (AZA) in adult IBD patients. Am J Gastroenterol. 2007; 102: 2488–2494.
- 180 Lichtenstein GR, Abreu MT, Cohen R, et al; American Gastroenterological Association. American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology. 2006; 130: 935–939.
- 181 Farrell GC. Drug-induced liver disease, 1st ed. Singapore: Churchill Livingstone; 1994.
- 182 DeLeve LD, Wang X, Kuhlenkamp JF, et al. Toxicity of azathioprine and monocrotaline in murine sinusoidal endothelial cells and hepatocytes: the role of glutathione and relevance to hepatic venoocclusive disease. Hepatology. 1996; 23: 589–599.
- 183 Russmann S, Zimmermann A, Krahenbuhl S, et al. Venoocclusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis. Eur J Gastroenterol Hepatol. 2001; 13: 287–290.
- 184 Daniel F, Cadranel JF, Seksik P, et al. Azathioprine-induced nodular regenerative hyperplasia in IBD patients. Gastroenterol Clin Biol. 2005; 29: 600–603.
- 185 Bertino J. The mechanism of action of the folate antagonists in man. Cancer Res. 1963; 23: 1286.
- 186 Alarcon GS, Goodman TA, Polisson RP. Methotrexate: adverse reactions and major toxicities. Rheumatic Dis Clin North Am. 1994; 20: 513–528.
- 187 Kremer JM, Alarcon GS, Lightfoot RW Jr, et al. Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. Arthritis Rheum. 1994; 37: 316–328.
- 188 Kremer JM, Galivan J, Streckfuss A, et al. Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Association with hepatic folate deficiency and formation of polyglutamates. Arthritis Rheum. 1986; 29: 832–835.
- 189 Sandborn WJ. A review of immunemodifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol. 1996; 91: 423–433.
- 190 Feagan BG, Rochon J, Fedorak RN, et al. Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. N Engl J Med. 1995; 332: 292–297.
- 191 Kozarek RA, Bredfeldt JE, Rosoff LE, et al. Does chronic methotrexate (MTX) cause liver toxicity when used for refractory inflammatory bowel disease (IBD)? Gastroenterology. 1991; 100: A221 (Abstract).
- 192 Te HS, Schiano TD, Kuan SF, et al. Hepatic effects of long term methotrexate use in the treatment of inflammatory bowel disease. Am J Gastroenterol. 2000; 95: 3150–3156.
- 193 Wahed M, Louis-Auguste JR, Baxter LM, et al. Efficacy of methotrexate in Crohn's disease and ulcerative colitis patients unresponsive or intolerant to azathioprine/mercaptopurine. Aliment Pharmacol Ther. 2009; 30: 614–620.
- 194 Roenigk HH Jr, Auerbach R, Mailbach H, et al. Methotrexate in psoriasis: consensus conference. J Am Acad Dermatol. 1998; 38: 478–485.
- 195 Taffet SL, Das KM. Sulfasalazine: adverse effects and desensitization. Dig Dis Sci. 1983; 28: 833–842.
- 196 Hanauer SB, Meyers S, Sachar DB. The pharmacology of anti-inflammatory drugs in inflammatory bowel disease. In: JB Kirsner, RG Shorter, editors. Inflammatory bowel disease, 4th ed. Baltimore: Williams & Wilkins; 1995; 643–663.
- 197 Teo L, Tan E. Sulphasalazine-induced DRESS. Singapore Med J. 2006; 47: 237–239.
- 198 Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomized trial. BMJ. 1989; 298: 82–86.
- 199 Hautekeete ML, Bourgeois N, Potvin P, et al. Hypersensitivity with hepatotoxicity to mesalazine after hypersensitivity to sulfasalazine. Gastroenterology. 1992; 103: 1925–1927.
- 200 Stochus B, Meybehm M, Spengler U, et al. Cholestasis associated with mesalazine therapy in a patient with Crohn's disease. J Hepatol. 1997; 26: 425–428.
- 201 Deltenre P, Berson A, Marcellin P, et al. Mesalazine (5-aminosalicylic acid) induced chronic hepatitis. Gut. 1999; 44: 886–888.
- 202 Nahon S, Cadranel JF, Chazouilleres O, et al. Liver and inflammatory bowel disease. Gastroenterol Clin Biol. 2009; 33: 370–381.
- 203 Stacey NH, Kotecka B. Inhibition of taurocholate and ouabain transport in isolated rat hepatocytes by cyclosporin A. Gastroenterology. 1988; 95: 780–786.
- 204 Parrott NR, Taylor RM, Venables CW, et al. Treatment of Crohn's disease in relapse with cyclosporin A. Br J Surg. 1988; 75: 1185–1188.
- 205 Arts J, D'Haens G, Zeegers M, et al. Long-term outcome of treatment with intravenous cyclosporin in patients with severe ulcerative colitis. Inflamm Bowel Dis. 2004; 10: 73–78.
- 206 Germano V, Picchianti Diamanti A, Baccano G, et al. Autoimmune hepatitis associated with infliximab in a patient with psoriatic arthritis. Ann Rheum Dis. 2005; 64: 1519–1520.
- 207 Schiemann U, Kellner H. Gastrointestinal side effects in the therapy of rheumatologic diseases. Z Gastroenterol. 2002; 40: 937–943.
- 208 Mastroianni A, Minutilli E, Mussi A, et al. Cytokine profiles during infliximab monotherapy in psoriatic arthritis. Br J Dermatol. 2005; 153: 531–536.
- 209 Menghini V. Amindra S. Infliximab associated reversible cholestatic liver disease. Mayo Clin Proc. 2001; 76: 84–86.
- 210 Tobon GJ, Canas C, Jaller JJ, et al. Serious liver disease induced by infliximab. Clin Rheumatol. 2006; 26: 578–581.
- 211 Ierardi E, Valle ND, Nacchiero MC, et al. Onset of liver damage after a single administration of infliximab in a patient with refractory ulcerative colitis. Clin Drug Investig. 2006; 26: 673–676.
- 212 Jarret S, Cunnane G, Conaghan P, et al. Anti-tumor necrosis factor therapy-induced vasculitis: case series. J Rheumatol. 2003; 30: 2287–2291.
- 213 Jarnerot G, Hertervig E, Friis-Liby I, et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005; 128: 1805–1811.
- 214 Biancone L, Pavia M, Del Vecchio Blanco G, et al. Hepatitis B and C virus infection in Crohn's disease. Inflamm Bowel Dis. 2001; 7: 287–294.
- 215 Ueno Y, Tanaka S, Shimamoto M, et al. Infliximab therapy for Crohn's disease in a patient with chronic hepatitis B. Digest Dis Sci. 2005; 50: 163–166.
- 216 Esteve M, Saro C, Gonzalez-Huix F, et al. Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis. Gut. 2004; 53: 1363–1365.
- 217 Guidotti LG, Chisari FV. Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol. 2001; 19: 65–91.
- 218 Herbein G, O'Brien WA. Tumor necrosis factor (TNF)-alpha and TNF receptors in viral pathogenesis. Proc Soc Exp Biol Med. 2000; 223: 241–257.
- 219 Papa A, Mocci G, Bonizzi M, et al. Use of infliximab in particular clinical settings: management based on current evidence. Am J Gastroenterol. 2009; 104: 1575–1586.
- 220 Ferri C, Ferraccioli G, Ferrari D, et al. Safety of anti-tumor necrosis factor alpha therapy in patients with rheumatoid arthritis and chronic hepatitis C virus infection. J Rheumatol. 2008; 35: 1944–1949.
- 221 Nathan DM, Angus PW, Gibson PR. Hepatitis B and C virus infections and anti-tumor necrosis factor-alpha therapy: guidelines for clinical approach. J Gastroenterol Hepatol. 2006; 21: 1366–1371.
- 222 Bajaj JS, Saeian K, Varma RR, et al. Increased rates of early adverse reaction to azathioprine in patients with Crohn's disease compared to autoimmune hepatitis: a tertiary referral center experience. Am J Gastroenterol. 2005; 100: 1121–1125.
- 223
Villarreal HA,
Wells LD,
Neusschwander-Tetri BA,
Azathioprine induced acute pancreatitis in mice.
Gastroenterolgy.
1995;
108(
suppl):
A398.
10.1016/0016-5085(95)24249-X Google Scholar
- 224 Mardini HE. Azathioprine-induced pancreatitis in Crohn's disease: a smoking gun or guilt by association. Aliment Pharmacol Ther. 2005; 15; 21: 195.
- 225 Alexander S, Dowling D. Azathioprine pancreatitis in inflammatory bowel disease and successful subsequent treatment with mercaptopurine. Intern Med J. 2005; 35: 570–571.
- 226 Lamers CBHW, Griffioen G, van Hegezand RA, et al. Azathioprine: an update on clinical efficacy and safety in inflammatory bowel disease. Scand J Gastroenterol. 1999; S230: 111–115.
- 227 Sturdevant RA, Singleton JW, Deren JL, et al. Azathioprine-related pancreatitis in patients with Crohn's disease. Gastroenterology. 1979; 77( 4 Pt 2): 883–886.
- 228 Siegel CA, Marden SM, Persing SM, et al. Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's disease: a meta-analysis. Clin Gastroenterol Hepatol. 2009; 7: 874–881.
- 229 Mackey AC, Green L, Liang LC, et al. Hepatosplenic T-cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007; 44: 265–267.
- 230 Navarro JT, Ribera JM, Mate JL, et al. Hepatosplenic T-gammadelta lymphoma in a patient with Crohn's disease treated with azathioprine. Leuk Lymphoma. 2003; 44: 531–533.
- 231 Mittal S, Milner BJ, Johnston PW, et al. A case of hepatosplenic gamma-delta T-cell lymphoma with a transient response to fludarabine and alemtuzumab. Eur J Haematol. 2006; 76: 531–534.
- 232 Keller KM. Hepatosplenic T-cell lymphoma in a 15-year old boy with ulcerative colitis treated with azathioprine for 9 years. J Pediatr Gastroenterol Nutr. 2007; 44: e259.
- 233 Shale M, Kanfer E, Panaccione R, et al. Hepatosplenic T cell lymphoma in inflammatory bowel disease. Gut. 2008; 57: 1639–1641.
- 234 Tey SK, Marlton PV, Hawley CM, et al. Post-transplant hepatosplenic T-cell lymphoma successfully treated with Hyper CVAD regimen. Am J Hematol. 2008; 83: 330–333.
- 235 Konuma T, Ooi J, Takahashi S, et al. Allogeneic stem cell transplantation for hepatosplenic gammadelta T-cell lymphoma. Leuk Lymphoma. 2007; 48: 630–632.
- 236http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm175843.htm
- 237 Grandval PH, Barthet M, Gargia S, et al. Pseudotumorous chronic pancreatitis associated with inflammatory bowel disease. Dig Dis Sci. 2001; 46: 898–900.
- 238 Sahel J, Barthet M, Gasmi M. Autoimmune pancreatitis: increasing evidence for a clinical entity with various patterns. Eur J Gastroenterol Hepatol. 2004; 16: 1265–1268.
- 239 Ravi K, Chari ST, Vege SS, et al. Inflammatory bowel disease in the setting of autoimmune pancreatitis. Inflamm Bowel Dis. 2009; 15: 1326–1330.
- 240 Xiao WB, Liu YL. Primary biliary cirrhosis and ulcerative colitis: a case report and review of literature. World J Gastroenterol. 2003; 9: 878–880.
- 241 Koulentaki M, Koutroubakis IE, Petinaki E, et al. Ulcerative colitis associated with primary biliary cirrhosis. Dig Dis Sci. 1999; 44: 1953–1956.
- 242 Lever E, Balasubramanian K, Condon S, et al. Primary biliary cirrhosis associated with ulcerative colitis. Am J Gastroenterol. 1993; 88: 945–947.
- 243 Riegler G, D'Inca R, Sturniolo GC, et al. Hepatobiliary alterations in patients with inflammatory bowel disease: a multicenter study. Scand J Gastroenterol. 1998; 33: 93–98.
- 244 de Dombal FT, Goldie W, Watts JMcK, Goligher JC. Hepatic histological changes in ulcerative colitis. Scand J Gastroenterol. 1966; 1: 220–227.
- 245 Greenstein AJ, Sachar DB, Panday AK, et al. Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients. Medicine (Baltimore). 1992; 71: 261–270.
- 246 Wester AL, Vatn MH, Fausa O. Secondary amyloidosis in inflammatory bowel disease: a study of 18 patients admitted to Rikshospitalet University Hospital, Oslo, from 1962 to 1998. Inflamm Bowel Dis. 2001; 7: 295–300.
- 247 Callen JP, Soderstrom RM. Granulomatous hepatitis associated with salicylazosulfapyridine therapy. South Med J. 1978; 71: 1159–1160.
- 248 Charatcharoenwitthaya P, Lindor KD. Primary sclerosing cholangitis: patients with a rising alkaline phosphatase at annual follow-up. Clin Gastroenterol Hepatol. 2007; 5: 32–36.
