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Published in: BMC Gastroenterology 1/2019

Open Access 01-12-2019 | Azathioprine | Research article

Hepatobiliary and pancreatic manifestations in inflammatory bowel diseases: a referral center study

Authors: Fotios S. Fousekis, Konstantinos H. Katsanos, Vasileios I. Theopistos, Gerasimos Baltayiannis, Maria Kosmidou, Georgios Glantzounis, Leonidas Christou, Epameinondas V. Tsianos, Dimitrios K. Christodoulou

Published in: BMC Gastroenterology | Issue 1/2019

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Abstract

Background

Hepatobiliary and pancreatic manifestations have been reported in patients with Crohn’s disease or ulcerative colitis. Our aim was to describe the prevalence of hepatobiliary and pancreatic manifestations in inflammatory bowel disease and their association with the disease itself and the medications used.

Methods

Data were retrospectively extracted from the clinical records of patients followed up at our tertiary IBD referral Center.

Results

Our study included 602 IBD patients, with liver function tests at regular intervals. The mean follow-up was 5.8 years (Std. Dev.: 6.72). Abdominal imaging examinations were present in 220 patients and revealed findings from the liver, biliary tract and pancreas in 55% of examined patients (120/220). The most frequent findings or manifestations from the liver, biliary tract and pancreas were fatty liver (20%, 44/220), cholelithiasis (14.5%, 32/220) and acute pancreatitis (0.6%, 4/602), respectively. There were 7 patients with primary sclerosing cholangitis. Regarding hepatitis viruses, one-third of the patients had been tested for hepatitis B and C. 5% (12/225) of them had positive hepatitis B surface antigen and 13.4% had past infection with hepatitis B virus (positive anti-HBcore). In addition, most of the patients were not immune against hepatitis B (negative anti-HBs), while 3% of patients were anti-HCV positive and only one patient had active hepatitis C. Furthermore, 24 patients had drug-related side effects from the liver and pancreas. The side effects included 21 cases of hepatotoxicity and 3 cases of acute pancreatitis. Moreover, there were two cases of HBV reactivation and one case of chronic hepatitis C, which were successfully treated.

Conclusion

In our study, approximately one out of four patients had some kind by a hepatobiliary or pancreatic manifestation. Therefore, it is essential to monitor liver function at regular intervals and differential diagnosis should range from benign diseases and various drug related side effects to severe disorders, such as primary sclerosing cholangitis.
Literature
1.
go back to reference Wang R, Leong RW. Primary sclerosing cholangitis as an independent risk factor for colorectal cancer in the context of inflammatory bowel disease: a review of the literature. World J Gastroenterol. 2014;20(27):8783–9.PubMedPubMedCentral Wang R, Leong RW. Primary sclerosing cholangitis as an independent risk factor for colorectal cancer in the context of inflammatory bowel disease: a review of the literature. World J Gastroenterol. 2014;20(27):8783–9.PubMedPubMedCentral
2.
go back to reference Claessen MM, Vieggaar FP, Tytgat KM, Siersema PD, van Buuren HR. High lifetime risk of cancer in primary sclerosing cholangitis. J Hepatol. 2009;50(1):158–64.CrossRef Claessen MM, Vieggaar FP, Tytgat KM, Siersema PD, van Buuren HR. High lifetime risk of cancer in primary sclerosing cholangitis. J Hepatol. 2009;50(1):158–64.CrossRef
3.
go back to reference Gizard E, Ford AC, Bronowicki JP, Peyrin-Biroulet L. Systematic review: the epidemiology of the hepatobiliary manifestations in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2014;40(1):3–15.CrossRef Gizard E, Ford AC, Bronowicki JP, Peyrin-Biroulet L. Systematic review: the epidemiology of the hepatobiliary manifestations in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2014;40(1):3–15.CrossRef
4.
go back to reference Parente F, Pastore L, Bargiggia S, Cucino C, Greco S, Molteni M, et al. Incidence and risk factors for gallstones in patients with inflammatory bowel disease: a large case-control study. Hepatology. 2007;45(5):1267–74.CrossRef Parente F, Pastore L, Bargiggia S, Cucino C, Greco S, Molteni M, et al. Incidence and risk factors for gallstones in patients with inflammatory bowel disease: a large case-control study. Hepatology. 2007;45(5):1267–74.CrossRef
5.
go back to reference Bargiggia S, Maconi G, Elli M, Molteni P, Ardizzone S, Parente F, et al. Sonographic prevalence of liver steatosis and biliary tract stones in patients with inflammatory bowel disease: study of 511 subjects at a single center. J Clin Gastroenterol. 2003;36(5):417–20.CrossRef Bargiggia S, Maconi G, Elli M, Molteni P, Ardizzone S, Parente F, et al. Sonographic prevalence of liver steatosis and biliary tract stones in patients with inflammatory bowel disease: study of 511 subjects at a single center. J Clin Gastroenterol. 2003;36(5):417–20.CrossRef
6.
go back to reference Sourianarayanane A, Garg G, Smith TH, Butt MI, McCullough AJ, Shen B. Risk factors of non-alcoholic fatty liver disease in patients with inflammatory bowel disease. J Crohns Colitis. 2013;7(8):e279–85.CrossRef Sourianarayanane A, Garg G, Smith TH, Butt MI, McCullough AJ, Shen B. Risk factors of non-alcoholic fatty liver disease in patients with inflammatory bowel disease. J Crohns Colitis. 2013;7(8):e279–85.CrossRef
7.
go back to reference 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(4):987–93.CrossRef 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(4):987–93.CrossRef
8.
go back to reference Koulentaki M, Koutroubakis IE, Petinaki E, Tzardi M, Oekonomaki H, Mouzas I, et al. Ulcerative colitis associated with primary biliary cirrhosis. Dig Dis Sci. 1999;44(10):1953–6.CrossRef Koulentaki M, Koutroubakis IE, Petinaki E, Tzardi M, Oekonomaki H, Mouzas I, et al. Ulcerative colitis associated with primary biliary cirrhosis. Dig Dis Sci. 1999;44(10):1953–6.CrossRef
9.
go back to reference Ransford RA, Langman MJ. Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut. 2002;51(4):536–9.CrossRef Ransford RA, Langman MJ. Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut. 2002;51(4):536–9.CrossRef
10.
go back to reference Khan N, Abbas AM, Whang N, Balart LA, Bazzano LA, Kelly TN. Incidence of liver toxicity in inflammatory bowel disease patients treated with methotrexate: a meta-analysis of clinical trials. Inflamm Bowel Dis. 2012;18(2):359–67.CrossRef Khan N, Abbas AM, Whang N, Balart LA, Bazzano LA, Kelly TN. Incidence of liver toxicity in inflammatory bowel disease patients treated with methotrexate: a meta-analysis of clinical trials. Inflamm Bowel Dis. 2012;18(2):359–67.CrossRef
11.
go back to reference Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut. 2002;50(4):485–9.CrossRef Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut. 2002;50(4):485–9.CrossRef
12.
go back to reference Chaparro M, Ordas I, Cabre E, Garcia-Sanchez V, Bastida G, Penalva M, et al. Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients. Inflamm Bowel Dis. 2013;19(7):1404–10.CrossRef Chaparro M, Ordas I, Cabre E, Garcia-Sanchez V, Bastida G, Penalva M, et al. Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients. Inflamm Bowel Dis. 2013;19(7):1404–10.CrossRef
13.
go back to reference Shelton E, Chaudrey K, Sauk J, Khalili H, Masia R, Nguyen DD, et al. New onset idiosyncratic liver enzyme elevations with biological therapy in inflammatory bowel disease. Aliment Pharmacol Ther. 2015. May;41(10):972–9.CrossRef Shelton E, Chaudrey K, Sauk J, Khalili H, Masia R, Nguyen DD, et al. New onset idiosyncratic liver enzyme elevations with biological therapy in inflammatory bowel disease. Aliment Pharmacol Ther. 2015. May;41(10):972–9.CrossRef
14.
go back to reference Rahier JF, Ben-Horin S, Chowers Y, Conlon C, De Munter P, D'Haens G, et al. European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2009;3(2):47–91.CrossRef Rahier JF, Ben-Horin S, Chowers Y, Conlon C, De Munter P, D'Haens G, et al. European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2009;3(2):47–91.CrossRef
15.
go back to reference Pitchumoni CS, Rubin A, Das K. Pancreatitis in inflammatory bowel diseases. J Clin Gastroenterol. 2010;44(4):246–53.CrossRef Pitchumoni CS, Rubin A, Das K. Pancreatitis in inflammatory bowel diseases. J Clin Gastroenterol. 2010;44(4):246–53.CrossRef
16.
go back to reference Douros A, Bronder E, Andersohn F, Klimpel A, Thomae M, Ockenga J, et al. Drug-induced acute pancreatitis: results from the hospital-based Berlin case-control surveillance study of 102 cases. Aliment Pharmacol Ther. 2013;38(7):825–34.CrossRef Douros A, Bronder E, Andersohn F, Klimpel A, Thomae M, Ockenga J, et al. Drug-induced acute pancreatitis: results from the hospital-based Berlin case-control surveillance study of 102 cases. Aliment Pharmacol Ther. 2013;38(7):825–34.CrossRef
17.
go back to reference Matsumoto T, Yamasaki S, Arakawa A, Abe K, Abe H, Kon K, et al. Exposure to a high total dosage of glucocorticoids produces non-alcoholic steatohepatits. Pathol Int. 2007;57(6):388–9.CrossRef Matsumoto T, Yamasaki S, Arakawa A, Abe K, Abe H, Kon K, et al. Exposure to a high total dosage of glucocorticoids produces non-alcoholic steatohepatits. Pathol Int. 2007;57(6):388–9.CrossRef
18.
go back to reference Tsaitas C, Semertzidou A, Sinakos E. Update on inflammatory bowel disease in patients with primary sclerosing cholangitis. World J Hepatol. 2014;6(4):178–87.CrossRef Tsaitas C, Semertzidou A, Sinakos E. Update on inflammatory bowel disease in patients with primary sclerosing cholangitis. World J Hepatol. 2014;6(4):178–87.CrossRef
19.
go back to reference Toy E, Balasubramanian S, Selmi C, Li CS, Bowlus CL. The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population. BMC Gastroenterol. 2011;11:83.CrossRef Toy E, Balasubramanian S, Selmi C, Li CS, Bowlus CL. The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population. BMC Gastroenterol. 2011;11:83.CrossRef
20.
go back to reference Vazquez-Elizondo G, Mucino-Bermejo J, Mendez-Sanchez N. Gallbladder disease in patients with primary sclerosing cholangitis. Ann Hepatol. 2008;7(2):182–3.PubMed Vazquez-Elizondo G, Mucino-Bermejo J, Mendez-Sanchez N. Gallbladder disease in patients with primary sclerosing cholangitis. Ann Hepatol. 2008;7(2):182–3.PubMed
21.
go back to reference Bermejo F, Lopez-Sanroman A, Taxonera C, Gisbert JP, Perez-Calle JL, Vera I, et al. Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis. Aliment Pharmacol Ther. 2008;28(5):623–8.CrossRef Bermejo F, Lopez-Sanroman A, Taxonera C, Gisbert JP, Perez-Calle JL, Vera I, et al. Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis. Aliment Pharmacol Ther. 2008;28(5):623–8.CrossRef
22.
go back to reference Rasmussen HH, Fonager K, Sorensen HT, Pedersen L, Dahlerup JF, Steffensen FH. Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. A Danish 16-year nationwide follow-up study. Scand J Gastroenterol. 1999;34(2):199–201.CrossRef Rasmussen HH, Fonager K, Sorensen HT, Pedersen L, Dahlerup JF, Steffensen FH. Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. A Danish 16-year nationwide follow-up study. Scand J Gastroenterol. 1999;34(2):199–201.CrossRef
23.
go back to reference Weber P, Seibold F, Jenss H. Acute pancreatitis in Crohn's disease. J Clin Gastroenterol. 1993;17(4):286–91.CrossRef Weber P, Seibold F, Jenss H. Acute pancreatitis in Crohn's disease. J Clin Gastroenterol. 1993;17(4):286–91.CrossRef
24.
go back to reference Loras C, Saro C, Gonzalez-Huix F, Minguez M, Merino O, Gisbert JP, et al. Prevalence and factors related to hepatitis B and C in inflammatory bowel disease patients in Spain: a nationwide, multicenter study. Am J Gastroenterol. 2009;104(1):57–63.CrossRef Loras C, Saro C, Gonzalez-Huix F, Minguez M, Merino O, Gisbert JP, et al. Prevalence and factors related to hepatitis B and C in inflammatory bowel disease patients in Spain: a nationwide, multicenter study. Am J Gastroenterol. 2009;104(1):57–63.CrossRef
25.
go back to reference Ben Musa R, Gampa A, Basu S, Keshavarzian A, Swanson G, Brown M, et al. Hepatitis B vaccination in patients with inflammatory bowel disease. World J Gastroenterol. 2014;20(41):15358–66.CrossRef Ben Musa R, Gampa A, Basu S, Keshavarzian A, Swanson G, Brown M, et al. Hepatitis B vaccination in patients with inflammatory bowel disease. World J Gastroenterol. 2014;20(41):15358–66.CrossRef
26.
go back to reference Vida Perez L, Gomez Camacho F, Garcia Sanchez V, Iglesias Flores EM, Castillo Molina L, Cerezo Ruiz A, et al. Adequate rate of response to hepatitis B virus vaccination in patients with inflammatory bowel disease. Med Clin (Barc). 2009;132(9):331–5.CrossRef Vida Perez L, Gomez Camacho F, Garcia Sanchez V, Iglesias Flores EM, Castillo Molina L, Cerezo Ruiz A, et al. Adequate rate of response to hepatitis B virus vaccination in patients with inflammatory bowel disease. Med Clin (Barc). 2009;132(9):331–5.CrossRef
27.
go back to reference Gisbert JP, Villagrasa JR, Rodriguez-Nogueiras A, Chaparro M. Kinetics of anti-hepatitis B surface antigen titers after hepatitis B vaccination in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(3):554–8.CrossRef Gisbert JP, Villagrasa JR, Rodriguez-Nogueiras A, Chaparro M. Kinetics of anti-hepatitis B surface antigen titers after hepatitis B vaccination in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(3):554–8.CrossRef
28.
go back to reference Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, et al. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370–98.CrossRef Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, et al. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370–98.CrossRef
29.
go back to reference Loras C, Gisbert JP, Saro MC, Piqueras M, Sanchez-Montes C, Barrio J, et al. Impact of surveillance of hepatitis b and hepatitis c in patients with inflammatory bowel disease under anti-TNF therapies: multicenter prospective observational study (REPENTINA 3). J Crohns Colitis. 2014;8(11):1529–38.CrossRef Loras C, Gisbert JP, Saro MC, Piqueras M, Sanchez-Montes C, Barrio J, et al. Impact of surveillance of hepatitis b and hepatitis c in patients with inflammatory bowel disease under anti-TNF therapies: multicenter prospective observational study (REPENTINA 3). J Crohns Colitis. 2014;8(11):1529–38.CrossRef
30.
go back to reference Loras C, Gisbert JP, Minguez M, Merino O, Bujanda L, Saro C, et al. Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy. Gut. 2010;59(10):1340–6.CrossRef Loras C, Gisbert JP, Minguez M, Merino O, Bujanda L, Saro C, et al. Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy. Gut. 2010;59(10):1340–6.CrossRef
31.
go back to reference Gisbert JP, Gonzalez-Lama Y, Mate J. Thiopurine-induced liver injury in patients with inflammatory bowel disease: a systematic review. Am J Gastroenterol. 2007;102(7):1518–27.CrossRef Gisbert JP, Gonzalez-Lama Y, Mate J. Thiopurine-induced liver injury in patients with inflammatory bowel disease: a systematic review. Am J Gastroenterol. 2007;102(7):1518–27.CrossRef
32.
go back to reference de Jong DJ, Derijks LJ, Naber AH, Hooymans PM, Mulder CJ. Safety of thiopurines in the treatment of inflammatory bowel disease. Scand J Gastroenterol Suppl. 2003;(239):69–72. de Jong DJ, Derijks LJ, Naber AH, Hooymans PM, Mulder CJ. Safety of thiopurines in the treatment of inflammatory bowel disease. Scand J Gastroenterol Suppl. 2003;(239):69–72.
Metadata
Title
Hepatobiliary and pancreatic manifestations in inflammatory bowel diseases: a referral center study
Authors
Fotios S. Fousekis
Konstantinos H. Katsanos
Vasileios I. Theopistos
Gerasimos Baltayiannis
Maria Kosmidou
Georgios Glantzounis
Leonidas Christou
Epameinondas V. Tsianos
Dimitrios K. Christodoulou
Publication date
01-12-2019

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