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Liver Disease in Pediatric Inflammatory Bowel Disease

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Pediatric Inflammatory Bowel Disease

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Abstract

Hepatobiliary diseases are among the most common extraintestinal manifestations of inflammatory bowel disease (IBD). These include immune-mediated liver diseases, namely, primary sclerosing cholangitis, autoimmune hepatitis, and an overlap condition between the two, termed autoimmune sclerosing cholangitis. More recently, an additional entity that likely shares an immunological basis, known as IgG4-associated cholangitis (IAC), has been defined and observed to also occur in association with IBD. A number of hepatobiliary manifestations can result from the adverse effects of medications used to treat pediatric IBD, such as methotrexate, thiopurines, and anti-tumor necrosis factor-α antibodies. Another category of hepatobiliary involvement is that which reflects the pathophysiology of IBD, such as cholelithiasis. Abnormal liver biochemistry is common in children with IBD. While often transient and of little consequence, such abnormalities may occasionally herald serious underlying liver disease or medication toxicity. The challenge lies in determining which patients warrant further investigation and intervention versus simple observation. This chapter strives to facilitate this task by providing an overview of and suggesting clinical approaches to various hepatobiliary conditions associated with pediatric IBD.

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References

  1. Navaneethan U, Shen B. Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease. Inflamm Bowel Dis. 2010;16(9):1598–619.

    PubMed  Google Scholar 

  2. Gisbert JP, Luna M, Gonzalez-Lama Y, Pousa ID, Velasco M, Moreno-Otero R, et al. Liver injury in inflammatory bowel disease: long-term follow-up study of 786 patients. Inflamm Bowel Dis. 2007;13(9):1106–14.

    PubMed  Google Scholar 

  3. Mendes FD, Levy C, Enders FB, Loftus EV Jr, Angulo P, Lindor KD. Abnormal hepatic biochemistries in patients with inflammatory bowel disease. Am J Gastroenterol. 2007;102(2):344–50.

    PubMed  Google Scholar 

  4. Yamamoto-Furusho JKS-OM, Uribe M. Prevalence and factors associated with the presence of abnormal function liver tests in patients with ulcerative colitis. Ann Hepatol. 2010;9:397–401.

    PubMed  Google Scholar 

  5. Nemeth A, Ejderhamn J, Glaumann H, Strandvik B. Liver damage in juvenile inflammatory bowel disease. Liver. 1990;10(4):239–48.

    CAS  PubMed  Google Scholar 

  6. Pusateri AJ, Kim SC, Dotson JL, Balint JP, Potter CJ, Boyle BM, et al. Incidence, pattern, and etiology of elevated liver enzymes in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2015;60(5):592–7.

    CAS  PubMed  Google Scholar 

  7. Valentino PL, Feldman BM, Walters TD, Griffiths AM, Ling SC, Pullenayegum EM, et al. Abnormal liver biochemistry is common in pediatric inflammatory bowel disease: prevalence and associations. Inflamm Bowel Dis. 2015;21(12):2848–56.

    PubMed  Google Scholar 

  8. Hyams J, Markowitz J, Treem W, Davis P, Grancher K, Daum F. Characterization of hepatic abnormalities in children with inflammatory bowel disease. Inflamm Bowel Dis. 1995;1(1):27–33.

    CAS  PubMed  Google Scholar 

  9. Goyal A, Hyams JS, Lerer T, Leleiko NS, Otley AR, Griffiths AM, et al. Liver enzyme elevations within 3 months of diagnosis of inflammatory bowel disease and likelihood of liver disease. J Pediatr Gastroenterol Nutr. 2014;59(3):321–3.

    CAS  PubMed  Google Scholar 

  10. Riegler G, D'Inca R, Sturniolo GC, Corrao G, Del Vecchio BC, Di Leo V, et al. Hepatobiliary alterations in patients with inflammatory bowel disease: a multicenter study. Caprilli & Gruppo Italiano Studio Colon-Retto. Scand J Gastroenterol. 1998;33(1):93–8.

    CAS  PubMed  Google Scholar 

  11. Card TR, Solaymani-Dodaran M, West J. Incidence and mortality of primary sclerosing cholangitis in the UK: a population-based cohort study. J Hepatol. 2008;48(6):939–44.

    PubMed  Google Scholar 

  12. Deneau M, Jensen MK, Holmen J, Williams MS, Book LS, Guthery SL. Primary sclerosing cholangitis, autoimmune hepatitis, and overlap in Utah children: epidemiology and natural history. Hepatology (Baltimore, MD). 2013;58(4):1392–400.

    PubMed  Google Scholar 

  13. Kaplan GG, Laupland KB, Butzner D, Urbanski SJ, Lee SS. The burden of large and small duct primary sclerosing cholangitis in adults and children: a population-based analysis. Am J Gastroenterol. 2007;102(5):1042–9.

    PubMed  Google Scholar 

  14. Feldstein AE, Perrault J, El-Youssif M, Lindor KD, Freese DK, Angulo P. Primary sclerosing cholangitis in children: a long-term follow-up study. Hepatology (Baltimore, MD). 2003;38(1):210–7.

    PubMed  Google Scholar 

  15. Miloh T, Arnon R, Shneider B, Suchy F, Kerkar N. A retrospective single-center review of primary sclerosing cholangitis in children. Clin Gastroenterol Hepatol. 2009;7(2):239–45.

    PubMed  Google Scholar 

  16. Wilschanski M, Chait P, Wade JA, Davis L, Corey M, St Louis P, et al. Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis. Hepatology (Baltimore, MD). 1995;22(5):1415–22.

    CAS  PubMed  Google Scholar 

  17. Warren KW, Athanassiades S, Monge JI. Primary sclerosing cholangitis. A study of forty-two cases. Am J Surg. 1966;111(1):23–38.

    CAS  PubMed  Google Scholar 

  18. Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol. 2012;56(5):1181–8.

    PubMed  Google Scholar 

  19. Schrumpf E, Boberg KM. Epidemiology of primary sclerosing cholangitis. Best Pract Res Clin Gastroenterol. 2001;15(4):553–62.

    CAS  PubMed  Google Scholar 

  20. Batres LA, Russo P, Mathews M, Piccoli DA, Chuang E, Ruchelli E. Primary sclerosing cholangitis in children: a histologic follow-up study. Pediatr Dev Pathol. 2005;8(5):568–76.

    PubMed  Google Scholar 

  21. Dotson JL, Hyams JS, Markowitz J, LeLeiko NS, Mack DR, Evans JS, et al. Extraintestinal manifestations of pediatric inflammatory bowel disease and their relation to disease type and severity. J Pediatr Gastroenterol Nutr. 2010;51(2):140–5.

    PubMed  Google Scholar 

  22. Jose FA, Garnett EA, Vittinghoff E, Ferry GD, Winter HS, Baldassano RN, et al. Development of extraintestinal manifestations in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2009;15(1):63–8.

    PubMed  Google Scholar 

  23. Lunder AK, Hov JR, Borthne A, Gleditsch J, Johannesen G, Tveit K, et al. Prevalence of sclerosing cholangitis detected by magnetic resonance cholangiography in patients with long-term inflammatory bowel disease. Gastroenterology. 2016;151(4):660–9.e4.

    PubMed  Google Scholar 

  24. Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology (Baltimore, MD). 2010;51(2):660–78.

    CAS  PubMed  Google Scholar 

  25. Mells GF, Kaser A, Karlsen TH. Novel insights into autoimmune liver diseases provided by genome-wide association studies. J Autoimmun. 2013;46:41–54.

    CAS  PubMed  Google Scholar 

  26. Williamson KD, Chapman RW. Primary sclerosing cholangitis: a clinical update. Br Med Bull. 2015;114(1):53–64.

    CAS  PubMed  Google Scholar 

  27. Eksteen B, Grant AJ, Miles A, Curbishley SM, Lalor PF, Hubscher SG, et al. Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis. J Exp Med. 2004;200(11):1511–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Tabibian JH, O'Hara SP, Lindor KD. Primary sclerosing cholangitis and the microbiota: current knowledge and perspectives on etiopathogenesis and emerging therapies. Scand J Gastroenterol. 2014;49(8):901–8.

    PubMed  PubMed Central  Google Scholar 

  29. Quraishi MN, Sergeant M, Kay G, Iqbal T, Chan J, Constantinidou C, et al. The gut-adherent microbiota of PSC-IBD is distinct to that of IBD. Gut. 2017;66(2):386–8.

    PubMed  Google Scholar 

  30. Quraishi MN, Acharjee A, Beggs AD, Horniblow R, Tselepis C, Gkoutos G, et al. A pilot integrative analysis of colonic gene expression, gut microbiota, and immune infiltration in primary sclerosing cholangitis-inflammatory bowel disease: association of disease with bile acid pathways. J Crohns Colitis. 2020;14(7):935–47.

    PubMed  PubMed Central  Google Scholar 

  31. Torres J, Bao X, Goel A, Colombel JF, Pekow J, Jabri B, et al. The features of mucosa-associated microbiota in primary sclerosing cholangitis. Aliment Pharmacol Ther. 2016;43(7):790–801.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Kevans D, Tyler AD, Holm K, Jørgensen KK, Vatn MH, Karlsen TH, et al. Characterization of intestinal microbiota in ulcerative colitis patients with and without primary sclerosing cholangitis. J Crohns Colitis. 2016;10(3):330–7.

    CAS  PubMed  Google Scholar 

  33. Rossen NG, Fuentes S, Boonstra K, D'Haens GR, Heilig HG, Zoetendal EG, et al. The mucosa-associated microbiota of PSC patients is characterized by low diversity and low abundance of uncultured Clostridiales II. J Crohns Colitis. 2015;9(4):342–8.

    PubMed  Google Scholar 

  34. Lemoinne S, Kemgang A, Ben Belkacem K, Straube M, Jegou S, Corpechot C, et al. Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis. Gut. 2020;69(1):92–102.

    CAS  PubMed  Google Scholar 

  35. Rühlemann M, Liwinski T, Heinsen FA, Bang C, Zenouzi R, Kummen M, et al. Consistent alterations in faecal microbiomes of patients with primary sclerosing cholangitis independent of associated colitis. Aliment Pharmacol Ther. 2019;50(5):580–9.

    PubMed  PubMed Central  Google Scholar 

  36. Nakamoto N, Sasaki N, Aoki R, Miyamoto K, Suda W, Teratani T, et al. Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis. Nat Microbiol. 2019;4(3):492–503.

    CAS  PubMed  Google Scholar 

  37. Little R, Wine E, Kamath BM, Griffiths AM, Ricciuto A. Gut microbiome in primary sclerosing cholangitis: a review. World J Gastroenterol. 2020;26(21):2768–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Torres J, Palmela C, Brito H, Bao X, Ruiqi H, Moura-Santos P, et al. The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease. United European Gastroenterol J. 2018;6(1):112–22.

    CAS  PubMed  Google Scholar 

  39. Vaughn BP, Kaiser T, Staley C, Hamilton MJ, Reich J, Graiziger C, et al. A pilot study of fecal bile acid and microbiota profiles in inflammatory bowel disease and primary sclerosing cholangitis. Clin Exp Gastroenterol. 2019;12:9–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Loftus EV Jr, Harewood GC, Loftus CG, Tremaine WJ, Harmsen WS, Zinsmeister AR, et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut. 2005;54(1):91–6.

    PubMed  PubMed Central  Google Scholar 

  41. de Vries AB, Janse M, Blokzijl H, Weersma RK. Distinctive inflammatory bowel disease phenotype in primary sclerosing cholangitis. World J Gastroenterol. 2015;21(6):1956–71.

    PubMed  PubMed Central  Google Scholar 

  42. Halliday JS, Djordjevic J, Lust M, Culver EL, Braden B, Travis SP, et al. A unique clinical phenotype of primary sclerosing cholangitis associated with Crohn’s disease. J Crohns Colitis. 2012;6(2):174–81.

    CAS  PubMed  Google Scholar 

  43. 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(4):451–6.

    CAS  PubMed  Google Scholar 

  44. Schaeffer DF, Win LL, Hafezi-Bakhtiari S, Cino M, Hirschfield GM, El-Zimaity H. The phenotypic expression of inflammatory bowel disease in patients with primary sclerosing cholangitis differs in the distribution of colitis. Dig Dis Sci. 2013;58(9):2608–14.

    CAS  PubMed  Google Scholar 

  45. Ricciuto A, Hansen BE, Ngo B, Aloi M, Walters TD, Church PC, et al. Primary sclerosing cholangitis in children with inflammatory bowel diseases is associated with milder clinical activity but more frequent subclinical inflammation and growth impairment. Clin Gastroenterol Hepatol. 2020;18(7):1509–17.e7.

    PubMed  Google Scholar 

  46. Ricciuto A, Fish J, Carman N, Walters TD, Church PC, Hansen BE, et al. Symptoms do not correlate with findings from colonoscopy in children with inflammatory bowel disease and primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 2018;16(7):1098–105.e1.

    PubMed  Google Scholar 

  47. Marelli L, Xirouchakis E, Kalambokis G, Cholongitas E, Hamilton MI, Burroughs AK. Does the severity of primary sclerosing cholangitis influence the clinical course of associated ulcerative colitis? Gut. 2011;60(9):1224–8.

    PubMed  Google Scholar 

  48. Mouchli MA, Singh S, Boardman L, Bruining DH, Lightner AL, Rosen CB, et al. Natural history of established and de novo inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Inflamm Bowel Dis. 2018;24(5):1074–81.

    PubMed  PubMed Central  Google Scholar 

  49. Cangemi JR, Wiesner RH, Beaver SJ, Ludwig J, MacCarty RL, Dozois RR, et al. Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis. Gastroenterology. 1989;96(3):790–4.

    CAS  PubMed  Google Scholar 

  50. Cholongitas E, Shusang V, Papatheodoridis GV, Marelli L, Manousou P, Rolando N, et al. Risk factors for recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transplant. 2008;14(2):138–43.

    Google Scholar 

  51. Peverelle M, Paleri S, Hughes J, De Cruz P, Gow PJ. Activity of inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis predicts poorer clinical outcomes. Inflamm Bowel Dis. 2020;26(12):1901–8.

    PubMed  Google Scholar 

  52. Ricciuto A, Kamath BM, Griffiths AM. The IBD and PSC phenotypes of PSC-IBD. Curr Gastroenterol Rep. 2018;20(4):16.

    PubMed  Google Scholar 

  53. Bjornsson E, Chari S, Silveira M, Gossard A, Takahashi N, Smyrk T, et al. Primary sclerosing cholangitis associated with elevated immunoglobulin G4: clinical characteristics and response to therapy. Am J Ther. 2011;18(3):198–205.

    PubMed  Google Scholar 

  54. Lindor KD, Kowdley KV, Harrison ME. ACG clinical guideline: primary sclerosing cholangitis. Am J Gastroenterol. 2015;110(5):646–59. quiz 60

    CAS  Google Scholar 

  55. Patil K, Ricciuto A, Alsharief A, Al-Rayahi J, Amirabadi A, Church PC, et al. Magnetic resonance cholangiopancreatography severity predicts disease outcomes in pediatric primary sclerosing cholangitis: a reliability and validity study. Hepatol Commun. 2020;4(2):208–18.

    CAS  PubMed  Google Scholar 

  56. MacCarty RL, LaRusso NF, Wiesner RH, Ludwig J. Primary sclerosing cholangitis: findings on cholangiography and pancreatography. Radiology. 1983;149(1):39–44.

    CAS  Google Scholar 

  57. Deneau MR, El-Matary W, Valentino PL, Abdou R, Alqoaer K, Amin M, et al. The natural history of primary sclerosing cholangitis in 781 children: a multicenter, international collaboration. Hepatology (Baltimore, MD). 2017;66(2):518–27.

    CAS  PubMed  Google Scholar 

  58. Lazaridis KN, LaRusso NF. Primary sclerosing cholangitis. N Engl J Med. 2016;375(12):1161–70.

    PubMed  PubMed Central  Google Scholar 

  59. Fosby B, Karlsen TH, Melum E. Recurrence and rejection in liver transplantation for primary sclerosing cholangitis. World J Gastroenterol. 2012;18(1):1–15.

    PubMed  PubMed Central  Google Scholar 

  60. Deneau MR, Mack C, Abdou R, Amin M, Amir A, Auth M, et al. Gamma glutamyltransferase reduction is associated with favorable outcomes in pediatric primary sclerosing cholangitis. Hepatol Commun. 2018;2(11):1369–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Soetikno RM, Lin OS, Heidenreich PA, Young HS, Blackstone MO. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc. 2002;56(1):48–54.

    PubMed  Google Scholar 

  62. El-Matary W, Guthery SL, Amir AZ, DiGuglielmo M, Draijer LG, Furuya KN, et al. Colorectal dysplasia and cancer in pediatric-onset ulcerative colitis associated with primary sclerosing cholangitis. Clin Gastroenterol Hepatol. 2020;19(5):1067–1070.e2.

    PubMed  PubMed Central  Google Scholar 

  63. Ponsioen CY, Vrouenraets SM, Prawirodirdjo W, Rajaram R, Rauws EA, Mulder CJ, et al. Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population. Gut. 2002;51(4):562–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol. 2004;99(3):523–6.

    PubMed  Google Scholar 

  65. Claessen MM, Vleggaar FP, Tytgat KM, Siersema PD, van Buuren HR. High lifetime risk of cancer in primary sclerosing cholangitis. J Hepatol. 2009;50(1):158–64.

    PubMed  Google Scholar 

  66. Deneau M, Adler DG, Schwartz JJ, Hutson W, Sorensen J, Book L, et al. Cholangiocarcinoma in a 17-year-old boy with primary sclerosing cholangitis and inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2011;52(5):617–20.

    PubMed  Google Scholar 

  67. Bjornsson E, Olsson R, Bergquist A, Lindgren S, Braden B, Chapman RW, et al. The natural history of small-duct primary sclerosing cholangitis. Gastroenterology. 2008;134(4):975–80.

    PubMed  Google Scholar 

  68. Deneau MR, Mack C, Perito ER, Ricciuto A, Valentino PL, Amin M, et al. The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) index: a prognostic tool for children. Hepatology (Baltimore, MD). 2020;73(3):1074–87.

    PubMed  PubMed Central  Google Scholar 

  69. Tabibian JH, Lindor KD. Primary sclerosing cholangitis: a review and update on therapeutic developments. Expert Rev Gastroenterol Hepatol. 2013;7(2):103–14.

    CAS  PubMed  Google Scholar 

  70. Gilger MA, Gann ME, Opekun AR, Gleason WA Jr. Efficacy of ursodeoxycholic acid in the treatment of primary sclerosing cholangitis in children. J Pediatr Gastroenterol Nutr. 2000;31(2):136–41.

    CAS  PubMed  Google Scholar 

  71. Deneau MR, Mack C, Mogul D, Perito ER, Valentino PL, Amir AZ, et al. Oral vancomycin, ursodeoxycholic acid or no therapy for pediatric primary sclerosing cholangitis: a matched analysis. Hepatology (Baltimore, MD). 2020;73(3):1061–73.

    Google Scholar 

  72. Triantos CK, Koukias NM, Nikolopoulou VN, Burroughs AK. Meta-analysis: ursodeoxycholic acid for primary sclerosing cholangitis. Aliment Pharmacol Ther. 2011;34(8):901–10.

    CAS  PubMed  Google Scholar 

  73. Suri J, Patwardhan V, Bonder A. Pharmacologic management of primary sclerosing cholangitis: what’s in the pipeline? Expert Rev Gastroenterol Hepatol. 2019;13(8):723–9.

    CAS  PubMed  Google Scholar 

  74. Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology (Baltimore, MD). 2009;50(3):808–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Sabino J, Vieira-Silva S, Machiels K, Joossens M, Falony G, Ballet V, et al. Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD. Gut. 2016;65(10):1681–9.

    CAS  PubMed  Google Scholar 

  76. Chapman MH, Thorburn D, Hirschfield GM, Webster GGJ, Rushbrook SM, Alexander G, et al. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut. 2019;68(8):1356–78.

    CAS  PubMed  Google Scholar 

  77. Cox KL, Cox KM. Oral vancomycin: treatment of primary sclerosing cholangitis in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1998;27(5):580–3.

    CAS  PubMed  Google Scholar 

  78. Davies YK, Cox KM, Abdullah BA, Safta A, Terry AB, Cox KL. Long-term treatment of primary sclerosing cholangitis in children with oral vancomycin: an immunomodulating antibiotic. J Pediatr Gastroenterol Nutr. 2008;47(1):61–7.

    CAS  PubMed  Google Scholar 

  79. Tabibian JH, Weeding E, Jorgensen RA, Petz JL, Keach JC, Talwalkar JA, et al. Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis – a pilot study. Aliment Pharmacol Ther. 2013;37(6):604–12.

    CAS  PubMed  Google Scholar 

  80. Damman JL, Rodriguez EA, Ali AH, Buness CW, Cox KL, Carey EJ, et al. Review article: the evidence that vancomycin is a therapeutic option for primary sclerosing cholangitis. Aliment Pharmacol Ther. 2018;47(7):886–95.

    CAS  PubMed  Google Scholar 

  81. Abarbanel DN, Seki SM, Davies Y, Marlen N, Benavides JA, Cox K, et al. Immunomodulatory effect of vancomycin on Treg in pediatric inflammatory bowel disease and primary sclerosing cholangitis. J Clin Immunol. 2013;33(2):397–406.

    CAS  PubMed  Google Scholar 

  82. Ali AH, Damman J, Shah SB, Davies Y, Hurwitz M, Stephen M, et al. Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. Scand J Gastroenterol. 2020;55(8):941–50.

    CAS  PubMed  Google Scholar 

  83. Laborda TJ, Jensen MK, Kavan M, Deneau M. Treatment of primary sclerosing cholangitis in children. World J Hepatol. 2019;11(1):19–36.

    PubMed  PubMed Central  Google Scholar 

  84. Tan LZ, Reilly CR, Steward-Harrison LC, Balouch F, Muir R, Lewindon PJ. Oral vancomycin induces clinical and mucosal remission of colitis in children with primary sclerosing cholangitis-ulcerative colitis. Gut. 2019;68(8):1533–5.

    CAS  PubMed  Google Scholar 

  85. Färkkilä M, Karvonen AL, Nurmi H, Nuutinen H, Taavitsainen M, Pikkarainen P, et al. Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo-controlled trial. Hepatology (Baltimore, MD). 2004;40(6):1379–86.

    PubMed  Google Scholar 

  86. Silveira MG, Torok NJ, Gossard AA, Keach JC, Jorgensen RA, Petz JL, et al. Minocycline in the treatment of patients with primary sclerosing cholangitis: results of a pilot study. Am J Gastroenterol. 2009;104(1):83–8.

    CAS  PubMed  Google Scholar 

  87. Tabibian JH, Gossard A, El-Youssef M, Eaton JE, Petz J, Jorgensen R, et al. Prospective clinical trial of rifaximin therapy for patients with primary sclerosing cholangitis. Am J Ther. 2017;24(1):e56–63.

    PubMed  PubMed Central  Google Scholar 

  88. Allegretti JR, Kassam Z, Carrellas M, Mullish BH, Marchesi JR, Pechlivanis A, et al. Fecal microbiota transplantation in patients with primary sclerosing cholangitis: a pilot clinical trial. Am J Gastroenterol. 2019;114(7):1071–9.

    PubMed  Google Scholar 

  89. Kowdley KV, Vuppalanchi R, Levy C, Floreani A, Andreone P, LaRusso NF, et al. A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis. J Hepatol. 2020;73(1):94–101.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Trauner M, Gulamhusein A, Hameed B, Caldwell S, Shiffman ML, Landis C, et al. The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with primary sclerosing cholangitis. Hepatology (Baltimore, MD). 2019;70(3):788–801.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Hegade VS, Jones DE, Hirschfield GM. Apical sodium-dependent transporter inhibitors in primary biliary cholangitis and primary sclerosing cholangitis. Digestive diseases (Basel, Switzerland). 2017;35(3):267–74.

    PubMed  Google Scholar 

  92. Johnson GK, Saeian K, Geenen JE. Primary sclerosing cholangitis treated by endoscopic biliary dilation: review and long-term follow-up evaluation. Curr Gastroenterol Rep. 2006;8(2):147–55.

    PubMed  Google Scholar 

  93. Grant AJ, Lalor PF, Hübscher SG, Briskin M, Adams DH. MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease). Hepatology (Baltimore, MD). 2001;33(5):1065–72.

    CAS  PubMed  Google Scholar 

  94. Borchers AT, Shimoda S, Bowlus C, Keen CL, Gershwin ME. Lymphocyte recruitment and homing to the liver in primary biliary cirrhosis and primary sclerosing cholangitis. Semin Immunopathol. 2009;31(3):309–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Christensen B, Micic D, Gibson PR, Yarur A, Bellaguarda E, Corsello P, et al. Vedolizumab in patients with concurrent primary sclerosing cholangitis and inflammatory bowel disease does not improve liver biochemistry but is safe and effective for the bowel disease. Aliment Pharmacol Ther. 2018;47(6):753–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Caron B, Peyrin-Biroulet L, Pariente B, Bouhnik Y, Seksik P, Bouguen G, et al. Vedolizumab therapy is ineffective for primary sclerosing cholangitis in patients with inflammatory bowel disease: a GETAID Multicentre Cohort Study. J Crohns Colitis. 2019;13(10):1239–47.

    PubMed  Google Scholar 

  97. Lynch KD, Chapman RW, Keshav S, Montano-Loza AJ, Mason AL, Kremer AE, et al. Effects of vedolizumab in patients with primary sclerosing cholangitis and inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2020;18(1):179–87.e6.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Laborda TJ, Ricciuto A, Aumar M, Carman N, DiGuglielmo M, Draijer LG, et al. Vedolizumab therapy in children with primary sclerosing cholangitis: data from the pediatric primary sclerosing cholangitis consortium. J Pediatr Gastroenterol Nutr. 2020;71(4):459–64.

    CAS  PubMed  Google Scholar 

  99. Venkat VL, Ranganathan S, Sindhi R. The challenges of liver transplantation in children with primary sclerosing cholangitis. Expert Rev Gastroenterol Hepatol. 2015;9(3):289–94.

    CAS  PubMed  Google Scholar 

  100. Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, et al. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2014;59(1):112–31.

    PubMed  Google Scholar 

  101. Miloh T, Anand R, Yin W, Vos M, Kerkar N, Alonso E, et al. Pediatric liver transplantation for primary sclerosing cholangitis. Liver Transplant. 2011;17(8):925–33.

    Google Scholar 

  102. Venkat VL, Ranganathan S, Mazariegos GV, Sun Q, Sindhi R. Recurrence of primary sclerosing cholangitis in pediatric liver transplant recipients. Liver Transplant. 2014;20(6):679–86.

    Google Scholar 

  103. Jimenez-Rivera C, Ling SC, Ahmed N, Yap J, Aglipay M, Barrowman N, et al. Incidence and characteristics of autoimmune hepatitis. Pediatrics. 2015;136(5):e1237–48.

    PubMed  Google Scholar 

  104. Gregorio GV, Portmann B, Karani J, Harrison P, Donaldson PT, Vergani D, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology (Baltimore, MD). 2001;33(3):544–53.

    CAS  PubMed  Google Scholar 

  105. Mieli-Vergani G, Vergani D. Paediatric autoimmune liver disease. Arch Dis Child. 2013;98(12):1012–7.

    PubMed  Google Scholar 

  106. Mieli-Vergani G, Vergani D. Autoimmune hepatitis in children: what is different from adult AIH? Semin Liver Dis. 2009;29(3):297–306.

    PubMed  Google Scholar 

  107. Gregorio GV, Portmann B, Reid F, Donaldson PT, Doherty DG, McCartney M, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology (Baltimore, MD). 1997;25(3):541–7.

    CAS  PubMed  Google Scholar 

  108. Manns MP, Lohse AW, Vergani D. Autoimmune hepatitis–update 2015. J Hepatol. 2015;62(1 Suppl):S100–11.

    PubMed  Google Scholar 

  109. Singh H, Balouch F, Noble C, Lewindon P. Evolving practice and changing phenotype in pediatric autoimmune liver disease: outcomes from an australian center. J Pediatr Gastroenterol Nutr. 2018;67(1):80–5.

    PubMed  Google Scholar 

  110. Mieli-Vergani G, Vergani D. Autoimmune hepatitis. Nat Rev Gastroenterol Hepatol. 2011;8(6):320–9.

    CAS  PubMed  Google Scholar 

  111. Radhakrishnan KR, Alkhouri N, Worley S, Arrigain S, Hupertz V, Kay M, et al. Autoimmune hepatitis in children–impact of cirrhosis at presentation on natural history and long-term outcome. Dig Liver Dis. 2010;42(10):724–8.

    PubMed  Google Scholar 

  112. Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the Study of Liver Diseases. Hepatology (Baltimore, Md). 2020;72(2):671–722.

    PubMed  Google Scholar 

  113. Floreani A, Liberal R, Vergani D, Mieli-Vergani G. Autoimmune hepatitis: contrasts and comparisons in children and adults – a comprehensive review. J Autoimmun. 2013;46:7–16.

    PubMed  Google Scholar 

  114. Manns MP, Woynarowski M, Kreisel W, Lurie Y, Rust C, Zuckerman E, et al. Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. Gastroenterology. 2010;139(4):1198–206.

    CAS  PubMed  Google Scholar 

  115. Liberal R, Vergani D, Mieli-Vergani G. Recurrence of autoimmune liver disease and inflammatory bowel disease after pediatric liver transplantation. Liver Transplant. 2016;22(9):1275–83.

    Google Scholar 

  116. Liberal R, Longhi MS, Grant CR, Mieli-Vergani G, Vergani D. Autoimmune hepatitis after liver transplantation. Clin Gastroenterol Hepatol. 2012;10(4):346–53.

    PubMed  Google Scholar 

  117. Liberal R, Zen Y, Mieli-Vergani G, Vergani D. Liver transplantation and autoimmune liver diseases. Liver Transplant. 2013;19(10):1065–77.

    Google Scholar 

  118. Dvorchik I, Subotin M, Demetris AJ, Fung JJ, Starzl TE, Wieand S, et al. Effect of liver transplantation on inflammatory bowel disease in patients with primary sclerosing cholangitis. Hepatology (Baltimore, MD). 2002;35(2):380–4.

    PubMed  PubMed Central  Google Scholar 

  119. Verdonk RC, Dijkstra G, Haagsma EB, Shostrom VK, Van den Berg AP, Kleibeuker JH, et al. Inflammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2006;6(6):1422–9.

    CAS  Google Scholar 

  120. Singh S, Loftus EV Jr, Talwalkar JA. Inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Am J Gastroenterol. 2013;108(9):1417–25.

    CAS  PubMed  Google Scholar 

  121. Boberg KM, Chapman RW, Hirschfield GM, Lohse AW, Manns MP, Schrumpf E. Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue. J Hepatol. 2011;54(2):374–85.

    PubMed  Google Scholar 

  122. Mieli-Vergani G, Vergani D, Baumann U, Czubkowski P, Debray D, Dezsofi A, et al. Diagnosis and management of pediatric autoimmune liver disease: ESPGHAN hepatology committee position statement. J Pediatr Gastroenterol Nutr. 2018;66(2):345–60.

    PubMed  Google Scholar 

  123. Rojas CP, Bodicharla R, Campuzano-Zuluaga G, Hernandez L, Rodriguez MM. Autoimmune hepatitis and primary sclerosing cholangitis in children and adolescents. Fetal Pediatr Pathol. 2014;33(4):202–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, et al. Diagnosis and management of autoimmune hepatitis. Hepatology (Baltimore, MD). 2010;51(6):2193–213.

    CAS  PubMed  Google Scholar 

  125. Rodrigues AT, Liu PM, Fagundes ED, Queiroz TC, de Souza Haueisen Barbosa P, Silva SL, et al. Clinical characteristics and prognosis in children and adolescents with autoimmune hepatitis and overlap syndrome. J Pediatr Gastroenterol Nutr. 2016;63(1):76–81.

    CAS  PubMed  Google Scholar 

  126. European Association for the Study of the L. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237–67.

    Google Scholar 

  127. Beuers U, Hubers LM, Doorenspleet M, de Buy M, Wenniger L, Klarenbeek PL, Boonstra K, et al. IgG4-associated cholangitis--a mimic of PSC. Digestive diseases (Basel, Switzerland). 2015;33(Suppl 2):176–80.

    PubMed  Google Scholar 

  128. Dastis SN, Latinne D, Sempoux C, Geubel AP. Ulcerative colitis associated with IgG4 cholangitis: similar features in two HLA identical siblings. J Hepatol. 2009;51(3):601–5.

    CAS  PubMed  Google Scholar 

  129. Hirano K, Kawabe T, Yamamoto N, Nakai Y, Sasahira N, Tsujino T, et al. Serum IgG4 concentrations in pancreatic and biliary diseases. Clin Chim Acta. 2006;367(1–2):181–4.

    CAS  PubMed  Google Scholar 

  130. Mendes FD, Jorgensen R, Keach J, Katzmann JA, Smyrk T, Donlinger J, et al. Elevated serum IgG4 concentration in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2006;101(9):2070–5.

    CAS  PubMed  Google Scholar 

  131. Zhang L, Lewis JT, Abraham SC, Smyrk TC, Leung S, Chari ST, et al. IgG4+ plasma cell infiltrates in liver explants with primary sclerosing cholangitis. Am J Surg Pathol. 2010;34(1):88–94.

    PubMed  Google Scholar 

  132. Ghazale A, Chari ST, Zhang L, Smyrk TC, Takahashi N, Levy MJ, et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134(3):706–15.

    PubMed  Google Scholar 

  133. Ohara H, Okazaki K, Tsubouchi H, Inui K, Kawa S, Kamisawa T, et al. Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 2012. J Hepatobiliary Pancreat Sci. 2012;19(5):536–42.

    PubMed  Google Scholar 

  134. Conway R, Low C, Coughlan RJ, O'Donnell MJ, Carey JJ. Risk of liver injury among methotrexate users: a meta-analysis of randomised controlled trials. Semin Arthritis Rheum. 2015;45(2):156–62.

    CAS  PubMed  Google Scholar 

  135. Fournier MR, Klein J, Minuk GY, Bernstein CN. Changes in liver biochemistry during methotrexate use for inflammatory bowel disease. Am J Gastroenterol. 2010;105(7):1620–6.

    CAS  PubMed  Google Scholar 

  136. Te HS, Schiano TD, Kuan SF, Hanauer SB, Conjeevaram HS, Baker AL. Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease. Am J Gastroenterol. 2000;95(11):3150–6.

    CAS  PubMed  Google Scholar 

  137. Scherkenbach LA, Stumpf JL. Methotrexate for the management of Crohn’s disease in children. Ann Pharmacother. 2015;50(1):60–9.

    PubMed  Google Scholar 

  138. Sunseri W, Hyams JS, Lerer T, Mack DR, Griffiths AM, Otley AR, et al. Retrospective cohort study of methotrexate use in the treatment of pediatric Crohn’s disease. Inflamm Bowel Dis. 2014;20(8):1341–5.

    PubMed  Google Scholar 

  139. Turner D, Doveh E, Cohen A, Wilson ML, Grossman AB, Rosh JR, et al. Efficacy of oral methotrexate in paediatric Crohn’s disease: a multicentre propensity score study. Gut. 2014;64(12):1898–904.

    PubMed  Google Scholar 

  140. Valentino PL, Church PC, Shah PS, Beyene J, Griffiths AM, Feldman BM, et al. Hepatotoxicity caused by methotrexate therapy in children with inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 2014;20(1):47–59.

    PubMed  Google Scholar 

  141. Haisma SM, Lijftogt T, Kindermann A, Damen G, de Ridder L, Escher JC, et al. Methotrexate for maintaining remission in paediatric Crohn’s patients with prior failure or intolerance to thiopurines: a multicenter cohort study. J Crohns Colitis. 2015;9(4):305–11.

    PubMed  Google Scholar 

  142. 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.

    PubMed  Google Scholar 

  143. Kalb RE, Strober B, Weinstein G, Lebwohl M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol. 2009;60(5):824–37.

    PubMed  Google Scholar 

  144. Bousvaros A. Use of immunomodulators and biologic therapies in children with inflammatory bowel disease. Expert Rev Clin Immunol. 2010;6(4):659–66.

    CAS  PubMed  Google Scholar 

  145. Gisbert JP, González-Lama Y, Maté J. Thiopurine-induced liver injury in patients with inflammatory bowel disease: a systematic review. Am J Gastroenterol. 2007;102(7):1518–27.

    CAS  PubMed  Google Scholar 

  146. Lee MN, Kang B, Choi SY, Kim MJ, Woo SY, Kim JW, et al. Relationship between azathioprine dosage, 6-thioguanine nucleotide levels, and therapeutic response in pediatric patients with IBD treated with azathioprine. Inflamm Bowel Dis. 2015;21(5):1054–62.

    CAS  PubMed  Google Scholar 

  147. Riello L, Talbotec C, Garnier-Lengliné H, Pigneur B, Svahn J, Canioni D, et al. Tolerance and efficacy of azathioprine in pediatric Crohn’s disease. Inflamm Bowel Dis. 2011;17(10):2138–43.

    PubMed  Google Scholar 

  148. Björnsson ES, Gu J, Kleiner DE, Chalasani N, Hayashi PH, Hoofnagle JH. Azathioprine and 6-mercaptopurine-induced liver injury: clinical features and outcomes. J Clin Gastroenterol. 2017;51(1):63–9.

    PubMed  PubMed Central  Google Scholar 

  149. Haboubi NY, Ali HH, Whitwell HL, Ackrill P. Role of endothelial cell injury in the spectrum of azathioprine-induced liver disease after renal transplant: light microscopy and ultrastructural observations. Am J Gastroenterol. 1988;83(3):256–61.

    CAS  PubMed  Google Scholar 

  150. Dubinsky MC, Vasiliauskas EA, Singh H, Abreu MT, Papadakis KA, Tran T, et al. 6-thioguanine can cause serious liver injury in inflammatory bowel disease patients. Gastroenterology. 2003;125(2):298–303.

    CAS  PubMed  Google Scholar 

  151. Calabrese E, Hanauer SB. Assessment of non-cirrhotic portal hypertension associated with thiopurine therapy in inflammatory bowel disease. J Crohns Colitis. 2011;5(1):48–53.

    PubMed  Google Scholar 

  152. Seiderer J, Zech CJ, Reinisch W, Lukas M, Diebold J, Wrba F, et al. A multicenter assessment of liver toxicity by MRI and biopsy in IBD patients on 6-thioguanine. J Hepatol. 2005;43(2):303–9.

    CAS  PubMed  Google Scholar 

  153. Musumba CO. Review article: the association between nodular regenerative hyperplasia, inflammatory bowel disease and thiopurine therapy. Aliment Pharmacol Ther. 2013;38(9):1025–37.

    CAS  PubMed  Google Scholar 

  154. Khokhar OS, Lewis JH. Hepatotoxicity of agents used in the management of inflammatory bowel disease. Dig Dis (Basel, Switzerland). 2010;28(3):508–18.

    Google Scholar 

  155. Dubinsky MC, Lamothe S, Yang HY, Targan SR, Sinnett D, Théorêt Y, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology. 2000;118(4):705–13.

    CAS  PubMed  Google Scholar 

  156. Konidari A, Anagnostopoulos A, Bonnett LJ, Pirmohamed M, El-Matary W. Thiopurine monitoring in children with inflammatory bowel disease: a systematic review. Br J Clin Pharmacol. 2014;78(3):467–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Connor V. Anti-TNF therapies: a comprehensive analysis of adverse effects associated with immunosuppression. Rheumatol Int. 2011;31(3):327–37.

    CAS  PubMed  Google Scholar 

  158. Vaz JL, Fernandes V, Nogueira F, Arnóbio A, Levy RA. Infliximab-induced autoantibodies: a multicenter study. Clin Rheumatol. 2016;35(2):325–32.

    PubMed  Google Scholar 

  159. Weiler-Normann C, Schramm C, Quaas A, Wiegard C, Glaubke C, Pannicke N, et al. Infliximab as a rescue treatment in difficult-to-treat autoimmune hepatitis. J Hepatol. 2013;58(3):529–34.

    CAS  PubMed  Google Scholar 

  160. Ghabril M, Bonkovsky HL, Kum C, Davern T, Hayashi PH, Kleiner DE, et al. Liver injury from tumor necrosis factor-α antagonists: analysis of thirty-four cases. Clin Gastroenterol Hepatol. 2013;11(5):558–64.e3.

    CAS  PubMed  Google Scholar 

  161. 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;41(10):972–9.

    CAS  PubMed  Google Scholar 

  162. Björnsson ES, Gunnarsson BI, Gröndal G, Jonasson JG, Einarsdottir R, Ludviksson BR, et al. Risk of drug-induced liver injury from tumor necrosis factor antagonists. Clin Gastroenterol Hepatol. 2015;13(3):602–8.

    PubMed  Google Scholar 

  163. Church PC, Guan J, Walters TD, Frost K, Assa A, Muise AM, et al. Infliximab maintains durable response and facilitates catch-up growth in luminal pediatric Crohn’s disease. Inflamm Bowel Dis. 2014;20(7):1177–86.

    PubMed  Google Scholar 

  164. Ricciuto A, Kamath BM, Walters TD, Frost K, Carman N, Church PC, et al. New onset autoimmune hepatitis during anti-tumor necrosis factor-alpha treatment in children. J Pediatr. 2018;194:128–35.e1.

    CAS  PubMed  Google Scholar 

  165. Loras C, Gisbert JP, Mínguez 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.

    CAS  PubMed  Google Scholar 

  166. Lin MV, Blonski W, Buchner AM, Reddy KR, Lichtenstein GR. The influence of anti-TNF therapy on the course of chronic hepatitis C virus infection in patients with inflammatory bowel disease. Dig Dis Sci. 2013;58(4):1149–56.

    CAS  PubMed  Google Scholar 

  167. Park SH, Yang SK, Park SK, Kim JW, Yang DH, Jung KW, et al. Efficacy of hepatitis A vaccination and factors impacting on seroconversion in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2014;20(1):69–74.

    PubMed  Google Scholar 

  168. Boyer DL, Li BU, Fyda JN, Friedman RA. Sulfasalazine-induced hepatotoxicity in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1989;8(4):528–32.

    CAS  PubMed  Google Scholar 

  169. Bashir RM, Lewis JH. Hepatotoxicity of drugs used in the treatment of gastrointestinal disorders. Gastroenterol Clin N Am. 1995;24(4):937–67.

    CAS  Google Scholar 

  170. Jobanputra P, Amarasena R, Maggs F, Homer D, Bowman S, Rankin E, et al. Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: a case series from a local surveillance of serious adverse events. BMC Musculoskelet Disord. 2008;9:48.

    PubMed  PubMed Central  Google Scholar 

  171. Ribe J, Benkov KJ, Thung SN, Shen SC, LeLeiko NS. Fatal massive hepatic necrosis: a probable hypersensitivity reaction to sulfasalazine. Am J Gastroenterol. 1986;81(3):205–8.

    CAS  PubMed  Google Scholar 

  172. Namias A, Bhalotra R, Donowitz M. Reversible sulfasalazine-induced granulomatous hepatitis. J Clin Gastroenterol. 1981;3(2):193–8.

    CAS  PubMed  Google Scholar 

  173. Quallich LG, Greenson J, Haftel HM, Fontana RJ. Is it Crohn’s disease? A severe systemic granulomatous reaction to sulfasalazine in patient with rheumatoid arthritis. BMC Gastroenterol. 2001;1:8.

    CAS  PubMed  PubMed Central  Google Scholar 

  174. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Braun M, Fraser GM, Kunin M, Salamon F, Tur-Kaspa R. Mesalamine-induced granulomatous hepatitis. Am J Gastroenterol. 1999;94(7):1973–4.

    CAS  PubMed  Google Scholar 

  176. Stelzer T, Kohler S, Marques Maggio E, Heuss LT. An unusual cause of febrile hepatitis. BMJ Case Rep. 2015;2015

    Google Scholar 

  177. Stoschus B, Meybehm M, Spengler U, Scheurlen C, Sauerbruch T. Cholestasis associated with mesalazine therapy in a patient with Crohn’s disease. J Hepatol. 1997;26(2):425–8.

    CAS  PubMed  Google Scholar 

  178. Hautekeete ML, Bourgeois N, Potvin P, Duville L, Reynaert H, Devis G, et al. Hypersensitivity with hepatotoxicity to mesalazine after hypersensitivity to sulfasalazine. Gastroenterology. 1992;103(6):1925–7.

    CAS  PubMed  Google Scholar 

  179. Deltenre P, Berson A, Marcellin P, Degott C, Biour M, Pessayre D. Mesalazine (5-aminosalicylic acid) induced chronic hepatitis. Gut. 1999;44(6):886–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  180. 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.

    PubMed  Google Scholar 

  181. 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.

    PubMed  Google Scholar 

  182. Fousekis FS, Theopistos VI, Katsanos KH, Tsianos EV, Christodoulou DK. Hepatobiliary manifestations and complications in inflammatory bowel disease: a review. Gastroenterology Res. 2018;11(2):83–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Shah ED, Coburn ES, Nayyar A, Lee KJ, Koliani-Pace JL, Siegel CA. Systematic review: hepatosplenic T-cell lymphoma on biologic therapy for inflammatory bowel disease, including data from the Food and Drug Administration Adverse Event Reporting System. Aliment Pharmacol Ther. 2020;51(5):527–33.

    PubMed  PubMed Central  Google Scholar 

  184. Mason M, Siegel CA. Do inflammatory bowel disease therapies cause cancer? Inflamm Bowel Dis. 2013;19(6):1306–21.

    PubMed  Google Scholar 

  185. Biancone L, Onali S, Petruzziello C, Calabrese E, Pallone F. Cancer and immunomodulators in inflammatory bowel diseases. Inflamm Bowel Dis. 2015;21(3):674–98.

    PubMed  Google Scholar 

  186. Dahmus J, Rosario M, Clarke K. Risk of lymphoma associated with anti-TNF therapy in patients with inflammatory bowel disease: implications for therapy. Clin Exp Gastroenterol. 2020;13:339–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Deepak P, Sifuentes H, Sherid M, Stobaugh D, Sadozai Y, Ehrenpreis ED. T-cell non-Hodgkin’s lymphomas reported to the FDA AERS with tumor necrosis factor-alpha (TNF-α) inhibitors: results of the REFURBISH study. Am J Gastroenterol. 2013;108(1):99–105.

    CAS  PubMed  Google Scholar 

  188. Lemaitre M, Kirchgesner J, Rudnichi A, Carrat F, Zureik M, Carbonnel F, et al. Association between use of thiopurines or tumor necrosis factor antagonists alone or in combination and risk of lymphoma in patients with inflammatory bowel disease. JAMA. 2017;318(17):1679–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  189. 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.

    CAS  PubMed  Google Scholar 

  190. 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 (Baltimore, MD). 2007;45(5):1267–74.

    PubMed  Google Scholar 

  191. Ehlin AG, Montgomery SM, Ekbom A, Pounder RE, Wakefield AJ. Prevalence of gastrointestinal diseases in two British national birth cohorts. Gut. 2003;52(8):1117–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  192. Lin JN, Lin CL, Lin MC, Lai CH, Lin HH, Kao CH. Pyogenic liver abscess in patients with inflammatory bowel disease: a nationwide cohort study. Liver Int. 2016;36(1):136–44.

    PubMed  Google Scholar 

  193. Margalit M, Elinav H, Ilan Y, Shalit M. Liver abscess in inflammatory bowel disease: report of two cases and review of the literature. J Gastroenterol Hepatol. 2004;19(12):1338–42.

    PubMed  Google Scholar 

  194. Nylund CM, Goudie A, Garza JM, Crouch G, Denson LA. Venous thrombotic events in hospitalized children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2013;56(5):485–91.

    PubMed  Google Scholar 

  195. Maconi G, Bolzacchini E, Dell'Era A, Russo U, Ardizzone S, de Franchis R. Portal vein thrombosis in inflammatory bowel diseases: a single-center case series. J Crohns Colitis. 2012;6(3):362–7.

    PubMed  Google Scholar 

  196. Naymagon L, Tremblay D, Zubizarreta N, Moshier E, Naymagon S, Mascarenhas J, et al. The natural history, treatments, and outcomes of portal vein thrombosis in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2020;27(2):215–23.

    PubMed Central  Google Scholar 

  197. Kraut J, Berman JH, Gunasekaran TS, Allen R, McFadden J, Messersmith R, et al. Hepatic vein thrombosis (Budd-Chiari syndrome) in an adolescent with ulcerative colitis. J Pediatr Gastroenterol Nutr. 1997;25(4):417–20.

    CAS  PubMed  Google Scholar 

  198. Rahhal RM, Pashankar DS, Bishop WP. Ulcerative colitis complicated by ischemic colitis and Budd Chiari syndrome. J Pediatr Gastroenterol Nutr. 2005;40(1):94–7.

    PubMed  Google Scholar 

  199. Socha P, Ryzko J, Janczyk W, Dzik E, Iwanczak B, Krzesiek E. Hepatic vein thrombosis as a complication of ulcerative colitis in a 12-year-old patient. Dig Dis Sci. 2007;52(5):1293–8.

    PubMed  Google Scholar 

  200. Magrì S, Paduano D, Chicco F, Cingolani A, Farris C, Delogu G, et al. Nonalcoholic fatty liver disease in patients with inflammatory bowel disease: beyond the natural history. World J Gastroenterol. 2019;25(37):5676–86.

    PubMed  PubMed Central  Google Scholar 

  201. Principi M, Iannone A, Losurdo G, Mangia M, Shahini E, Albano F, et al. Nonalcoholic fatty liver disease in inflammatory bowel disease: prevalence and risk factors. Inflamm Bowel Dis. 2018;24(7):1589–96.

    PubMed  Google Scholar 

  202. Sartini A, Gitto S, Bianchini M, Verga MC, Di Girolamo M, Bertani A, et al. Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease. Cell Death Dis. 2018;9(2):87.

    PubMed  PubMed Central  Google Scholar 

  203. Saubermann LJ, Deneau M, Falcone RA, Murray KF, Ali S, Kohli R, et al. Hepatic issues and complications associated with inflammatory bowel disease: a clinical report from the NASPGHAN inflammatory bowel disease and hepatology committees. J Pediatr Gastroenterol Nutr. 2017;64(4):639–52.

    PubMed  Google Scholar 

  204. Greenstein AJ, Sachar DB, Panday AK, Dikman SH, Meyers S, Heimann T, et al. Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients. Medicine. 1992;71(5):261–70.

    CAS  PubMed  Google Scholar 

  205. Serra I, Oller B, Mañosa M, Naves JE, Zabana Y, Cabré E, et al. Systemic amyloidosis in inflammatory bowel disease: retrospective study on its prevalence, clinical presentation, and outcome. J Crohns Colitis. 2010;4(3):269–74.

    PubMed  Google Scholar 

  206. 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(4):295–300.

    CAS  PubMed  Google Scholar 

  207. Sattianayagam PT, Gillmore JD, Pinney JH, Gibbs SD, Wechalekar AD, Gilbertson JA, et al. Inflammatory bowel disease and systemic AA amyloidosis. Dig Dis Sci. 2013;58(6):1689–97.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada

    Rebecca Little, Binita M. Kamath & Amanda Ricciuto

  2. University of Toronto, Toronto, ON, Canada

    Binita M. Kamath & Amanda Ricciuto

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  1. Rebecca Little
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  2. Binita M. Kamath
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  3. Amanda Ricciuto
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Correspondence to Amanda Ricciuto .

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Editors and Affiliations

  1. Division of GI, Hepatology & Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Petar Mamula

  2. Division of GI, Hepatology & Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Judith R. Kelsen

  3. Division of GI, Hepatology & Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Andrew B. Grossman

  4. Division of GI, Hepatology & Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Robert N. Baldassano

  5. Division of Pediatric Gastroenterology, Prisma Health Children’s Hospital—Upstate, Greenville, SC, USA

    Jonathan E. Markowitz

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Little, R., Kamath, B.M., Ricciuto, A. (2023). Liver Disease in Pediatric Inflammatory Bowel Disease. In: Mamula, P., Kelsen, J.R., Grossman, A.B., Baldassano, R.N., Markowitz, J.E. (eds) Pediatric Inflammatory Bowel Disease. Springer, Cham. https://doi.org/10.1007/978-3-031-14744-9_11

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