• 1
    Edward V, Loftus J. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology. 2004; 126: 15041517.
  • 2
    Lichtenstein GR, Hanauer SB, Sandborn WJ, et al. Management of Crohn's disease in adults. Am J Gastroenterol. 2009; 104: 465483; quiz 464, 484.
  • 3
    Katzung BG. Basic and Clinical Pharmacology. 9th ed. New York: McGraw-Hill; 2004: 907908.
  • 4
    Kozarek RA, Patterson DJ, Gelfand MD, et al. Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med. 1989; 110: 353356.
  • 5
    Amital H, Arnson Y, Chodick G, et al. Hepatotoxicity rates do not differ in patients with rheumatoid arthritis and psoriasis treated with methotrexate. Rheumatology (Oxford). 2009; 48: 11071110.
  • 6
    Kalb RE, Strober B, Weinstein G, et al. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol. 2009; 60: 824837.
  • 7
    Visser K, Katchamart W, Loza E, et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E initiative. Ann Rheum Dis. 2009; 68: 10861093.
  • 8
    Fournier MR, Klein J, Minuk GY, et al. Changes in liver biochemistry during methotrexate use for inflammatory bowel disease. Am J Gastroenterol. 2010; 105: 16201626.
  • 9
    Bénichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol. 1990; 11: 272276.
  • 10
    Lémann M, Zenjari T, Bouhnik Y, et al. Methotrexate in Crohn's disease: long-term efficacy and toxicity. Am J Gastroenterol. 2000; 95: 17301734.
  • 11
    Arora S, Katkov W, Cooley J, et al. Methotrexate in Crohn's disease: results of a randomized, double-blind, placebo-controlled trial. Hepatogastroenterology. 1999; 46: 17241729.
  • 12
    Ardizzone S, Bollani S, Manzionna G, et al. Comparison between methotrexate and azathioprine in the treatment of chronic active Crohn's disease: a randomised, investigator-blind study. Dig Liver Dis. 2003; 35: 619627.
  • 13
    Baron TH, Truss CD, Elson CO. Low-dose oral methotrexate in refractory inflammatory bowel disease. Dig Dis Sci. 1993; 38: 18511856.
  • 14
    Egan LJ, Sandborn WJ, Tremaine WJ, et al. A randomized dose-response and pharmacokinetic study of methotrexate for refractory inflammatory Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther. 1999; 13: 15971604.
  • 15
    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: 292297.
  • 16
    Maté-Jiménez J, Hermida C, Cantero-Perona J, et al. 6-mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid-dependent inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2000; 12: 12271233.
  • 17
    Oren R, Arber N, Odes S, et al. Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial. Gastroenterology. 1996; 110: 14161421.
  • 18
    Oren R, Moshkowitz M, Odes S, et al. Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial. Am J Gastroenterol. 1997; 92: 22032209.
  • 19
    Paoluzi OA, Pica R, Marcheggiano A, et al. Azathioprine or methotrexate in the treatment of patients with steroid-dependent or steroid-resistant ulcerative colitis: results of an open-label study on efficacy and tolerability in inducing and maintaining remission. Aliment Pharmacol Ther. 2002; 16: 17511759.
  • 20
    Schröder O, Blumenstein I, Schulte-Bockholt A, et al. Combining infliximab and methotrexate in fistulizing Crohn's disease resistant or intolerant to azathioprine. Aliment Pharmacol Ther. 2004; 19: 295301.
  • 21
    Schröder O, Blumenstein I, Stein J. Combining infliximab with methotrexate for the induction and maintenance of remission in refractory Crohn's disease: a controlled pilot study. Eur J Gastroenterol Hepatol. 2006; 18: 1116.
  • 22
    Szklo M, Nieto F. Epidemiology: Beyond the Basics. Madison, WI: Jones and Bartlett; 2007.
  • 23
    Sutton A. Methods for Meta-analysis in Medical Research. West Sussex, UK: John Wiley & Sons; 2000.
  • 24
    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21: 15391558.
  • 25
    Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009; 62: 10061012.
  • 26
    Edward VLJ, William JS, Keith DL, et al. Interactions between chronic liver disease and inflammatory bowel disease. Inflamm Bowel Dis. 1997; 3: 288302.
  • 27
    Mendes FD, Levy C, Enders FB, et al. Abnormal hepatic biochemistries in patients with inflammatory bowel disease. Am J Gastroenterol. 2007; 102: 344350.
    Direct Link:
  • 28
    Kremer JM, Alarcón GS, Lightfoot RW, et al. Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum. 1994; 37: 316328.
  • 29
    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: 31503156.
    Direct Link:
  • 30
    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: 15181527.
    Direct Link:
  • 31
    Bastida G, Nos P, Aguas M, et al. Incidence, risk factors and clinical course of thiopurine-induced liver injury in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2005; 22: 775782.
  • 32
    Hindorf U, Lindqvist M, Hildebrand H, et al. Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2006; 24: 331342.