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Treating the Adult Patient: First Line Therapy

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Diagnosis and Management of Autoimmune Hepatitis

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Abstract

First-line therapy for autoimmune hepatitis (AIH) centers around initiation of predniso(lo)ne followed by the introduction of azathioprine to maintain a biochemical remission. Combination therapy during induction with subsequent tapering of steroids with the intent of maintaining remission with azathioprine monotherapy is the goal. A majority of patients with AIH are capable of attaining a remission with first-line therapy and can be cautiously considered for withdrawal of therapy following 3 years of therapy and after at least 2 years of normal transaminase and IgG levels. Relapse following tapering or after discontinuation of therapy is highly likely, and therefore requires close monitoring and timely resumption of therapy. Individualizing treatment to achieve a balance between maximizing the benefits of therapy while limiting toxicities is the foundation of first-line therapy for AIH.

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References

  1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: autoimmune hepatitis. J Hepatol. 2015;63(4):971–1004.

    Article  Google Scholar 

  2. De Groote J, Fevery J, Lepoutre L. Long-term follow-up of chronic active hepatitis of moderate severity. Gut. 1978;19(6):510–3.

    Article  Google Scholar 

  3. Czaja AJ. Features and consequences of untreated type 1 autoimmune hepatitis. Liver Int. 2009;29(6):816–23.

    Article  CAS  Google Scholar 

  4. Feld JJ, Dinh H, Arenovich T, Marcus VA, Wanless IR, Heathcote EJ. Autoimmune hepatitis: effect of symptoms and cirrhosis on natural history and outcome. Hepatology. 2005;42(1):53–62.

    Article  Google Scholar 

  5. Cook GC, Mulligan R, Sherlock S. Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. Q J Med. 1971;40(158):159–85.

    Article  CAS  Google Scholar 

  6. Soloway RD, Summerskill WH, Baggenstoss AH, Geall MG, Gitnick GL, Elveback IR, et al. Clinical, biochemical, and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis. Gastroenterology. 1972;63(5):820–33.

    Article  CAS  Google Scholar 

  7. Lamers MM, van Oijen MG, Pronk M, Drenth JP. Treatment options for autoimmune hepatitis: a systematic review of randomized controlled trials. J Hepatol. 2010;53(1):191–8.

    Article  CAS  Google Scholar 

  8. Schramm C, Weiler-Normann C, Wiegard C, Hellweg S, Muller S, Lohse AW. Treatment response in patients with autoimmune hepatitis. Hepatology. 2010;52(6):2247–8.

    Article  Google Scholar 

  9. Montano-Loza AJ, Carpenter HA, Czaja AJ. Improving the end point of corticosteroid therapy in type 1 autoimmune hepatitis to reduce the frequency of relapse. Am J Gastroenterol. 2007;102(5):1005–12.

    Article  CAS  Google Scholar 

  10. Stellon AJ, Keating JJ, Johnson PJ, McFarlane IG, Williams R. Maintenance of remission in autoimmune chronic active hepatitis with azathioprine after corticosteroid withdrawal. Hepatology. 1988;8(4):781–4.

    Article  CAS  Google Scholar 

  11. Johnson PJ, McFarlane IG, Williams R. Azathioprine for long-term maintenance of remission in autoimmune hepatitis. N Engl J Med. 1995;333(15):958–63.

    Article  CAS  Google Scholar 

  12. Hartl J, Denzer U, Ehlken H, Zenouzi R, Peiseler M, Sebode M, et al. Transient elastography in autoimmune hepatitis: timing determines the impact of inflammation and fibrosis. J Hepatol. 2016;65(4):769–75.

    Article  Google Scholar 

  13. Hartl J, Ehlken H, Sebode M, Peiseler M, Krech T, Zenouzi R, et al. Usefulness of biochemical remission and transient elastography in monitoring disease course in autoimmune hepatitis. J Hepatol. 2018;68(4):754–63.

    Article  Google Scholar 

  14. Thalen A, Brattsand R. Synthesis and anti-inflammatory properties of budesonide, a new non-halogenated glucocorticoid with high local activity. Arzneimittelforschung. 1979;29(11):1687–90.

    CAS  PubMed  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. Manns MP, Jaeckel E, Taubert R. Budesonide in autoimmune hepatitis: the right drug at the right time for the right patient. Clin Gastroenterol Hepatol. 2018;16(2):186–9.

    Article  Google Scholar 

  17. Peiseler M, Liebscher T, Sebode M, Zenouzi R, Hartl J, Ehlken H, et al. Efficacy and limitations of budesonide as a second-line treatment for patients with autoimmune hepatitis. Clin Gastroenterol Hepatol. 2018;16(2):260–7. e1.

    Article  CAS  Google Scholar 

  18. Geier A, Gartung C, Dietrich CG, Wasmuth HE, Reinartz P, Matern S. Side effects of budesonide in liver cirrhosis due to chronic autoimmune hepatitis: influence of hepatic metabolism versus portosystemic shunts on a patient complicated with HCC. World J Gastroenterol. 2003;9(12):2681–5.

    Article  Google Scholar 

  19. Efe C, Ozaslan E, Kav T, Purnak T, Shorbagi A, Ozkayar O, et al. Liver fibrosis may reduce the efficacy of budesonide in the treatment of autoimmune hepatitis and overlap syndrome. Autoimmun Rev. 2012;11(5):330–4.

    Article  CAS  Google Scholar 

  20. Karkhanis J, Verna EC, Chang MS, Stravitz RT, Schilsky M, Lee WM, et al. Steroid use in acute liver failure. Hepatology. 2014;59(2):612–21.

    Article  CAS  Google Scholar 

  21. Ichai P, Duclos-Vallee JC, Guettier C, Hamida SB, Antonini T, Delvart V, et al. Usefulness of corticosteroids for the treatment of severe and fulminant forms of autoimmune hepatitis. Liver Transpl. 2007;13(7):996–1003.

    Article  Google Scholar 

  22. Yeoman AD, Westbrook RH, Zen Y, Bernal W, Al-Chalabi T, Wendon JA, et al. Prognosis of acute severe autoimmune hepatitis (AS-AIH): the role of corticosteroids in modifying outcome. J Hepatol. 2014;61(4):876–82.

    Article  CAS  Google Scholar 

  23. Anastasiou OE, Dogan-Cavus B, Kucukoglu O, Baba H, Kahraman A, Gerken G, et al. Corticosteroid therapy improves the outcome of autoimmune hepatitis-induced acute liver failure. Digestion. 2018;98(2):104–11.

    Article  CAS  Google Scholar 

  24. Tan P, Marotta P, Ghent C, Adams P. Early treatment response predicts the need for liver transplantation in autoimmune hepatitis. Liver Int. 2005;25(4):728–33.

    Article  Google Scholar 

  25. Miyake Y, Iwasaki Y, Terada R, Okamaoto R, Ikeda H, Makino Y, et al. Persistent elevation of serum alanine aminotransferase levels leads to poor survival and hepatocellular carcinoma development in type 1 autoimmune hepatitis. Aliment Pharmacol Ther. 2006;24(8):1197–205.

    Article  CAS  Google Scholar 

  26. Verma S, Gunuwan B, Mendler M, Govindrajan S, Redeker A. Factors predicting relapse and poor outcome in type I autoimmune hepatitis: role of cirrhosis development, patterns of transaminases during remission and plasma cell activity in the liver biopsy. Am J Gastroenterol. 2004;99(8):1510–6.

    Article  Google Scholar 

  27. Hoeroldt B, McFarlane E, Dube A, Basumani P, Karajeh M, Campbell MJ, et al. Long-term outcomes of patients with autoimmune hepatitis managed at a nontransplant center. Gastroenterology. 2011;140(7):1980–9.

    Article  Google Scholar 

  28. Czaja AJ. Rapidity of treatment response and outcome in type 1 autoimmune hepatitis. J Hepatol. 2009;51(1):161–7.

    Article  CAS  Google Scholar 

  29. Czaja AJ, Menon KV, Carpenter HA. Sustained remission after corticosteroid therapy for type 1 autoimmune hepatitis: a retrospective analysis. Hepatology. 2002;35(4):890–7.

    Article  CAS  Google Scholar 

  30. Hegarty JE, Nouri Aria KT, Portmann B, Eddleston AL, Williams R. Relapse following treatment withdrawal in patients with autoimmune chronic active hepatitis. Hepatology. 1983;3(5):685–9.

    Article  CAS  Google Scholar 

  31. van Gerven NM, Verwer BJ, Witte BI, van Hoek B, Coenraad MJ, van Erpecum KJ, et al. Relapse is almost universal after withdrawal of immunosuppressive medication in patients with autoimmune hepatitis in remission. J Hepatol. 2013;58(1):141–7.

    Article  Google Scholar 

  32. Hartl J, Ehlken H, Weiler-Normann C, Sebode M, Kreuels B, Pannicke N, et al. Patient selection based on treatment duration and liver biochemistry increases success rates after treatment withdrawal in autoimmune hepatitis. J Hepatol. 2015;62(3):642–6.

    Article  CAS  Google Scholar 

  33. Cuffari C, Dassopoulos T, Turnbough L, Thompson RE, Bayless TM. Thiopurine methyltransferase activity influences clinical response to azathioprine in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2004;2(5):410–7.

    Article  CAS  Google Scholar 

  34. Ben Ari Z, Mehta A, Lennard L, Burroughs AK. Azathioprine-induced myelosuppression due to thiopurine methyltransferase deficiency in a patient with autoimmune hepatitis. J Hepatol. 1995;23(3):351–4.

    CAS  PubMed  Google Scholar 

  35. Lennard L, Van Loon JA, Weinshilboum RM. Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther. 1989;46(2):149–54.

    Article  CAS  Google Scholar 

  36. Gardiner SJ, Gearry RB, Begg EJ, Zhang M, Barclay ML. Thiopurine dose in intermediate and normal metabolizers of thiopurine methyltransferase may differ three-fold. Clin Gastroenterol Hepatol. 2008;6(6):654–60; quiz 04.

    Article  CAS  Google Scholar 

  37. Langley PG, Underhill J, Tredger JM, Norris S, McFarlane IG. Thiopurine methyltransferase phenotype and genotype in relation to azathioprine therapy in autoimmune hepatitis. J Hepatol. 2002;37(4):441–7.

    Article  CAS  Google Scholar 

  38. Czaja AJ, Carpenter HA. Thiopurine methyltransferase deficiency and azathioprine intolerance in autoimmune hepatitis. Dig Dis Sci. 2006;51(5):968–75.

    Article  CAS  Google Scholar 

  39. Pratt DS, Flavin DP, Kaplan MM. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology. 1996;110(1):271–4.

    Article  CAS  Google Scholar 

  40. Dhaliwal HK, Anderson R, Thornhill EL, Schneider S, McFarlane E, Gleeson D, et al. Clinical significance of azathioprine metabolites for the maintenance of remission in autoimmune hepatitis. Hepatology. 2012;56(4):1401–8.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Hepatology, Carolinas Medical Center-Atrium Health, Charlotte, NC, USA

    Andrew S. deLemos

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  1. Andrew S. deLemos
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Correspondence to Andrew S. deLemos .

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  1. Carolinas Medical Center-Atrium Health, University of North Carolina School of Medicine, Charlotte, NC, USA

    Mark W. Russo

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deLemos, A.S. (2020). Treating the Adult Patient: First Line Therapy. In: Russo, M. (eds) Diagnosis and Management of Autoimmune Hepatitis. Springer, Cham. https://doi.org/10.1007/978-3-030-33628-8_5

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  • DOI: https://doi.org/10.1007/978-3-030-33628-8_5

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-33627-1

  • Online ISBN: 978-3-030-33628-8

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