Autoimmune Liver Disease
Therapeutic Strategies for Autoimmune HepatitisManns M.P. · Strassburg C.P.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Autoimmune hepatitis (AIH) is a disease of unknown etiology. However, a loss of tolerance against the patient’s own liver is regarded as the main pathogenetic mechanism. Immunosuppressive therapy prolongs survival in patients with severe AIH. Two phases of therapy have to be distinguished. In newly diagnosed AIH, induction of remission is the main goal. Here predniso(lo)ne alone or in combination with azathioprine has been shown to induce remission in the majority of patients. In the past, reduction of aminotransferase levels below two times the upper limit of normal was the aim of therapy. Nowadays, normalization of aminotransferase levels should be achieved. The majority of patients usually respond to therapy within 6–12 months. A significant reduction in aminotransferase levels is achieved within a few weeks of therapy. Improvement in clinical symptoms is followed by improvement in biochemical parameters of disease activity and then by significant improvement in histological disease activity. Around 20–40% of patients do not achieve remission. In these patients, alternative therapies should be evaluated for the individual patient. Prospective controlled trials with a larger number of patients are missing in this population. At the moment, mycophenolate mofetil at a dose of 2 × 1 g daily, either given alone or in combination with predniso(lo)ne, is able to achieve remission in a significant proportion of patients. Based on recent retrospective observations, mycophenolate mofetil is beneficial in patients who were previously azathioprine intolerant rather than azathioprine failure patients. Again, prospective trials are missing. Alternative drugs include cyclophosphamide, cyclosporin A, tacrolimus and others. Women in particular suffer from steroid-specific side effects, including weight gain, moon face, diabetes, glaucoma and bone disease. Recently, a topical steroid, budesonide, was shown to induce disease remission in combination with azathioprine. The second phase of therapy is maintenance of remission with the lowest possible dose in order to maintain remission while preventing significant side effects. Careful evaluation of the individual patients should lead to the decision whether predniso(lo)ne, budesonide, azathioprine or a combination of one of the steroids with azathioprine is to be used to maintain remission. Recently, a study has shown that after 6 months of induction therapy with prednisone plus azathioprine, a switch to budesonide in combination with azathioprine reduced steroid-specific side effects while maintaining remission of liver disease. Therefore, the application of the topical steroids may be helpful in maintaining remission while reducing steroid-specific side effects. Patients with liver cirrhosis should not be treated with budesonide since the benefit of budesonide with its 90% pass effect in the liver is lost if the patient has already developed portal hypertension with significant portosystemic shunting. Furthermore, there are safety concerns regarding budesonide use in cirrhotic patients derived from studies in primary biliary cirrhosis. If the diagnosis is correct and the appropriate therapy is chosen, liver transplantation should be avoidable in patients with AIH.
© 2011 S. Karger AG, Basel
- International Autoimmune Hepatitis Group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999;31:929–938.
- Czaja AJ, Manns MP: Advances in the diagnosis, pathogenesis, and management of autoimmune hepatitis. Gastroenterology 2010;139:58–72.e4.
- Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, Vierling JM: AASLD Practice Guidelines: diagnosis and management of autoimmune hepatitis. Hepatology 2010;51:2193–2213.
- Hennes EM, Zeniya M, Czaja AJ, Pares A, Dalekos GN, Krawitt EL, Bittencourt PL, Porta G, Boberg KM, Hofer H, Bianchi FB, Shibata M, Schramm C, Eisenmann de Torres B, Galle PR, McFarlane I, Dienes HP, Lohse AW: Simplified diagnostic criteria for autoimmune hepatitis. Hepatology 2008;48:169–176.
- Czaja AJ, Lindor KD: Failure of budesonide in a pilot study of treatment-dependent autoimmune hepatitis. Gastroenterology 2000;119:1312–1316.
- Summerskill WH, Kormann MG, Ammon HV, Baggenstoss AH: Prednisone for chronic active liver disease: dose titration, standard dose and combination with azathioprine compound. Gut 1975;16:876–883.
- Manns MP, Woynarowski M, Kreisel W, Lurie Y, Rust C, Zuckerman E, Bahr MJ, Günther R, Hultcrantz RW, Spengler U, Lohse AW, Szalay F, Farkkilä M, Proels M, Strassburg CP, European AIH-BUC-Study Group: Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. Gastroenterology 2010;139:1198–1206.
- Stellon AJ, Hegarty JE, Portmann B, Williams R: Randomized controlled trial of azathioprine withdrawal in autoimmune chronic active hepatitis. Lancet 1985;1:668–670.
Manns MP, Strassburg CP: Autoimmune hepatitis; in O’ Grady JG, Lake JR, Howdle DP (eds): Comprehensive Clinical Hepatology. London, Mosby, 2000, vol 16, pp 1–14.
- Johnson PJ, McFarlane IG, Williams R: Azathioprine for long-term maintenance of remission in autoimmune hepatitis. N Engl J Med 1995;333:958–963.
- Malekzadeh R, Nasseri-Moghaddam S, Kaviani MJ, Taheri H, Kamalian N, Sotoudeh M: Cyclosporine A is a promising alternative to corticosteroids in autoimmune hepatitis. Dig Dis Sci 2001;46:1321–1327.
- Alvarez F, Ciocca M, Canero-Velasco C, Ramonet M, de Davila MT, Cuarterolo M, Gonzalez T, Jara-Vega P, Camarena C, Brochu P, Drut R, Alvarez E: Short-term cyclosporine induces a remission of autoimmune hepatitis in children. J Hepatol 1999;30:222–227.
- Danielsson A, Prytz H: Oral budesonide for treatment of autoimmune chronic active hepatitis. Aliment Pharmacol Ther 1994;8:585–590.
Schüler A, Manns MP: Treatment of autoimmune hepatitis; in Arroyo V, Bosch J, Rodes J (eds): Treatment in Hepatology. Paris, Masson, 1995, pp 375–383.
- Wiegand J, Schüler A, Kanzler S, Lohse A, Beuers U, Kreisel W, Spengler U, Koletzko S, Jansen PL, Hochhaus G, Möllmann HW, Pröls M, Manns MP: Budesonide in previously untreated autoimmune hepatitis. Liver Int 2005;25:927–934.
- Richardson PD, James PD, Ryder SD: Mycophenolate mofetil for maintenance of remission in autoimmune hepatitis in patients resistant to or intolerant of azathioprine. J Hepatol 2000;33:371–375.
- Chatur N, Ramji A, Bain VG, Ma MM, Marotta PJ, Ghent CN, Lilly LB, Heathcote EJ, Deschenes M, Lee SS, Steinbrecher UP, Yoshida EM: Transplant immunosuppressive agents in non-transplant chronic autoimmune hepatitis: the Canadian Association for the Study of the Liver (CASL) experience with mycophenolate mofetil and tacrolimus. Liver Int 2005;25:723–727.
- Hennes EM, Oo YH, Schramm C, et al: Mycophenolate mofetil as second line therapy in autoimmune hepatitis? Am J Gastroenterol 2008;103:3063–3070.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.