Autoimmune hepatitis (AIH) is an uncommon though serious and potentially life-threatening disease which requires prompt recognition and treatment. In cases unresponsive to conventional treatment, achieving disease remission can be difficult. Keeping this in background in this study a comparision has been made between Budesonide combination with that of immunosuppressant i.e cyclosporine  in treatment of Autoimmune Hepatitis.

Methods: 30 AIH patients were included in this study. All patients were divided into two groups i.e group A and B.15 patients Group A were treated with Budesonide 9mg/kg/day with Azathioprine 2mg/kg/day and 15 patients Group B were treated with Cyclosporine 3mg/kg/day. All the drugs were administered for 6 months.

Result: All the patients with Budesonide and Azathioprine therapy were found to Antinuclear antibody negative after 6 months and more than 10 patients of Group A were found to have decrease in level of AST and ALT after 6 months. In patients with Cyclosporine therapy only 9 patients were found to be ANA negative after 6 months. Less than 10 patients were found to have decrease in levels of AST and ALT after 6 months in group B.

Conclusion: Group A patients demonstrated a good biochemical response after 6 months of therapy in comparision to Group B patients. From this it is concluded that patients with Budesonide and Azathioprine therapy shows a significant improvement in AIH after 6 months in comparision to Cyclosporine therapy.

Keywords: Autoimmune Hepatitis, Budesonide, Azathioprine, Cyclosporine, Alanine aminotransferrase, Aspartate aminotransferase, Antinuclear Antibody, Immunosupressant.

1. Floreani P, Restrepo-Jimenez, M.F. Secchi et al,” Etiopathogenesis of autoimmune hepatitis”, Journal of Autoimmunity,vol 95,pp.133-143,2018.
2. J. Czaja,”Diagnosis and management of autoimmune hepatitis: current status and future directions,” Gut Liver, vol.10, no.2,pp.177-203,2016.
3. Vergani D, Mieli-Vergani G. Pharmacological management of autoimmune hepatitis. Expert Opin Pharmacother 2011;12:607-613.
4. A. Heneghan, A.D.Yeoman, S.Verma, A.D. Smith and M.S. Longhi,” Autoimmune hepatitis,” Lancet, vol.382, no.9902, pp.1433-1444,2013.
5. Vento,T.Garofano, G.Di Perri, L.Dolci, E. Concia, and D. Bassetti,” Identification of hepatitis A virus as a trigger for autoimmune chronic hepatitis type 1 in susceptible individuals,” The Lancet, vol .337,no.8751,pp.1183-1187,1991.
6. Vento, F.Cainelli, C. Renzini, E.Concia,” Autoimmune hepatitis type 2 induced by HCV and persisting after viral clearance,”Lancet,vol.350,no.9087,pp.1298-1299,1997.
7. Le Cann, M.J.Tong, J.Werneke, and P. Coursaget,” Detection of antibodies to hepatitis E virus in patients with autoimmune chronic active hepatitis and primary billiary cirrhosis,” Scandinavian Journal of Gastroenterology, vol.32,no.4 pp.387-389,1997.
8. Vento,L.F.Cainelli,T.Ferraro,and E.Concia,” Autoimmune hepatitis type 1 after measles,” The American Journal of Gastroenterology, vol. 91,no.12,pp.2618-2620,1996.
9. Vento, L.Guella, F.Mirandola, F.Cainelli, G. Di Perri, M.Solbiati et.al.,” Epstein-Barr virus as a trigger for autoimmune hepatitis in susceptible individuals,” Lancet, vol.346, no.8975, pp.608-609,1995.
10. P.Manns,”Viruses and autoimmune liver disease,”Inter-virology, vol.35,no.1-4,pp. 108-115,1993.
11. Licata, M.Maida, D.Cabiba et al.,”Clinical features and outcomes of patients with drug-induced autoimmune hepatitis: a retrospective cohort study,” Digestive and liver Disease, vol.46, no.12, pp.1116-1120,2014.
12. European Association for study of the Liver. EASL clinical practice guidelines: Autoimmune hepatitis.J Hepatol 2015;63:971-1004.
13. Gleeson D, Heneghan MA. British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis.Gut 2011;60:1611-1629.
14. Bogdanos DP, Mieli-Vergani G, Vergani D, Autoantibodies and their antigens in autoimmune hepatitis. Semin Liver Dis 2009;29:241-253.
15. Liberal R, Mieli-Vergani G,Vergani D. Clinical significance of autoantibodies in autoimmune hepatitis.J Autoimmune 2013;46:17-24.
16. Washington MK. Autoimmune liver disease: overlap and outliers. Mod Pathol 2007;20(Suppl 1):515-530.
17. Manns MP, Czaja AJ, Gorham JD, Krawitt EL et al. Diagnosis and management of Autoimmune hepatitis. Hepatology 2010;51:2193-2213.
18. Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999;31:929-938.)
19. Vergani D, Mackay IR, Mieli-Vergani G. The Autoimmune Disease(Fifth Edition). Boston Academic Press;2014.p 889-907.
20. Alvarez F, Berg PA, Bianchi FB et al.I nternational Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999;31:929-938.
21. Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008;48:169-176.
22. Czaja AJ. Performance parameters of the diagnostic Scoring systems for autoimmune hepatitis. Hepatology 2008;48:1540-1548.
23. Manns MP, Czaja AJ, Gorham JD,et al. Diagnosis and management of autoimmune hepatitis.Hepatology.2010;51:2193-2213.
24. Mackay IR. Historical reflections on autoimmune hepatitis. World J Gastroenterol.2008;14:3292-3300.
25. Peiseler M, Liebscher T, Sebode M, et al, Efficacy and limitations of budesonide as a second-line treatment for patients with autoimmune hepatitis. Clin Gastroenterol Hepatol.2018;16(260-267).
26. Zachou K, Gatselis NK. Arvaniti P.et al.A real-world study focused on the long-term efficacy of mycophenolate mofetil as first-line treatment of autoimmune hepatitis. Aliment Pharmacol Ther. 2016;43:1035-1047.
27. Efe C, Hagstrom H, Ytting H,et al. Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis. Clin Gastroenterol Hepatol. 2017;15(1950-1956).
28. Than NN, Wiegard C, Weiler-Normann C, et al. Long-term follow-up of patients with difficult to treat type 1 autoimmune hepatitis on Tacrolimus therapy.ScandJ Gastroenterol.2016;51:329-336.
29. European Association for the study of the liver. EASL clinical practice guidelines: autoimmune hepatitis .J Hepatol.2015;63:971-1004.
30. Czaja A J.Safety issues in the management of autoimmune hepatitis. Expert Opin Drug Saf.2008:7:319-333.
31. Yeoman AD,Westbrook RH,Zen Y,et al.Early predictors of corticosteroid treatment failure in icteric presentations of autoimmune hepatitis.Hepatology.2011;53:926-934.
32. Danielsson A,Prytz H. Oral budesonide for treatment of autoimmune chronic active hepatitis. Aliment Pharmacol Ther 1994;8:585-590.
33. Manns MP, Czaja AJ, Gorham JD, et al.Diagnosis and management of autoimmune hepatitis. Hepatology 2010;51:2193-2213.
34. Czaja AJ. Current and prospective pharmacotherapy for autoimmune hepatitis. Expert Opin Pharmacother 2014;15:1715-1736.
35. 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;139:1198-1206.
36. Malekzadeh R, Nasseri-Moghaddam S,Kaviani MJ, Taheri H, Kamalian N, Sotoudeh M. Cyclosporin A is a promising alternative to corticosteroids in autoimmune hepatitis.Dig Dis Sci 2001;46:1321-1327.
37. Czaja AJ. Drug choices in autoimmune hepatitis. Part B:nonsteroids. Expert Rev Gastroenterol Hepatol 2012;6:617-635.
38. A Furukawa, S.A. Wisel, and Q Tang,” Impact of immunomodulatory drugs on regulatory T cell,” Transplantation, vol.100.no.11, pp.2288-2300,2016.
39. 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 Gastroent-erol.2003;9:2681-2685.
40. Hempfling W, Grunhage F, Dilger K, Reichel C, Beuers U, Sauerbruch T. Pharmacokinetics and Pharmacodynamic action of budesonide in early and late stage primary biliary cirrhosis .Hepatology.2003;38;196-202.
41. Czaja AJ. Safety issues in the management of autoimmune hepatitis. Expert Opin Drug Saf.2008;319-333.
42. .Yeoman AD, Westbrook RH, Zen Y, et al. Early predictors of corticosteroid treatment failure in icteric presentations of autoimmune hepatitis.Hepatology.2011;53:926-934.
43. Alvarez F, Ciocca M, Canero-Velasco C, Ramonet M et al. Short-term cyclosporine induces a remission of autoimmune hepatitis in children. J Hepatol 1999;30:222-227.

Rasmirekha Behera

Dept of Pharmacology I.M.S & SUM Hospital Bhubaneswar, India