Long-term management and prognosis of autoimmune hepatitis (AIH): A single center experience

 

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Summary

Background: Controlled trials have firmly established the need for immunosuppressive therapy in autoimmune hepatitis. However, reports about long-term management and prognosis of the disease are scarce.

Patients and methods: We reviewed the charts of 103 consecutive patients with a well-documented long-term course of autoimmune hepatitis who had been carefully managed over a mean observation period of 95 months (12-405 months).

Results: Under immunosuppressive therapy 94 patients (91.2 %) reached complete remission after a mean treatment duration of 3 ± 3 months. 28 of the 103 patients (27.2 %) were eligible for a trial of treatment withdrawal after a mean treatment duration of 32.2 months (range: 12-81 months). 21 of these patients (75 %) had a relapse following treatment withdrawal. 13.6 % of patients had intolerance of or severe side effects to azathioprine. There was no increase in tumor risk during a cumulative observation period of 423 patient-years of azathioprine therapy. Corticosteroid side effects occurred mostly during induction therapy, but were usually minor and resolved upon dose reduction. During a cumulative observation period of 842 patient-years no liver related deaths occurred and no patient had to be referred to liver transplantation, even though 30 patients (29.1 %) had histological evidence of cirrhosis at presentation. The overall 5- and 10-year survival of patients with autoimmune hepatitis was identical to an age- and sex-matched control population.

Conclusion: Our study shows that the majority of patients with AIH do achieve a complete remission within 3 months, but require long-term or permanent immunosuppressive therapy that is usually well tolerated. Long-term survival in well-managed patients is excellent.

Management und Prognose der autoimmunen Hepatitis: Erfahrungen eines Zentrums

Einleitung: Kontrollierte Studien belegen den Wert einer immunsuppressiven Therapie zur Behandlung der autoimmunen Hepatitis. Allerdings liegen nur wenige Berichte über Langzeitverläufe und Prognose dieser Erkrankung vor.

Patienten und Methodik: Die Krankenakten von 103 konsekutiven Patienten mit lückenlos dokumentiertem Verlauf einer autoimmunen Hepatitis, die wir über eine mittlere Beobachtungszeit von 95 Monaten (12-405 Monaten) betreuten, wurden ausgewertet.

Ergebnisse: 94 Patienten (91,2 %) erreichten unter immunsuppressiver Therapie eine komplette Remission innerhalb von 3 ± 3 Monaten. Bei 28 Patienten (27,2 %) wurde nach einer mittleren Behandlungsdauer von 32,2 Monaten die immunsuppressive Therapie schrittweise beendet. 21 dieser Patienten (75 %) hatten ein Rezidiv der autoimmunen Hepatitis. 14 Patienten (13,6 %) konnten aufgrund von Unverträglichkeit oder Nebenwirkungen nicht mit Azathioprin behandelt werden. Während einer kumulativen Beobachtungsdauer von 423 Patientenjahren unter Azathioprintherapie beobachteten wir kein signifikant erhöhtes Tumorrisiko. Nebenwirkungen auf Kortikosteroide traten meist während der Induktionsphase auf, waren jedoch meist geringfügig und reversibel nach Dosisreduktion. Obwohl bereits 30 Patienten (29,1 %) bei Diagnosestellung eine Leberzirrhose aufwiesen, traten während einer kumulativen Beobachtungszeit von 842 Patientenjahren keine Todesfälle als Komplikation der Lebererkrankung auf. Kein Patient musste lebertransplantiert werden. Das 5- und 10-Jahres-Überleben unterschied sich nicht von dem eines Kontrollkollektivs.

Schlussfolgerungen: Die Mehrzahl der Patienten mit autoimmuner Hepatitis erreicht innerhalb der ersten 3 Monate nach Therapiebeginn eine komplette Remission. Allerdings ist meist eine Langzeittherapie notwendig, die als niedrig dosierte Kombinationstherapie gut vertragen wird. Die Langzeitprognose von Patienten mit autoimmuner Hepatitis ist bei entsprechender Patientenführung exzellent.

References

• 1 Krawitt E L. Autoimmune hepatitis.  N Engl J Med. 1996;  334 897-903
  Google Scholar
• 2 Czaja A J. Autoimmune hepatitis: Evolving concepts and treatment strategies.  Dig Dis Sci. 1995;  40 435-456
  Google Scholar
• 3 Obermayer-Straub P, Strassburg C P, Manns M P. Autoimmune hepatitis.  J Hepatol. 2000;  32 (Suppl. 1) 181-197
  Google Scholar
• 4 Lohse A W, Gerken G, Mohr H. et al . Relation between autoimmune liver diseases and viral hepatitis: Clinical and serological characteristics in 859 patients.  Z Gastroenterol. 1995;  33 527-533
  Google Scholar
• 5 International autoimmune hepatitis group report: Review of criteria for diagnosis of autoimmune hepatitis.  J Hepatol. 1999;  31 929-938
  Google Scholar
• 6 Ludwig J. Members of the Working Party of the World Congresses of Gastroenterology. Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions in the liver: Summary of recommendations developed by an international working party, supported by the World Congress of Gastroenterology, Los Angeles, 1994.  Am J Gastroenterol. 1994;  89 177-181
  Google Scholar
• 7 Desmet V J, Gerber M, Hoofnagle J H, Manns M, Scheuer P J. Classification of chronic hepatitis: Diagnosis, grading and staging.  Hepatology. 1994;  19 1513-1520
  Google Scholar
• 8 International W orking Party. Terminology of chronic hepatitis.  Am J Gastroenterol. 1995;  90 181-189
  Google Scholar
• 9 Meyer z um Büschenfelde KH, Lohse A W. Autoimmune hepatitis.  N Engl J Med. 1995;  333 1004-1005
  Google Scholar
• 10 Copenhagen S tudy Group for Liver Diseases. Effect of prednisolone on the survival of patients with cirrhosis of the liver.  Lancet. 1969;  1 119-121
  Google Scholar
• 11 Cook G C, Mulligan R, Sherlock S. Controlled prospective trial of corticosteroid therapy in chronic active hepatitis.  Q J Med. 1971;  40 159-185
  Google Scholar
• 12 Soloway R D, Summerskill W HJ, Baggenstoss A H. et al . Clinical, biochemical, and histological remission of severe chronic active liver disease: A controlled study of treatments and early prognosis.  Gastroenterology. 1972;  63 820-833
  Google Scholar
• 13 Murray-Lyon I M, Stern R B, Williams R. Controlled trial of prednisolone and azathioprine in active chronic hepatitis.  Lancet. 1973;  1 735-737
  Google Scholar
• 14 Maddrey W C, Combes B. Therapeutic concepts for the management of idiopathic autoimmune chronic active hepatitis.  Semin Liver Dis. 1991;  11 248-255
  Google Scholar
• 15 Czaja A J. Treatment of autoimmune hepatitis. Krawitt EL, Wiesner RH, Nishioka M Autoimmune hepatitis. 2nd ed Amsterdam; Elsevier Science BV 1998: 499-515
  Google Scholar
• 16 Johnson P J, McFarlane I G, Williams R. Azathioprine for long-term maintenance of remission in autoimmune hepatitis.  N Engl J Med. 1995;  333 958-963
  Google Scholar
• 17 Kirk A P, Jain S, Pocock S, Thomas H C, Sherlock S. Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis.  Gut. 1980;  21 78-83
  Google Scholar
• 18 Pratt D S, Flavin D P, Kaplan M M. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine.  Gastroenterology. 1996;  110 271-274
  Google Scholar
• 19 Hyams J S, Ballow M, Leichtner A M. Cyclosporine treatment of autoimmune chronic active hepatitis.  Gastroenterology. 1987;  93 890-893
  Google Scholar
• 20 Sherman K E, Narkewicz M, Pinto P C. Cyclosporine in the management of corticosteroid-resistant type I autoimmune chronic active hepatitis.  J Hepatol. 1994;  21 1040-1047
  Google Scholar
• 21 Van Thiel D H, Wright H, Carroll P. et al . Tacrolismus: A potential new treatment for autoimmune chronic active hepatitis: Results of an open-label preliminary trial.  Am J Gastroenterol. 1995;  90 771-776
  Google Scholar
• 22 Kanzler S, Gerken G, Dienes H P, Meyer z um Buschenfelde KH, Lohse A W. Cyclophosphamide as alternative immunosuppressive therapy for autoimmune hepatitis: Report of three cases.  Z Gastroenterol. 1997;  35 571-578
  Google Scholar
• 23 Czaja A J, Ammon H V, Summerskill W HJ. Clinical features and prognosis of severe chronic active liver disease (CALD) after corticosteroid-induced remission.  Gastroenterology. 1980;  78 518-523
  Google Scholar
• 24 Czaja A J, Beaver S J, Shiels M T. Sustained remission after corticosteroid therapy of severe hepatitis B surface antigen-negative chronic active hepatitis.  Gastroenterology. 1987;  92 215-219
  Google Scholar
• 25 Hegarty J E, Nouri-Aria K T, Portmann B, Eddleston A L, Williams R. Relapse following treatment withdrawal in patients with autoimmune chronic active hepatitis.  Hepatology. 1983;  3 685-689
  Google Scholar
• 26 Czaja A J, Ludwig J, Baggenstoss A H, Wolf A. Corticosteroid-treated chronic active hepatitis in remission: Uncertain prognosis of chronic persistent hepatitis.  N Engl J Med. 1981;  304 5-9
  Google Scholar
• 27 Davis G L, Czaja A J, Ludwig J. Development and prognosis of histologic cirrhosis in corticosteroid-treated HBsAg-negative chronic active hepatitis.  Gastroenterology. 1984;  87 122--1227
  Google Scholar
• 28 Roberts S K, Therneau T M, Czaja A J. Prognosis of histological cirrhosis in type 1 autoimmune hepatitis.  Gastroenterology. 1996;  110 848-857
  Google Scholar
• 29 Schvarcz R, Glaumann H, Weiland O. Survival and histological resolution of fibrosis in patients with autoimmune chronic active hepatitis.  J Hepatol. 1993;  18 15-23
  Google Scholar
• 30 Manns M, Gerken G, Kyriatsoulis A, Staritz M, Meyer z um Buschenfelde KH. Characterisation of a new soubgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen.  Lancet. 1987;  1 292-294
  Google Scholar
• 31 Wies I, Brunner S, Henninger. et al . Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis.  Lancet. 2000;  355 1510-1515
  Google Scholar
• 32 Kanzler S, Weidemann C, Gerken G. et al . Clinical significance of autoantibodies to soluble liver antigen in autoimmune hepatitis.  J Hepatol. 1999;  31 635-640
  Google Scholar
• 33 Summerskill W HJ, Korman M G, Ammon H V, Baggenstoss A H. Prednisone for chronic active liver disease: Dose titration, standard dose, and combination with azathioprine compared.  Gut. 1975;  16 876-883
  Google Scholar
• 34 Czaja A J. Autoimmune hepatitis: Evolving concepts and treatment strategies.  Dig Dis Sci. 1995;  40 435-456
  Google Scholar
• 35 Berg P A, Stechemesser E, Strienz J. Hypergammaglobulinämische chronisch aktive Hepatitis mit Nachweis von leber-pankreas-spezifischen komplementbindenden Autoantikörpern.  Verh Dtsch Ges Inn Med. 1981;  87 921-927
  Google Scholar
• 36 Gregorio G V, Portmann B, Reid F. et al . Autoimmune hepatitis in childhood: A 20-year experience.  Hepatology. 1997;  25 541-547
  Google Scholar
• 37 Kanzler S, Gerken G, Löhr H. et al . Duration of immunosuppressive therapy in autoimmune hepatitis (AIH).  J Hepatol. 2001;  34 354-355
  Google Scholar
• 38 Kinlen L J. Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment.  Am J Med. 1985;  78 44-49
  Google Scholar
• 39 Wang K K, Czaja A J, Beaver S J, Go V L. Extrahepatic malignancy following long-term immunosuppressive therapy of severe hepatitis B surface antigen-negative chronic active hepatitis.  Hepatology. 1989;  10 39-43
  Google Scholar
• 40 Johnson P J, McFarlane I G, Williams R. Azathioprine for long-term maintenance of remission in autoimmune hepatitis.  N Engl J Med. 1995;  333 958-963
  Google Scholar
• 41 Ewe K, Press A G, Singe C C. et al . Azathioprine combined with prednisolone or monotherapy witn prednisolone in active Crohn’s disease.  Gastroenterology. 1993;  105 367-372
  Google Scholar
• 42 Connell W R, Kamm M A, Dickson M. et al . Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease.  Lancet. 1994;  343 1249-1252
  Google Scholar
• 43 Omagari K, Kinoshita H, Kato Y. et al . Clinical features of 89 patients with autoimmune hepatitis in Nagasaki Prefecture, Japan.  J Gastroenterol. 1999;  34 221-226
  Google Scholar

Address for correspondence

Ansgar W. Lohse, MD

I. Department of Medicine
Johannes Gutenberg University

55101 MainzGermany

Email: lohse@mail.uni-mainz.de