Azathioprine for long-term maintenance of remission in autoimmune hepatitis

N Engl J Med. 1995 Oct 12;333(15):958-63. doi: 10.1056/NEJM199510123331502.


Background: In most patients with autoimmune hepatitis, remission can be maintained with prednisolone, usually in combination with azathioprine, but the majority of patients have a relapse when treatment is stopped and therefore require long-term therapy. Because prolonged corticosteroid therapy may have serious toxic effects, in 1984 we undertook a controlled trial of maintenance therapy with azathioprine alone. None of the 25 patients in that trial had relapses during the follow-up period of one year. We have now followed these 25 patients for 10 years and have treated an additional 47 patients in a similar manner.

Methods: The 72 patients (median age, 47 years; range, 14 to 71) had been in complete remission for at least one year with 5 to 15 mg of prednisolone per day and 1 mg of azathioprine per kilogram per day. The dose of azathioprine was increased to 2 mg per kilogram per day, and the prednisolone was gradually withdrawn. Remission was defined as the absence of symptoms suggestive of a relapse and serum globulin and aspartate aminotransferase concentrations within the normal range, with or without a liver biopsy showing only minimal inflammation.

Results: Sixty patients (83 percent) remained in remission while receiving azathioprine alone for a median of 67 months (range, 12 to 128). Of 48 follow-up liver biopsies in 42 patients, 45 showed inactive or minimal disease, and 3 showed moderate disease (2 after one year of therapy and 1 after eight years). After the prednisolone had been withdrawn, 26 patients lost their cushingoid facies, and 32 patients lost weight (median loss, 6.4 kg; range, 1.5 to 22.3). The most common adverse effect was arthralgia (in 38 patients). With the higher dose of azathioprine, four patients had myelosuppression, defined as a decrease in the leukocyte and platelet counts to less than 4000 and 150,000 per cubic millimeter, respectively. Two of these patients (both with pancytopenia) relapsed when the azathioprine was withdrawn; in the other two, remission was maintained with the resumption of prednisolone. Lymphopenia developed in 32 of 56 patients treated with 2 mg of azathioprine per kilogram per day for more than two years. During follow-up, nine patients died: one of liver failure and eight of causes not directly related to their liver disease.

Conclusions: Many patients with autoimmune hepatitis who have been in complete remission for at least one year with prednisolone and azathioprine can remain in remission with a higher dose of azathioprine alone.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arthralgia / chemically induced
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Azathioprine / administration & dosage
  • Azathioprine / therapeutic use*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Hepatitis / drug therapy*
  • Hepatitis / immunology
  • Humans
  • Leukocyte Count / drug effects
  • Male
  • Middle Aged
  • Platelet Count / drug effects
  • Prednisolone / adverse effects
  • Prednisolone / therapeutic use
  • Recurrence
  • Substance Withdrawal Syndrome
  • Treatment Outcome


  • Prednisolone
  • Azathioprine