AZATHIOPRINE FOR LONG-TERM MAINTENANCE OF REMISSION IN AUTOIMMUNE HEPATITIS

Background. In most patients with autoimmune hepatitis, remission can be maintained with prednisolone, usually in combination with azathiopr ine, but the majority of patients have a relapse when treatment is sto pped and therefore require long-term therapy. Because prolonged cortic osteroid therapy may have serious toxic effects, in 1984 we undertook a controlled trial of maintenance therapy with azathioprine alone. Non e of the 25 patients in that trial had relapses during the followup pe riod of one year. We have now followed these 25 patients for 10 years and have treated an additional 47 patients in a similar manner. Method s. 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 prednisol one per day and 1 mg of azathioprine per kilogram of body weight per d ay. The dose of azathioprine was increased to 2 mg per kilogram per da y, and the prednisolone was gradually withdrawn.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. Re sults. Sixty patients (83 percent) remained in remission while receivi ng 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 min imal disease, and 3 showed moderate disease (2 after one year of thera py and 1 after eight years). After the prednisolone had been withdrawn , 26 patients lost their cushingoid facies, and 32 patients lost weigh t (median loss, 6.4 kg; range, 1.5 to 22.3). The most common adverse e ffect was arthralgia (in 38 patients). With the higher dose of azathio prine, four patients had myelosuppression, defined as a decrease in th e leukocyte and platelet counts to less than 4000 and 150,000 per cubi c millimeter, respectively. Two of these patients (both with pancytope nia) relapsed when the azathioprine was withdrawn; in the other two, r emission was maintained with the resumption of prednisolone. Lymphopen ia developed in 32 of 56 patients treated with 2 mg of azathioprine pe r kilogram per day for more than two years. During follow-up, nine pat ients died: one of liver failure and eight of causes not directly rela ted to their liver disease. Conclusions. Many patients with autoimmune hepatitis who have been in complete remission for at least one year w ith prednisolone and azathioprine can remain in remission with a highe r dose of azathioprine alone.