Johnson P J, McFarlane I G, Williams R
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
N Engl J Med. 1995 Oct 12;333(15):958-63. doi: 10.1056/NEJM199510123331502.
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.
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 The dose of azathioprine was increased to 2 mg per kilogram per day, and the prednisolone was gradually withdrawn.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.
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 After the prednisolone had been withdrawn, 26 patients lost their cushingoid facies, and 32 patients lost weight (median loss, 6.4 kg; range, 1.5 to 22.3).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 Two of these patients (both with pancytopenia) relapsed when the azathioprine was withdrawn; in the other two, remission was maintained with the resumption of prednisolone.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.
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.
在大多数自身免疫性肝炎患者中，泼尼松龙通常联合硫唑嘌呤可维持病情缓解，但大多数患者在停药后会复发，因此需要长期治疗。由于长期使用皮质类固醇疗法可能会产生严重的毒性作用，1984年我们进行了一项单独使用硫唑嘌呤维持治疗的对照试验。该试验中的25例患者在一年的随访期内均未复发。我们现在已对这25例患者进行了10年的随访，并以类似方式治疗了另外47例患者。
72例患者（年龄中位数47岁；范围14至71岁）曾使用每日5至15毫克泼尼松龙和每日每千克体重1毫克硫唑嘌呤完全缓解至少一年。硫唑嘌呤剂量增至每日每千克体重2毫克，泼尼松龙逐渐停用。缓解的定义为无提示复发的症状，血清球蛋白和天冬氨酸转氨酶浓度在正常范围内，无论肝活检是否仅显示轻微炎症。
60例患者（83%）单独接受硫唑嘌呤治疗期间病情持续缓解，中位数为67个月（范围12至128个月）。在42例患者的48次随访肝活检中，45次显示为静止或轻微病变，3次显示为中度病变（治疗一年后2次，治疗八年后1次）。停用泼尼松龙后，26例患者库欣面容消失，32例患者体重减轻（体重减轻中位数6.4千克；范围1.5至22.3千克）。最常见的不良反应是关节痛（38例患者）。使用较高剂量硫唑嘌呤时，4例患者出现骨髓抑制，定义为白细胞计数和血小板计数分别降至每立方毫米低于4000和150,000。其中2例患者（均为全血细胞减少）停用硫唑嘌呤后复发；另外2例患者通过重新使用泼尼松龙维持缓解。在56例接受每日每千克体重2毫克硫唑嘌呤治疗超过两年的患者中，32例出现淋巴细胞减少。随访期间，9例患者死亡：1例死于肝衰竭，8例死于与肝病无直接关系的原因。
许多使用泼尼松龙和硫唑嘌呤完全缓解至少一年的自身免疫性肝炎患者，单独使用较高剂量硫唑嘌呤可维持缓解。
