Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
Clin Gastroenterol Hepatol. 2019 Sep;17(10):2068-2075.e2. doi: 10.1016/j.cgh.2018.12.035. Epub 2019 Jan 6.
BACKGROUND & AIMS: Patients with autoimmune hepatitis (AIH) commonly receive induction therapy with predniso(lo)ne followed by maintenance therapy with azathioprine. European Association for Study of the Liver clinical practice guidelines advise a predniso(lo)ne dose range of 0.50-1 mg/kg/day, which leaves room for practice variation. We performed a multicenter study to determine the efficacy of different dose ranges of predniso(lo)ne induction therapy in a large European cohort of patients with AIH.
We performed a retrospective cohort study using a comparative effectiveness design. We collected data from 451 adults with AIH who began treatment from 1978 through 2017 at 9 centers in 5 European countries. We assigned patients to a high-dose group (initial predniso(lo)ne dose ≥0.50 mg/kg/day; n = 281) or a low-dose group (<0.50 mg/kg/day; n = 170). Logistic regression was performed to determine difference in outcomes between the groups. The primary outcome was normal serum levels of transaminases at 6 months after initiation of therapy.
There was no significant difference in rates of normalization of transaminases between the high-dose predniso(lo)ne group and the low-dose group (70.5% vs 64.7%; P = .20). After multivariable logistic regression with correction for confounders, there was no difference in the likelihood of normalization of transaminases between the groups (odds ratio, 1.21; 95% CI, 0.78-1.87; P = .38). Patients given an initial high dose of predniso(lo)ne received more predniso(lo)ne over time than patients started on a lower dose (median doses over 6 months: 3780 mg vs 2573 mg) (P < .01).
In a retrospective study of patients with AIH in Europe, we found that the dose of predniso(lo)ne to induce remission in patients with AIH is less relevant than assumed. An initial predniso(lo)ne dose below 0.50 mg/kg/day substantially decreases unnecessary exposure to predniso(lo)ne in patients with AIH.
自身免疫性肝炎（AIH）患者通常接受泼尼松龙诱导治疗，随后用硫唑嘌呤维持治疗。欧洲肝脏研究协会临床实践指南建议泼尼松龙剂量范围为 0.50-1mg/kg/日，这为实践中的差异留出了空间。我们进行了一项多中心研究，以确定在欧洲的一个大型 AIH 患者队列中，不同剂量范围的泼尼松龙诱导治疗的疗效。
我们采用比较效果设计进行了回顾性队列研究。我们从 1978 年至 2017 年期间在欧洲 5 个国家的 9 个中心接受治疗的 451 名成人 AIH 患者中收集数据。我们将患者分配到高剂量组（初始泼尼松龙剂量≥0.50mg/kg/日；n=281）或低剂量组（<0.50mg/kg/日；n=170）。使用逻辑回归确定两组之间结局的差异。主要结局是治疗开始后 6 个月时血清转氨酶正常水平。
高剂量泼尼松龙组与低剂量组的转氨酶正常率无显著差异（70.5%比 64.7%；P=.20）。在进行了多变量逻辑回归校正混杂因素后，两组之间转氨酶正常的可能性没有差异（比值比，1.21；95%CI，0.78-1.87；P=.38）。给予初始高剂量泼尼松龙的患者在治疗期间接受的泼尼松龙剂量多于初始剂量较低的患者（中位数剂量在 6 个月内：3780mg 比 2573mg）（P<0.01）。
在欧洲 AIH 患者的回顾性研究中，我们发现诱导 AIH 缓解的泼尼松龙剂量并不像预期的那么重要。初始泼尼松龙剂量低于 0.50mg/kg/日可显著减少 AIH 患者不必要的泼尼松龙暴露。
