Zizzo Andréanne N, Valentino Pamela L, Shah Prakesh S, Kamath Binita M
*The Hospital for Sick Children †University of Toronto, Toronto, Ontario, Canada ‡Yale University School of Medicine, New Haven, CT §Mount Sinai Hospital, Toronto ||London Health Sciences Centre, Western University, London, Ontario, Canada.
J Pediatr Gastroenterol Nutr. 2017 Jul;65(1):6-15. doi: 10.1097/MPG.0000000000001530.
Ten percent to 20% of children with autoimmune hepatitis (AIH) require second-line therapy to achieve remission. Although current guidelines exist on first-line management, evidence for second-line therapy in treatment-refractory patients is lacking. Our aim was to perform a systematic review and meta-analysis of the efficacy and safety of second-line treatments used in this population.
Electronic and manual searches were used to identify potential studies for inclusion. Studies were selected based on reported response rates to second-line therapies in children who failed response to prednisone and azathioprine. Data extraction and risk of bias assessment were performed independently by 2 reviewers. Meta-analysis using weighted estimate of response rates at 6 months was performed for each treatment option. Heterogeneity was assessed.
Fifteen studies of 76 pediatric patients with AIH were included in the review. Overall response rates at 6 months were estimated as 36% for mycophenolate mofetil (MMF) (N = 34, 95% confidence interval [CI] (16-57)), and 50% for tacrolimus (N = 4, 95% CI (0-100%)) and 83% for cyclosporine (N = 15, 95% CI (66%-100%)). Adverse effects were most frequent with cyclosporine (64% experiencing at least 1 adverse effect) followed by tacrolimus (54%) and MMF (48%). Pooled estimates of adverse events were 78% for cyclosporine (95% CI (54%-100%)), 42% for tacrolimus (95% CI (0%-85%)) and 45% for MMF (95% CI (25%-68%)). Sensitivity analyses were not performed due to small sample size.
Cyclosporine had the highest response rate at 6 months in children with standard-treatment-refractory AIH; however, it also had the highest rate of adverse events. MMF was the second most efficacious option with a low adverse effect rate.
10%至20%的自身免疫性肝炎（AIH）患儿需要二线治疗才能实现缓解。尽管目前存在关于一线治疗管理的指南，但对于治疗难治性患者的二线治疗证据不足。我们的目的是对该人群中使用的二线治疗的疗效和安全性进行系统评价和荟萃分析。
采用电子检索和手工检索来确定可能纳入的研究。根据对泼尼松和硫唑嘌呤治疗无反应的儿童中二线治疗的报告缓解率来选择研究。由两名审阅者独立进行数据提取和偏倚风险评估。对每个治疗方案进行使用6个月缓解率加权估计的荟萃分析。评估异质性。
该评价纳入了15项针对76例AIH儿科患者的研究。6个月时，霉酚酸酯（MMF）（N = 34，95%置信区间[CI]（16 - 57））的总体缓解率估计为36%，他克莫司（N = 4，95% CI（0 - 100%））为50%，环孢素（N = 15，95% CI（66% - 100%））为83%。不良反应最常见于环孢素（64%至少经历1次不良反应），其次是他克莫司（54%）和MMF（48%）。不良事件的合并估计值为环孢素78%（95% CI（54% - 100%）），他克莫司42%（95% CI（0% - 85%）），MMF 45%（95% CI（25% - 68%））。由于样本量小，未进行敏感性分析。
在标准治疗难治性AIH患儿中，环孢素在6个月时的缓解率最高；然而，其不良反应发生率也最高。MMF是第二有效的选择，不良反应率较低。
