Department of Gastroenterology & Clinical Nutrition, The Royal Children's Hospital.
Department of Immunology, University of Melbourne, Melbourne, Australia.
J Pediatr Gastroenterol Nutr. 2018 Dec;67(6):695-700. doi: 10.1097/MPG.0000000000002146.
Azathioprine (AZA) is the mainstay of maintenance therapy in pediatric autoimmune hepatitis (AIH). The use of thiopurines metabolites to individualize therapy and avoid toxicity has not, however, been clearly defined.
Retrospective analysis of children ≤18 years diagnosed with AIH between January 2001 and 2016. Standard definitions were used for treatment response and disease flare. Thiopurine metabolite levels were correlated with the corresponding liver function test.
A total of 56 children (32 girls) were diagnosed with AIH at a median age of 11 years (interquartile range [IQR] 9). No difference in 6-thioguanine-nucleotide (6-TG) levels (271[IQR 251] pmol/8 × 10 red blood cell vs 224 [IQR 147] pmol/8 × 10 red blood cell, P = 0.06) was observed in children in remission when compared with those who were not in remission. No correlation was observed between the 6-TG and alanine aminotransferase levels (r = -0.179, P = 0.109) or between 6-methyl-mercaptopurine (6-MMP) and alanine aminotransferase levels (r = 0.139, P = 0.213). The 6-MMP/6-TG ratio was significantly lower in patients who were in remission (2[7] vs 5 (10), P = 0.04). Using a quartile analysis, we found that having a ratio of <4 was significantly associated with being in remission with OR 2.50 (95% confidence interval 1.02-6.10), P = 0.047. Use of allopurinol with low-dose AZA in 6 children with preferential 6-MMP production brought about remission in 5/6 (83.3%).
Thiopurine metabolite levels should be measured in patients with AIH who have experienced a loss of remission. A 6-MMP/6-TG ratio of <4 with the addition of allopurinol could be considered in these patients.
硫唑嘌呤（AZA）是儿童自身免疫性肝炎（AIH）维持治疗的主要药物。然而，尚未明确使用硫嘌呤代谢物来实现个体化治疗并避免毒性。
回顾性分析 2001 年 1 月至 2016 年期间诊断为 AIH 的≤18 岁儿童。使用标准定义来评估治疗反应和疾病发作。将硫嘌呤代谢物水平与相应的肝功能测试相关联。
共诊断出 56 名（32 名女性）AIH 儿童，中位年龄为 11 岁（四分位距 [IQR] 9）。与未缓解的儿童相比，缓解期儿童的 6-硫鸟嘌呤核苷酸（6-TG）水平（271[IQR 251] pmol/8×10 红细胞与 224 [IQR 147] pmol/8×10 红细胞，P=0.06）无差异。6-TG 与丙氨酸氨基转移酶水平之间无相关性（r= -0.179，P=0.109），6-甲基巯基嘌呤（6-MMP）与丙氨酸氨基转移酶水平之间也无相关性（r= -0.139，P=0.213）。缓解期患者的 6-MMP/6-TG 比值显著降低（2[7]比 5（10），P=0.04）。通过四分位数分析，我们发现比值<4 与缓解显著相关，OR 2.50（95%置信区间 1.02-6.10），P=0.047。6 名优先产生 6-MMP 的患儿使用小剂量 AZA 和别嘌呤醇治疗，其中 5/6（83.3%）缓解。
在经历缓解期丧失的 AIH 患者中，应测量硫嘌呤代谢物水平。对于这些患者，可考虑添加别嘌呤醇以获得比值<4 的 6-MMP/6-TG。
