巯嘌呤解救柳氮磺胺吡啶诱导的炎症性肠病肝损伤。

Mercaptopurine rescue after azathioprine-induced liver injury in inflammatory bowel disease.

机构信息

Department of Gastroenterology, Hospital Universitario de Fuenlabrada, Madrid, Spain.

出版信息

Aliment Pharmacol Ther. 2010 Jan;31(1):120-4. doi: 10.1111/j.1365-2036.2009.04132.x.

DOI:10.1111/j.1365-2036.2009.04132.x

PMID:19709096

Abstract

BACKGROUND

Azathioprine (AZA) liver toxicity arises in approximately 3% of inflammatory bowel disease patients and may result in treatment discontinuation.

AIM

To describe the tolerance to mercaptopurine (MP) in patients with previous AZA-related liver injury.

METHODS

Retrospective description of 31 patients (14 Crohn's, 17 ulcerative colitis), in which AZA therapy was interrupted because of liver injury, with MP started as alternative therapy.

RESULTS

Mean AZA dose was 2.2 +/- 0.4 mg x kg/day. Median (interquartile range) of AZA exposure when liver injury was detected was 2 months (1-5.2). The type of AZA-related injury was cytolitic in 32%, cholestatic in 39% and mixed in 29%. After a median of 2.5 months (0.7-5.2), the therapy was switched to MP at a mean dose of 1.3 +/- 0.2 mg x kg/day. Median of follow-up of MP therapy was 32 months (8-54). In 87.1% of patients (95%CI: 70-96%), MP was tolerated without further liver injury; of these, 77.4% tolerated full MP doses and 9.7% tolerated lower doses. In a further cohort of 12.9% of patients, (95%CI: 3-29%), liver injury reappeared (two cholestasis, two mixed), 1-3 months after the onset of MP exposure.

CONCLUSION

The administration of MP is a good alternative in patients with AZA-related liver injury, before thiopurines are definitely discarded.

摘要

背景

巯嘌呤（MP）在大约 3%的炎症性肠病患者中引起肝毒性，可能导致治疗中断。

目的

描述巯嘌呤（MP）在有既往 AZA 相关肝损伤的患者中的耐受性。

方法

回顾性描述了 31 例患者（14 例克罗恩病，17 例溃疡性结肠炎），由于肝损伤中断了 AZA 治疗，改用 MP 作为替代治疗。

结果

AZA 的平均剂量为 2.2 ± 0.4 mg/kg/天。肝损伤检测时 AZA 暴露的中位数（四分位距）为 2 个月（1-5.2）。AZA 相关损伤的类型为细胞溶解型占 32%，胆汁淤积型占 39%，混合型占 29%。在中位时间为 2.5 个月（0.7-5.2）后，将治疗方案切换至平均剂量为 1.3 ± 0.2 mg/kg/天的 MP。MP 治疗的中位随访时间为 32 个月（8-54）。在 87.1%的患者（95%可信区间：70-96%）中，MP 耐受且无进一步肝损伤；其中，77.4%的患者耐受全量 MP，9.7%的患者耐受低剂量 MP。在另外 12.9%的患者（95%可信区间：3-29%）中，在开始使用 MP 后 1-3 个月，再次出现肝损伤（2 例胆汁淤积，2 例混合型）。