[DRUG-INDUCED LIVER INJURY AND PYRAZINAMIDE USE].

Kekkaku : [Tuberculosis] Pub Date : 2015-03-01
Nobuyuki Horita, Naoki Miyazawa
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Abstract

Background: In the 1950s, high doses (40-70 mg/kg/day) of pyrazinamide were reported to cause drug-induced liver injury (DILI). It remains unclear whether adding pyrazinamide (Z) at the currently accepted low dose (20-25 mg/kg/day) to a regimen of isoniazid (H), rifampicin (R), and ethambutol (E) increases the risk of DILI.

Method: We reviewed adult patients admitted for smear-positive tuberculosis who were treated with a daily HRE or HRZE regimen. A Cox model was used to analyze the impact of pyrazinamide on the occurrence of DILI.

Results: We reviewed 195 patients (123 men [63%], 72 women [37%], average age 65 ± 19 years, 65 HRE patients [33%], 130 HRZE patients [67%]). The incidence of DILI in the first two months was 15% (29/195). The HRZE regimen was not associated with DILI (hazard ratio 0.55, P = 0.263).

Conclusion: Addition of low-dose (20-25 mg/kg/day) pyrazinamide to the HRE regimen does not appeared to be associated with increased DILI incidence during the first two months of treatment.

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[药物性肝损伤和吡嗪酰胺的使用]。
背景:在20世纪50年代,高剂量(40- 70mg /kg/天)吡嗪酰胺被报道可引起药物性肝损伤(DILI)。目前尚不清楚在异烟肼(H)、利福平(R)和乙胺丁醇(E)的治疗方案中以目前接受的低剂量(20- 25mg /kg/天)添加吡嗪酰胺(Z)是否会增加DILI的风险。方法:我们回顾了接受每日HRE或HRZE方案治疗的痰阳性结核病成年患者。采用Cox模型分析吡嗪酰胺对DILI发生的影响。结果:195例患者(男性123例[63%],女性72例[37%],平均年龄65±19岁,HRE 65例[33%],HRZE 130例[67%])。DILI在前两个月的发生率为15%(29/195)。HRZE方案与DILI无关(风险比0.55,P = 0.263)。结论:在HRE方案中添加低剂量(20- 25mg /kg/天)吡嗪酰胺似乎与治疗前两个月DILI发生率增加无关。
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