抗结核药物性肝损伤的静脉内 N-乙酰半胱氨酸治疗的随机对照试验。

A Randomized Controlled Trial of Intravenous N-Acetylcysteine in the Management of Anti-tuberculosis Drug-Induced Liver Injury.

机构信息

Department of Medicine, University of Cape Town, Cape Town, South Africa.

Department of Medicine, New Somerset Hospital, Cape Town, South Africa.

出版信息

Clin Infect Dis. 2021 Nov 2;73(9):e3377-e3383. doi: 10.1093/cid/ciaa1255.

DOI:10.1093/cid/ciaa1255

PMID:32845997

Abstract

BACKGROUND

Liver injury is a common complication of anti-tuberculosis therapy. N-acetylcysteine (NAC) used in patients with paracetamol toxicity with limited evidence of benefit in liver injury due to other causes.

METHODS

We conducted a randomized, double-blind, placebo-controlled trial to assess the efficacy of intravenous NAC in hospitalized adult patients with anti-tuberculosis drug-induced liver injury (AT-DILI). The primary endpoint was time for serum alanine aminotransferase (ALT) to fall below 100 U/L. Secondary endpoints included length of hospital stay, in-hospital mortality, and adverse events.

RESULTS

Fifty-three participants were randomized to NAC and 49 to placebo. Mean age was 38 (SD±10) years, 58 (57%) were female, 89 (87%) were HIV positive. Median (IQR) serum ALT and bilirubin at presentation were 462 (266-790) U/L and 56 (25-100) μmol/L, respectively. Median time to ALT <100 U/L was 7.5 (6-11) days in the NAC arm and 8 (5-13) days in the placebo arm. Median time to hospital discharge was shorter in the NAC arm (9 [6-15] days) than in the placebo arm (18 [10-25] days) (HR, 1.73; 95% CI, 1.13-2.65). Mortality was 14% overall and did not differ by study arm. The study infusion was stopped early due to an adverse reaction in 5 participants receiving NAC (nausea and vomiting [3], anaphylaxis [1], pain at drip site [1]).

CONCLUSIONS

NAC did not shorten time to ALT <100 U/L in participants with AT-DILI, but significantly reduced length of hospital stay. NAC should be considered in management of AT-DILI.

CLINICAL TRIALS REGISTRATION

South African National Clinical Trials Registry (SANCTR: DOH-27-0414-4719).

摘要

背景

肝损伤是抗结核治疗的常见并发症。N-乙酰半胱氨酸（NAC）用于治疗对乙酰氨基酚中毒，但其在其他原因导致的肝损伤中的疗效证据有限。

方法

我们进行了一项随机、双盲、安慰剂对照试验，以评估静脉内 NAC 对住院成人抗结核药物性肝损伤（AT-DILI）患者的疗效。主要终点是血清丙氨酸氨基转移酶（ALT）降至 100 U/L 以下的时间。次要终点包括住院时间、住院死亡率和不良事件。

结果

53 名参与者被随机分配到 NAC 组，49 名参与者被分配到安慰剂组。平均年龄为 38（SD±10）岁，58（57%）为女性，89（87%）为 HIV 阳性。入院时血清 ALT 和胆红素的中位数（IQR）分别为 462（266-790）U/L 和 56（25-100）μmol/L。NAC 组 ALT<100 U/L 的中位时间为 7.5（6-11）天，安慰剂组为 8（5-13）天。NAC 组的中位住院时间较短（9 [6-15]天），而安慰剂组为 18（10-25]天）（HR，1.73；95%CI，1.13-2.65）。总体死亡率为 14%，与研究组无关。由于 5 名接受 NAC 治疗的参与者发生不良反应（恶心和呕吐[3]，过敏反应[1]，滴注部位疼痛[1]），研究输注提前停止。