Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver Failure
Intravenous N-Acetylcysteine Improves Transplant-Free Survival in Early Stage Non-Acetaminophen Acute Liver Failure
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DOI：
10.1053/j.gastro.2009.06.006
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发表时间：
2009-09-01
期刊：
影响因子：
29.4
通讯作者：
Robuck, Patricia R.
中科院分区：
文献类型：
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作者：
Lee, William M.;Hynan, Linda S.;Robuck, Patricia R.
背景与目的：N-乙酰半胱氨酸（NAC）是对乙酰氨基酚中毒的解毒剂，可能对非对乙酰氨基酚相关急性肝衰竭患者有益。方法：在一项前瞻性双盲试验中，没有对乙酰氨基酚过量临床或历史证据的急性肝衰竭患者按部位和昏迷级别分层，并随机分配到接受72小时NAC或安慰剂（葡萄糖）输注的组中。主要结局是3周时的总生存率。次要结果包括无移植存活率和移植率。结果：共173例患者接受NAC（n = 81）或安慰剂（n = 92）。NAC组患者3周总生存率为70%，安慰剂组为66%（单侧P = 0.283）。NAC患者的无移植生存率（40%）显著优于安慰剂组（27%;单侧P = 0.043）。无移植生存期的益处仅限于114名接受NAC的昏迷I-II级患者（52%，而安慰剂组为30%;单侧P = 0.010）; 59名昏迷III-IV级患者的无移植生存率在接受NAC的患者中为9%，在接受安慰剂的患者中为22%（单侧P = 0.912）。NAC组的移植率较低，但组间无显著差异（32% vs 45%; P = 0.093）。静脉注射NA通常耐受良好; NAC组中仅恶心和呕吐发生率显著更高（14% vs 4%; P = 0.031）。结论：静脉注射NAC可提高早期非醋氨酚相关急性肝衰竭患者的无移植存活率。晚期昏迷患者不能从NAC中获益，通常需要紧急肝移植。
BACKGROUND & AIMS: N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. METHODS: In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. RESULTS: A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NA generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). CONCLUSIONS: Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.