Efficacy and safety of acetylcysteine in "non-acetaminophen'' acute liver failure: A meta-analysis of prospective clinical trials
Efficacy and safety of acetylcysteine in "non-acetaminophen'' acute liver failure: A meta-analysis of prospective clinical trials
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DOI：
10.1016/j.clinre.2015.01.003
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发表时间：
2015-10-01
影响因子：
2.7
通讯作者：
Quan, Qizhen
中科院分区：
文献类型：
--
作者：
Hu, Jinhua;Zhang, Qizhi;Quan, Qizhen
背景：急性肝功能衰竭（ALF）是一种罕见的，但高度致命的条件，没有肝移植（LT）。N-乙酰半胱氨酸（NAC）是一种谷胱甘肽前体，可使对乙酰氨基酚的活性代谢产物解毒并减少肝脏谷胱甘肽储存，是预防对乙酰氨基酚引起的ALF的高效药物。然而，NAC在非对乙酰氨基酚诱导的ALF（NAI-ALF）（包括酒精中毒、肝炎病毒感染或药物和毒素相关的肝毒性）中的治疗用途仍无定论。本文的目的是采用荟萃分析方法对近期关于NAC治疗非醋氨酚中毒所致ALF患者的安全性和有效性的前瞻性临床试验进行分析。通过检索Pubmed，确定了比较NAC和对照治疗NAI-ALF的疗效和安全性的前瞻性临床试验（2000-2014）和EMBASE（2000-2014），使用检索词乙酰半胱氨酸或NAC和NAI-ALF。主要结局是总生存期。次要结果包括无肝移植存活率、移植后存活率、ICU时间和住院时间，以及与昏迷等级的关系。结果：共纳入4篇临床试验进行Meta分析。共纳入331例接受NAC（口服或静脉注射）治疗的患者和285例对照组患者进行荟萃分析。NAC组和对照组的总生存期无统计学差异[236/331（71%）vs 191/285（67%）; 95%CI 1.16（0.81-1.67）; P = 0.42]。然而，NAC组与对照组在自体肝存活率方面存在显著差异[112/273（41%）vs 68/226（30%; 95%CI 1.61（1.11-2.34）; P = 0.01]和移植后存活率[78/91（85.7%）vs 50/70（71.4%）; 95%CI 2.44（1.11-5.37）; P = 0.03]。NAC的副作用包括恶心、呕吐、腹泻或便秘。罕见的情况下，它可能会导致皮疹，发烧，头痛，嗜睡，低血压，并在囊性纤维化患者血清转氨酶水平升高。结论：NAC对NAI-ALF是安全的。它可以延长患者自体肝不移植的生存期和移植后的生存期，但不能提高总生存期。(C)2015年由Elsevier Masson SAS出版。
Background: Acute liver failure (ALF) is a rare but highly mortal condition without liver transplantation (LT). N-acetylcysteine (NAC), a glutathione precursor that detoxifies the reactive metabolite of acetaminophen and replenishes hepatic glutathione stores, is a highly effective drug for the prevention of ALF caused by acetaminophen. However, therapeutic use of NAC in non-acetaminophen-induced ALF (NAI-ALF) including alcohol intoxication, hepatitis virus infection, or drug and toxin-related hepatotoxicity is still inconclusive. The aim of this article is using meta-analysis method to analyze recent prospective clinical trials for the safety and efficacy of NAC in patients with ALF not caused by acetaminophen poisoning.Methods: Prospective clinical trials comparing efficacy and safety between NAC and control in the treatment of NAI-ALF were identified by searching Pubmed (2000-2014) and EMBASE (2000-2014) using the search terms acetylcysteine or NAC and NAI-ALF. The primary outcome was overall survival. Secondary outcomes included liver transplantation-free survival, post transplantation survival, length of ICU and hospital stays, and the relationship with coma grade. The safety profiles were also analyzed.Results: Four clinical trials were selected for meta-analysis. A total of 331 patients receiving treatment with NAC (oral or intravenously) and 285 patients in control group were included for meta-analysis. No statistical difference was identified between NAC group and control group for overall survival [236/331 (71%) vs 191/285 (67%); 95% CI 1.16 (0.81-1.67); P = 0.42]. However, there were significant differences between NAC group and control group regarding the survival with native liver [112/273 (41%) vs 68/226 (30%); 95% CI 1.61 (1.11-2.34); P = 0.01] and posttransplantation survival [78/91 (85.7%) vs 50/70 (71.4%); 95% CI 2.44 (1.11-5.37); P = 0.03]. The identified side effects of NAC included nausea, vomiting, and diarrhea or constipation. Rarely, it could cause rashes, fever, headache, drowsiness, low blood pressure, and elevated serum transaminase levels in a patient with cystic fibrosis. At the dose used for acetaminophen toxicity, acetylcysteine does not have hepatotoxic effects.Conclusion: NAC is safe for NAI-ALF. It can prolong patients' survival with native liver without transplantation and survival after transplantation, but it cannot improve the overall survival. (C) 2015 Published by Elsevier Masson SAS.