Hepato-Gastroenterology and Tropical Medicine Department, Faculty of Medicine, Cairo University, 63 Abo Dawood El-Thahery St., Nasr City, Cairo, Egypt.
Anesthesiology and ICU Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Clin Drug Investig. 2017 May;37(5):473-482. doi: 10.1007/s40261-017-0505-4.
Previous studies and systematic reviews have not provided conclusive evidence on the effect of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). We aimed to study the value of intravenous NAC in reducing liver transplantation and mortality in NAI-ALF.
In a prospective, multicenter, observational study, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were enrolled. NAC infusion (in empirical dose) was given as 150 mg/kg in 100 ml dextrose 5% over half an hour, then 70 mg/kg in 500 ml dextrose 5% over 4 h, then 70 mg/kg in 500 ml dextrose 5% over 16 h. Thereafter continuous infusion was administered over 24 h of 150 mg/kg in 500 ml dextrose 5% until up to two consecutive normal international normalized ratios (INRs) were obtained. Our endpoints were recovery, transplantation, or death. The primary outcome of the study was to assess reduction in mortality or liver transplantation. The secondary outcome was the evaluation of other clinical outcomes (length of ICU and hospital stays, organ system failure, and hepatic encephalopathy).
The study included a total of 155 adults; the NAC group (n = 85) were given NAC between January 2011 to December 2013 and the control group (n = 70) were not given NAC and were included from files dating between 2010 and 2011. Both groups (before NAC) were comparable with regard to etiology, age, sex, smoking, presence of co-morbidities, encephalopathy, liver profile, and INR. The success rate (transplant-free survival) in the NAC group was 96.4%. While in the control group, 17 patients (23.3%) recovered and 53 (76.6%) did not recover, of these 37 (53.3%) had liver transplantation and 16 (23.3%) died (p < 0.01). The NAC group had significantly shorter hospital stays (p < 0.001), less encephalopathy (p = 0.02), and less bleeding (p < 0.01) than the control group. The control group reported a higher ICU admission (p = 0.01) rate and abnormal creatinine and electrolytes (p = 0.002, p < 0.01, respectively). Liver profile and INR (after NAC infusion) differed significantly between the two groups with regard to bilirubin (increased in controls, p = 0.02), AST and INR (decreased in NAC group, p < 0.001 for both), but the ALT decrease showed no statistical significance between the two groups.
When administered on admission, intravenous NAC caused a reduction in NAI-ALF mortality and need for transplantation. NAC decreased encephalopathy, hospital stay, ICU admission, and failure of other organs.
以前的研究和系统评价并没有提供关于 N-乙酰半胱氨酸（NAC）在非乙酰氨基酚诱导的急性肝衰竭（NAI-ALF）中作用的明确证据。我们旨在研究静脉内 NAC在降低 NAI-ALF 肝移植和死亡率方面的价值。
在一项前瞻性、多中心、观察性研究中，纳入了没有临床或历史证据表明乙酰氨基酚过量的急性肝衰竭患者。给予 NAC 输注（经验剂量），在 30 分钟内将 150mg/kg 的 NAC 加入 100ml 5%葡萄糖中，然后在 4 小时内将 70mg/kg 的 NAC 加入 500ml 5%葡萄糖中，然后在 16 小时内将 70mg/kg 的 NAC 加入 500ml 5%葡萄糖中。之后，以 150mg/kg 的剂量在 500ml 5%葡萄糖中连续输注 24 小时，直到连续两次获得正常的国际标准化比值（INR）。我们的终点是恢复、移植或死亡。研究的主要结局是评估死亡率或肝移植的降低。次要结局是评估其他临床结局（ICU 和住院时间、器官系统衰竭和肝性脑病）。
该研究共纳入 155 名成年人；NAC 组（n=85）在 2011 年 1 月至 2013 年 12 月期间接受 NAC 治疗，对照组（n=70）未接受 NAC 治疗，纳入时间为 2010 年至 2011 年的病历。两组（NAC 治疗前）在病因、年龄、性别、吸烟、合并症、肝性脑病、肝功能、INR 等方面具有可比性。NAC 组的成功率（无肝移植存活率）为 96.4%。而在对照组中，17 名患者（23.3%）恢复，53 名患者（76.6%）未恢复，其中 37 名患者（53.3%）进行了肝移植，16 名患者（23.3%）死亡（p<0.01）。与对照组相比，NAC 组的住院时间明显缩短（p<0.001），肝性脑病发生率较低（p=0.02），出血较少（p<0.01）。对照组 ICU 入院率（p=0.01）和肌酐及电解质异常（p=0.002，p<0.01）较高。两组患者在胆红素方面有显著差异（对照组升高，p=0.02），AST 和 INR 方面有显著降低（NAC 组降低，均为 p<0.001），但两组 ALT 降低无统计学差异。
在入院时给予静脉内 NAC 可降低 NAI-ALF 的死亡率和移植需求。NAC 降低了肝性脑病、住院时间、ICU 入院率和其他器官衰竭的发生率。
