Licata Anna, Minissale Maria Giovanna, Stankevičiūtė Simona, Sanabria-Cabrera Judith, Lucena Maria Isabel, Andrade Raul J, Almasio Piero Luigi
Medicina Interna ed Epatologia, Dipartimento di Promozione della Salute, Materno-infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro," PROMISE, Università degli Studi di Palermo, Palermo, Italy.
UCICEC IBIMA, Plataforma SCReN (Spanish Clinical Research Network), Malaga, Spain.
Front Pharmacol. 2022 Aug 10;13:828565. doi: 10.3389/fphar.2022.828565. eCollection 2022.
N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment. Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs). In total, 34 studies of NAC usage in APAP-related DILI cases with 19,580 patients were identified, of which 2,376 patients developed hepatotoxicities. The mortality rate across different studies ranged from 0 to 52%. Large variability of NAC regimens was found, i.e., intravenous (I.V.) (100-150 mg/kg) and oral (70-140 mg/kg), and length of treatment varied-12, 24, or 48 h for I.V. regimen and 72 h for oral administration. The timing of initiation of NAC treatment showed different results in terms of occurrence of hepatotoxicity and mortality; if started within 8 h and no more than 24 h from APAP overdose, either intravenously or orally, NAC administration was efficacious in terms of mortality. The most frequent AEs reported were anaphylactic reactions, followed by cutaneous AEs for the IV route and intestinal AEs for the oral one. NAC improves hepatotoxicity and reduces mortality. Timing of treatment, ranging from 8 to 24 h from APAP overdose, regardless of the regimen or route of administration, is important to prevent or minimize liver damage, particularly in children and in elderly and obese patients.
N-乙酰半胱氨酸（NAC）被用作对乙酰氨基酚（APAP）过量中毒的解毒剂，以预防和减轻药物性肝损伤（DILI）。我们的目标是系统回顾NAC作为APAP过量中毒及APAP相关DILI治疗选择的证据，以确定最佳治疗方案和开始治疗的时机。检索了文献数据库（PubMed、科学网、Embase和MEDLINE），查找回顾性和前瞻性队列研究、病例系列和临床试验。预先设定的主要结局为DILI相关死亡率、肝毒性和不良事件（AE）。共识别出34项关于NAC用于APAP相关DILI病例的研究，涉及19580例患者，其中2376例患者出现肝毒性。不同研究中的死亡率在0%至52%之间。发现NAC治疗方案差异很大，即静脉注射（I.V.）（100 - 150mg/kg）和口服（70 - 140mg/kg），治疗时长也不同——静脉注射方案为12、24或48小时，口服给药为72小时。NAC治疗开始的时机在肝毒性和死亡率方面显示出不同结果；如果在APAP过量中毒后8小时内且不超过24小时开始，无论静脉注射还是口服，NAC给药在死亡率方面都是有效的。报告的最常见不良事件是过敏反应，其次是静脉注射途径的皮肤不良事件和口服途径的肠道不良事件。NAC可改善肝毒性并降低死亡率。从APAP过量中毒后8至24小时开始治疗，无论治疗方案或给药途径如何，对于预防或最小化肝损伤都很重要，尤其是在儿童、老年人和肥胖患者中。
