Chughlay Mohamed Farouk, Kramer Nicole, Werfalli Mahmoud, Spearman Wendy, Engel Mark Emmanuel, Cohen Karen
Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa.
Clinical Research Centre, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa.
Syst Rev. 2015 Jun 12;4:84. doi: 10.1186/s13643-015-0075-6.
Drug-induced liver injury (DILI) refers to acute or chronic liver injury that may occur as a consequence of using drugs and herbal or dietary supplements. Specific therapies for DILI are limited. There is considerable evidence for efficacy and safety of N-acetylcysteine (NAC) in management of paracetamol-induced liver injury. More recently, research has explored the use of NAC in non-paracetamol drug-induced liver injury. It is important to summarise the evidence of NAC for non-paracetamol DILI to determine if NAC may be considered a therapeutic option in this condition.
METHODS/DESIGN: We will conduct a systematic review of the benefit and harm of NAC in non-paracetamol drug-induced liver injury. Primary and secondary outcomes of interest are pre-specified. Primary outcomes include all-cause mortality, mortality due to DILI, time to normalisation of liver biochemistry (e.g. return of alanine transaminase to <100 U/l and/or international normalized ratio (INR) <1.5) and adverse events. Secondary outcomes include transplantation rate, time to transplantation, transplant-free survival and duration of hospitalisation. We will include randomized controlled trials (RCTs) and prospective cohort studies. RCTs will contribute to the evaluation of safety and efficacy of NAC, whereas, the cohort studies will contribute exclusively to the evaluation of safety. We will search several bibliographic databases (including PubMed, Scopus, CINAHL, CENTRAL), grey literature sources, conference proceedings and ongoing trials. Following data extraction and assessment of the risk of bias, we will conduct a meta-analysis if feasible, as well as subgroup analyses. We will assess and explore clinical and statistical heterogeneity.
The aim of this review is to provide evidence on the effectiveness and safety of NAC in non-paracetamol DILI. We anticipate that the results could aid health care practitioners, researchers and policymakers in the decision-making regarding the use of NAC in patients with non-paracetamol DILI.
PROSPERO CRD42014008771.
药物性肝损伤（DILI）是指因使用药物、草药或膳食补充剂而可能发生的急性或慢性肝损伤。DILI的特异性治疗方法有限。有大量证据表明N-乙酰半胱氨酸（NAC）在对乙酰氨基酚所致肝损伤的治疗中具有有效性和安全性。最近，研究探索了NAC在非对乙酰氨基酚药物性肝损伤中的应用。总结NAC用于非对乙酰氨基酚DILI的证据，以确定在这种情况下NAC是否可被视为一种治疗选择，这一点很重要。
方法/设计：我们将对NAC在非对乙酰氨基酚药物性肝损伤中的益处和危害进行系统评价。预先设定感兴趣的主要和次要结局。主要结局包括全因死亡率、DILI所致死亡率、肝生化指标恢复正常的时间（如丙氨酸转氨酶恢复至<100 U/L和/或国际标准化比值（INR）<1.5）以及不良事件。次要结局包括移植率、移植时间、无移植生存率和住院时间。我们将纳入随机对照试验（RCT）和前瞻性队列研究。RCT将有助于评估NAC的安全性和有效性，而队列研究将仅有助于评估安全性。我们将检索多个文献数据库（包括PubMed、Scopus、CINAHL、CENTRAL）、灰色文献来源、会议论文集和正在进行的试验。在进行数据提取和偏倚风险评估后，我们将在可行的情况下进行荟萃分析以及亚组分析。我们将评估和探讨临床和统计学异质性。
本评价的目的是提供NAC在非对乙酰氨基酚DILI中的有效性和安全性的证据。我们预计该结果可帮助医疗保健从业者、研究人员和政策制定者在针对非对乙酰氨基酚DILI患者使用NAC的决策中提供参考。
PROSPERO CRD42014008771
