title: N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review protocol.
abstract: BACKGROUND
  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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  PROSPERO CRD42014008771.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa. CHGMOH001@myuct.ac.za.
authors.forename: Mohamed Farouk
authors.initials: MF
authors.lastname: Chughlay
authors.affiliation: Clinical Research Centre, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa. Nicky.kramer@uct.ac.za.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kramer
authors.affiliation: Division of Endocrinology and Diabetes, Chronic Disease Initiative in Africa (CDIA) Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa. Werfy@live.co.za.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Werfalli
authors.affiliation: Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa. Wendy.spearman@uct.ac.za.
authors.forename: Wendy
authors.initials: W
authors.lastname: Spearman
authors.affiliation: Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa. mark.engel@uct.ac.za.
authors.forename: Mark Emmanuel
authors.initials: ME
authors.lastname: Engel
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa. Karen.cohen@uct.ac.za.
authors.forename: Karen
authors.initials: K
authors.lastname: Cohen
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D002985:Clinical Protocols; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D012107:Research Design; D000078202:Systematic Reviews as Topic
chemical_list: D016166:Free Radical Scavengers; D000111:Acetylcysteine