title: N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review.
abstract: N-acetylcysteine (NAC) may be useful in the management of non-paracetamol drug-induced liver injury (DILI). Our objective was to review systematically evidence for the use of NAC as a therapeutic option for non-paracetamol DILI.
  
  
  
  We searched for randomized controlled trials (RCTs) and prospective cohort studies. We searched several bibliographic databases, grey literature sources, conference proceedings and ongoing trials. Our pre-specified primary outcomes were all cause and DILI related mortality, time to normalization of liver biochemistry and adverse events. Secondary outcomes were proportion receiving liver transplant, time to transplantation, transplant-free survival and hospitalization duration.
  
  
  
  We identified one RCT of NAC vs. placebo in patients with non-paracetamol acute liver failure. There was no difference in the primary outcomes of overall survival at 3 weeks between NAC [70%, 95% confidence interval (CI) = 60%, 81%, n = 81] and placebo (66%, 95% CI = 56%, 77%, n = 92). NAC significantly improved the secondary outcomes of transplant-free survival compared with placebo: 40% NAC (95% CI = 28%, 51%) vs. 27% placebo (95% CI = 18%, 37%). A subgroup analysis according to aetiology found improved transplant-free survival in patients with non-paracetamol DILI, NAC (58%, n = 19) vs. placebo (27%, n = 26), odds ratio (OR) 0.27 (95% CI = 0.076, 0.942). Overall survival was similar, NAC (79%) vs. placebo (65%);, OR 0.50 (95% CI = 0.13, 1.98).
  
  
  
  Current available evidence is limited and does not allow for any firm conclusions to be made regarding the role of NAC in non-paracetamol DILI. We therefore highlight the need for further research in this area.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town.
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.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kramer
authors.affiliation: Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town.
authors.forename: C Wendy
authors.initials: CW
authors.lastname: Spearman
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.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Werfalli
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town.
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*; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans
chemical_list: D016166:Free Radical Scavengers; D000111:Acetylcysteine
keywords: N-acetylcysteine; drug-induced; hepatitis; liver failure; non-acetaminophen; non-paracetamol