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 3weeks 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.