N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review

作者：Chughlay Mohamed Farouk; Kramer Nicole; Spearman C Wendy; Werfalli Mahmoud; Cohen Karen^*

来源：British Journal of Clinical Pharmacology, 2016, 81(6): 1021-1029.

DOI：10.1111/bcp.12880

• drug-induced
• hepatitis
• liver failure
• N-acetylcysteine
• non-acetaminophen
• non-paracetamol

AIMS
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.
METHODS
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.
RESULTS
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).
CONCLUSION
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.

• 出版日期2016-6