N-acetylcysteine for non-paracetamol-induced acute liver failure in children: A systematic review and meta-analysis

AIM: Non-surgical treatment of acute liver failure (ALF) is primarily supportive and depends on the underlying cause. While N-acetylcysteine (NAC) is proven effective in paracetamol-induced ALF, its potential benefits in non-paracetamol ALF for paediatric patients remain unclear. This systematic review aimed to evaluate the efficacy of NAC in paediatric patients with non-paracetamol-induced ALF.

METHODS: PubMed and Embase were searched for studies published before 20 August 2025. The review was registered on PROSPERO (CRD420251146345). Eligible studies included paediatric patients receiving NAC for non-paracetamol-induced ALF. Primary outcomes were overall survival and transplant-free survival.

RESULTS: Statistical analyses were performed with Review Manager version 7.2.0 with a random-effect model, and heterogeneity was assessed with I2. Risk of bias 2 and risk of bias in non-randomized studies of interventions were used for bias assessment. The meta-analysis included 310 patients receiving NAC and 242 controls. Overall survival was 77.7% in the NAC group and 73.5% in controls (OR 1.34, 95% CI: 0.90-1.99, p = .15). Transplant-free survival was 60.1% for NAC and 61.6% for controls (OR 0.81, 95% CI 0.26-2.46, p = .71).

CONCLUSIONS: Current evidence indicates that NAC does not significantly impact overall survival and transplant-free survival in paediatric patients with non-paracetamol-induced ALF. Given the limited availability of randomized controlled trials, future research should preferably include such study designs, although ethical challenges may limit feasibility. Systematic collection of clinical data remains essential to better assess potential therapeutic effects. Current literature does not support the use of NAC in non-paracetamol-induced ALF in children.