Title : Efficacy and safety of n – acetylcysteine in non – acetaminophen – induced pediatric acute liver failure: A meta – analysis
Background: Pediatric acute liver failure (ALF) is a devastating disease in which previously healthy children rapidly lose hepatic function due to a variety of causes and become critically ill within days. Management is largely supportive and only few conditions are amenable to directed therapy, such as acute acetaminophen toxicity. One such directed therapy which is very controversial to this day due to contrasting findings in past studies is the use of N-acetylcysteine (NAC) in non-acetaminophen pediatric ALF (NA-PALF).
Objective: To evaluate the efficacy and safety of NAC in pediatric patients with ALF not caused by acetaminophen poisoning by determining the hospital mortality and transplant-free survival of pediatric patients with NA-PALF given NAC as well as the adverse effects during its use.
Methodology: This is a meta-analysis done to evaluate the role of NAC in NA-PALF. We searched electronic databases for studies published until 2021 and used RevMan software to analyze the data extracted from selected studies. Outcome estimation was done using Odds Ratio (OR) with 95% confidence interval (CI). The heterogeneity in various studies was determined using the I2 test.
Results: Seven studies were included in the qualitative analysis while four studies were analyzed quantitatively. The major finding of our study was a 65% reduction in hospital mortality (OR: 0.35, 95% CI, 0.20 to 0.61) in patients receiving NAC compared to standard of care, which was statistically significant. There was also increased transplant-free survival (OR: 1.11, 95% CI, 0.20 to 6.18) and the proportion of adverse events under the NAC group (OR: 1.62, 95% CI, 0.82 to 3.22) was just slightly higher than standard care, but were not considered significant. Majority of the adverse events were minor and self-limited. Heterogeneity existed in the transplant-free survival but was not present in the hospital mortality and adverse events.
Conclusion: We found that NAC can reduce the hospital mortality of pediatric patients with NA-ALF. It may be safe to use whenever we encounter children with NA-ALF. However, since the findings of prolonged patients’ survival with native liver without transplantation were not statistically significant, we can conclude that the use of NAC was comparable to standard of care. Results must be interpreted with caution as the results obtained had high heterogeneity and different study designs.
Recommendation: Additional large prospective pediatric studies are needed to determine the optimal dose, route and duration of NAC therapy, predictors of response, and the physiologic basis for these improved outcomes.
Keywords: N-acetylcysteine, NAC, pediatric acute liver failure, non-acetaminophen-induced liver failure