Efficacy and safety of N-acetylcysteine for the treatment of non-acetaminophen-induced acute liver failure: an updated systematic review and meta-analysis

Introduction
N-acetylcysteine (NAC) is the treatment of choice for acetaminophen-induced liver injury. However, recent years have witnessed growing interest in its role in the treatment of acute liver failure (ALF) due to other aetiologies. This study aims to determine both its safety and efficacy by pooling data from multiple studies.

Material and methods
A search was conducted for all controlled randomized/non-randomized studies that measured the efficacy and safety of NAC in adult patients with non-acetaminophen-induced acute liver failure (NAI-ALF). Transplant-free survival (TFS) was considered the primary endpoint, while secondary endpoints such as length of hospital stay, and incidence of adverse events during treatment, were included in our analysis. Data were pooled via a random-effects model, I2 was used as a measure of heterogeneity, and publication bias was assessed via a funnel plot.

Results
A total of 3 studies [2 randomized controlled trials (RCTs) and 1 non-randomized cohort] were pooled in this meta-analysis. TFS was significantly higher in patients given NAC, when compared to the placebo/control (PBO) group (RR = 1.54, CI = 1.19-1.98, p = 0.01, I2 = 0.0%). No secondary endpoint was observed to have improved significantly in patients prescribed NAC: length of hospital stay (SMD = –0.405, CI = –1.44-0.63, p = 0.445, I2 = 91.1%), renal failure (RR = 1.01, CI = 0.65-1.57, p = 0.967, I2 = 21.3%), infections (RR = 1.18, CI = 0.91-1.52, p = 0.208, I2 = 2.3%), pulmonary failure (RR = 1.19, CI = 0.57-2.49, p = 0.649, I2 = 84.6%). Minimal side effects were reported in around 10-14% of the patients prescribed NAC.

Conclusions
NAC was shown to significantly improve TFS in adult patients with NAI-ALF, while no significant benefit was observed concerning the secondary endpoints of length of hospital stay and incidence of adverse effects.