Evaluation of the Association of N-Acetylcysteine and Mortality in Non-Acetaminophen-Induced Acute Liver Failure

Purpose Non-acetaminophen-induced acute liver failure (NAI-ALF) is associated with high mortality, with limited treatment options beyond supportive care and liver transplantation. While intravenous (IV) N-acetylcysteine (NAC) is the standard of care in acetaminophen-induced ALF, its benefit in NAI-ALF remains uncertain. Therefore, the purpose of this study is to evaluate the effect of IV NAC on in-hospital mortality. Methods We conducted a retrospective cohort study that included adult patients with NAI-ALF. Inverse probability of treatment weighting (IPTW) based on baseline demographics, severity of ALF, comorbidity burden, and etiology of ALF was conducted to balance the two groups. The primary outcome was all-cause in-hospital mortality at 21 days. Secondary outcomes included time to INR normalization, time to liver function test (LFT) normalization, and hospital length of stay. Results A total of 200 patients were included in the study, with 85 patients in the NAC group and 115 in the non-NAC group. After IPTW, groups were balanced with standardized mean differences of <0.1 for all covariates. IV NAC was associated with lower in-hospital mortality at 21 days (48.9% vs 62.1%, P < .01), with an odds ratio of 0.59 (95% CI 0.39 - 0.88). No difference was observed in time to INR normalization [HR 1.49 (95% CI 0.87 - 2.56, P = .15)], time to LFT normalization [HR 1.12 (95% CI 0.72 - 1.74, P = .61)], and length of hospital stay (11.9 vs 15.1 days, P = .84). Conclusion For patients with NAI-ALF, IV NAC administration was associated with a reduction in in-hospital mortality at 21 days. These findings suggest NAC could play a role in the management of patients with NAI-ALF. Larger prospective studies are needed to further clarify the role of NAC in this population.