Role of N-acetylcysteine in non-acetaminophen-related acute liver failure: an updated meta-analysis and systematic review

Abstract

Background The American Association for the Study of Liver Diseases recommends that N-acetylcysteine (NAC) may be beneficial in non-acetaminophen-related drug-induced liver injury. A subsequent review and analysis reported the current evidence to be inconclusive. Herein, we present an updated review and meta-analysis. Methods We evaluated prospective, retrospective and randomized controlled trials that compared outcomes in patients of all ages with acute liver failure (defined as abnormal liver enzymes along with elevated international normalized ratio >1.5, with or without hepatic encephalopathy) receiving NAC with the outcomes in a control group. The primary outcome was to compare the overall survival in the 2 groups. Secondary outcomes included difference in length of hospital stay, transplant-free survival, and post-transplant survival. Results Seven studies (N=883) that met the inclusion criteria were included in this analysis. The mean age of patients in the NAC group was 21.22 years compared with 23.62 years in the control group. The odds of overall survival were significantly higher in the NAC group than in controls (odds ratio [OR] 1.77, 95% confidence interval [CI] 1.3-2.41). Post-transplant survival (OR 2.44, 95%CI 1.11-5.37) and transplant-free survival were also better in the NAC group than in the control group (OR 2.85, 95%CI 2.11-3.85). Patients in the control group had statistically significant odds of a longer inpatient stay (mean difference 7.79, 95%CI 6.93-8.66). Conclusion In patients with non-acetaminophen-related acute liver failure, NAC significantly improves overall survival, post-transplant survival and transplant-free survival while decreasing the overall length of hospital stay.

N-Acetylcysteine (NAC): Impacts on Human Health

“…The administration of intravenous NAC in patients with acute liver failure not induced by paracetamol shortly after admission reduces mortality and the need for liver transplantation, in addition to reduced encephalopathy, hospitalization, admission to the intensive care unit and failure of other organs [ 157 ]. Corroborating these data, a recent meta-analysis also concluded that NAC improves survival, transplant-free survival, post-transplant survival and length of hospital stay for patients with acute liver failure unrelated to paracetamol [ 158 ].…”

Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury

“…Pharmacological interventions such as supplementation of antioxidants to reduce the oxidative stress have been explored to minimize the risk of liver damage 8 – 10 . The FDA approved drug N-acetylcysteine (NAC) is an antioxidant and glutathione inducer indicated for the treatment of fulminant liver failure due to paracetamol overdose 11 . NAC has also been utilized for ameliorating hepatocyte damage in IRI experimental models, while more clinic outcome data is required before the routine use of NAC 12 , 13 .…”

Dosage of N-Acetyl Cysteine in Acute Liver Failure Not Related to Acetaminophen

“…2,6 In a recent metaanalysis of 7 studies, the use of NAC was associated with improvement in OS, TFS and PTS in patients with NA-ALF. 7 There was significant reduction in duration of hospital stay. In this meta-analysis, most common etiology of ALF was acute viral hepatitis.…”

“…11 A systemic review comparing oral and intravenous NAC showed similar level of hepatotoxicity in rats with acetaminophen overdose and route of dosing didn't make much difference. 7 One fears that oral NAC may have impaired absorption in, poor tolerance (due to nausea and vomiting), delayed gastric emptying and intestinal failure in setting of ALF. 11 A prospective study which included the sick patients with ALF failed to show any significant benefit (in terms of OS and duration of hospital stay) using NAC by oral route.…”

“…INASL has recommended the dosage used by most of the studies.. 5 , 12 , 13 The safety and tolerability of NAC is well established and minor adverse events reported include allergic reactions (Bronchospasm, rash), cardiac arrhythmias and peripheral edema. 7 A summary of these studies have been provided in Table-1. 1,3,5,12,13,14,15,16,17…”