Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: A placebo-controlled clinical trial

Abstract

N-acetylcysteine (NAC) was found to improve transplantation-free survival in only those adults with non-acetaminophen (non-APAP) acute liver failure (ALF) and grade 1–2 hepatic encephalopathy (HE). Because non-APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non-APAP PALF. Children from birth through age 17 years with non-APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo-controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1-year survival. Secondary outcomes included liver transplantation-free survival, liver transplantation (LTx), length of ICU and hospital stays, organ system failure and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1-year survival did not differ significantly (p=0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1-year LTx-free survival was significantly lower (p=0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0–1 (NAC 25%; placebo 60%; p=0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE. Conclusion NAC did not improve 1-year survival in non-APAP PALF. 1-year LTx-free survival was significantly lower with NAC, particularly among those < 2 years old. These results do not support broad use of NAC in non-APAP PALF and emphasizes the importance of conducting controlled pediatric drug trials, regardless of results in adults.

Drug idiosyncrasy due to pirfenidone presenting as acute liver failure: Case report and mini‐review of the literature

“…N‐acetyl cysteine has been shown to improve transplant‐free survival in adults with DILI‐ALF 22. However, the results are contradictory in the pediatric population23 and equivocal in a prospective cohort study 24. LT is the only definitive treatment for those with poor prognosis 8.…”

Acute Liver Failure : Management Update

“…23 More recently, with improvements in management of critically ill children, coupled with a more lenient definition of pediatric acute liver failure, outcomes have improved. 24,25 However, it should be noted that all current studies of outcomes are affected by decisions about liver transplantation, because LT interrupts the natural course of PALF.…”

Idiosyncratic drug‐induced liver injury: A short review

“…For those with an etiology of DILI within the NAC trial,31 transplant‐free survival was 58% for those who received NAC versus 27% for those who did not receive NAC. However, the use of NAC in children with non‐APAP ALF demonstrated a lower rate of survival at 1 year; therefore, NAC is not recommended for children with severe iDILI leading to ALF 32. To date, the FDA has not approved NAC for the treatment of non‐APAP ALF.…”