Safety and efficacy of N-acetylcysteine in children with non-acetaminophen-induced acute liver failure

Abstract

Acute liver failure (ALF) carries a high mortality in children. N-acetylcysteine (NAC), an antioxidant agent that replenishes mitochondrial and cytosolic glutathione stores, has been used in the treatment of late acetaminophen-induced ALF and non-acetaminophen-induced ALF. In our unit, NAC was introduced as additional treatment for non-acetaminophen-induced ALF in 1995. The aim of this study was to evaluate the safety and efficacy of NAC in children with ALF not caused by acetaminophen poisoning. A retrospective review of medical records of 170 children presenting with nonacetaminopheninduced ALF between 1989 and 2004 was undertaken. ALF was defined as either international normalized ratio of prothrombin time (INR) Ͼ 2 and abnormal liver function or INR Ͼ1.5 with encephalopathy and abnormal liver function. Children were divided into the following groups: Group 1 (1989)(1990)(1991)(1992)(1993)(1994), standard care (n ϭ 59; 34 [58%] male; median age 2.03 yr, range 0.003-15.8 yr); and Group 2 (1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004), standard care and NAC administration (n ϭ 111; 57 [51%] male; median age 3.51 yr, range 0.005-17.4 yr). NAC was administered as a continuous infusion (100 mg/kg/24 hours) until INR Ͻ 1.4, death, or liver transplantation (LT). The median duration of NAC administration in Group 2 was 5 (range, 1-77) days. Complications were noted in 8 (10.8%) children: rash in 3, arrhythmia in 3, and dizziness and peripheral edema in 1. One child had an allergic reaction (bronchospasm) and NAC was stopped. A total of 41 (71%) children in Group 1 vs. 85 (77%) in Group 2 required admission to intensive care, P ϭ not significant (ns). The length of intensive care stay was 6 (range, 1-58) days in Group 1 vs. 5 (range, 1-68) days in Group 2, P ϭ ns and length of hospital stay was 25 (range, 1-264) days vs. 19 (range, 1-201) days, P ϭ 0.05. The 10-yr actuarial survival was 50% in Group 1 compared to 75% in Group 2, P ϭ 0.009. Survival with native liver occurred in 13 (22%) in Group 1 vs. 48 (43%) in Group 2, P ϭ 0.005; 15 (25%) in Group 1 died without transplant vs. 21 (19%) in Group 2, P ϭ ns; and LT was performed in 32 (54%) vs. 42 (38%), P ϭ ns. Death after transplantation occurred in 15 (39%) in Group 1 vs. 8 (16%) in Group 2, P ϭ 0.02. In conclusion, NAC is safe in non-acetaminophen-induced ALF. In this retrospective study NAC was associated with a shorter length of hospital stay, higher incidence of native liver recovery without transplantation, and better survival after transplantation. Liver Transpl 14: [25][26][27][28][29][30] 2008 See Editorial on Page 7Acute liver failure (ALF) in children is a rare but often fatal condition without liver transplantation (LT). [1][2][3] Multiorgan dysfunction in ALF is believed to derive from oxidative stress due to reactive oxygen species and reactive nitrogen species 4 and from immunological injury mediated by cytokines. 5-8 N-acetylcysteine (NAC) is a thiol-containing agent that scavenges free oxygen radicals and replenishes cellular mitochon...

N-Acetyl cysteine in non-acetaminophen pediatric acute liver failure: Recent evidence !

“…They recommended routine use of NAC in the dose of 100 mg/kg/day in all cases of ALF irrespective of the etiology. This was based on a retrospective single site review involving 170 children done by Kortsalioudaki, et al [2]. In this study NAC was associated with a shorter length of hospital stay, higher incidence of native liver recovery without transplantation, and better survival after transplantation.…”

“…N-acetyl cysteine (NAC) replenishes mitochondrial and cytosolic glutathione stores and is the treatment of choice for acute acetaminophen toxicity. Studies in the past have shown some role of NAC in non-acetaminophen ALF [2,3].…”

“…recommended the use of N-acetylcysteine in the treatment of children with non-acetaminophen pediatric acute liver failure [1]. Intravenous N-acetyleysteine (NAC) was incorporated into the general management of acute liver failure following a small uncontrolled study suggesting improved cardiovascular hemodynamics and oxygen transport in liver failure in adults [2]. In pediatric population, NAC became popular after a retrospective In a recently published consensus statement on management of acute liver failure, the authors have…”

Is there a “NAC” to treating acute liver failure in children?

“…In this issue of Liver Transplantation, Kortsalioudaki et al 7 describe the presentation, management, and outcome of a large series of patients diagnosed with non-APAP-induced ALF who have been treated with NAC. Several prior studies have reported the use of NAC for non-APAP-induced ALF; however, the number of patients reported has been low and none of the studies have been adequately controlled.…”

“…In the current study, Kortsalioudaki et al 7 performed a retrospective analysis of 170 children diagnosed with non-APAP-induced ALF at King's College Hospital between 1989 and 2004. A total of 59 patients (Group 1) treated from 1989 to 1994, an era prior to the routine use of NAC for non-APAP-induced ALF at this institution, were compared to 111 children (Group 2) diagnosed between 1995 and 2004.…”