We read with interest the current consensus statement on management of
acute liver failure in infants and children [1]. Pediatric acute liver
failure (ALF) is a devastating disease in which previously healthy
children rapidly lose hepatic function due to a variety of causes and
become critically ill within days. Management is largely supportive and
only few conditions are amenable to directed therapy, such as acute
acetaminophen toxicity. 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].
The writing committee stated that there is increasing
evidence for use of NAC infusion in non-acetaminophen causes of ALF [1].
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.
However, a recent well designed placebo controlled
trial conducted by the Pediatric Acute Liver Failure Study Group does
not support the broad use of NAC in non-acetaminophen Pediatric ALF [4].
This multi-centre trial included 184 children under the age of 18 years.
The study group found that NAC did not improve 1-year survival in
children with non-acetaminophen ALF. One-year liver transplant free
survival was significantly lower in the NAC-treated group, especially
among children less than 2 years of age with HE grade 0-1. This study
emphasized the importance of conducting prospective pediatric drug
trials.
With the availability of new evidence in recent
literature, indiscriminate use of NAC in all cases of pediatric ALF is
not justified.
1. Bhatia V, Bavdekar A, Yachha SK for the Pediatric
Gastroenterology Chapter of Indian Academy of Pediatrics. Management of
Acute Liver Failure in Infants and Children: Consensus Statement of the
Pediatric Gastroenterology Chapter, Indian Academy of Pediatrics. Indian
Pediatr. 2013;50:477-82.
2. Kortsalioudaki C, Taylor RM, Cheeseman P, Bansal
S, Mieli-Vergani G, Dhawan A. Safety and efficacy of N-acetylcysteine in
children with non-acetaminophen-induced acute liver failure. Liver
Transpl. 2008;14:25-30.
3. Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz
RT, Larson AM, et al. Intravenous N-acetylcysteine improves
transplant-free survival in early stage non-acetaminophen acute liver
failure. Gastroenterology. 2009;137:856-64.
4. Squires RH, Dhawan A, Alonso E, Narkewicz MR,
Shneider BL, Rodriguez-Baez N, et al. Intravenous N-acetylcysteine
in pediatric patients with nonacetaminophen acute liver failure: A
placebo-controlled clinical trial. Hepatology. 2013;57:1542-9.