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Critical Care  2009 

Prolonged N-acetylcysteine therapy in late acetaminophen poisoning associated with acute liver failure – a need to be more cautious?

DOI: 10.1186/cc7800

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The paper entitled 'Prolonged treatment with N-acetylcysteine delays liver recovery from acetaminophen hepatotoxicity' by Yang and colleagues [1], published in the previous issue of Critical Care, demonstrates that prolonged administration of N-acetylcysteine (NAC) at 100 mg/kg in acetaminophen (APAP)-induced liver failure in mice potentially limits hepatocellular regeneration. Activation of a transcription factor, nuclear factor-kappa-B (NF-κB), strongly linked to impairment of liver regeneration, is a putative mechanism for this. Furthermore, the paper postulates that high doses of NAC may interfere with normal metabolic processes of the liver, leading to impairment of its regenerative capacity [1].NAC has been used since the 1970s, and it effectively manages APAP poisoning by glutathione repletion if administered within 8 to 10 hours of ingestion of the overdose [2]. In later years, clinical use of NAC was extended to patients who present more than 10 hours after ingestion and to those with APAP-induced acute liver failure (ALF), and patients in such categories are routinely on NAC infusions for many days, even weeks [3,4]. The putative protective mechanisms of NAC in late-APAP poisoning and APAP-induced liver failure remain poorly characterised but include free-radical scavenging, hemodynamic, and cytokine effects [1,5,6]. Concern has been expressed relating to its extended use in late presenters with APAP poisoning and APAP-induced liver failure because of the possibility of changed kinetics of NAC in liver injury, reduced efficacy, and adverse hemodynamic changes (vasodilatation and increased cardiac index) [7]. This new study raises the issue of whether impairment of regeneration is also a clinical concern for extended NAC use.A key issue in liver recovery after any acute injury is tissue repair and regeneration. Such liver regeneration involves replication of mature parenchyma and non-parenchyma liver cells, which requires multiple cytokine and growth factor


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