What is the rationale for using N-acetylcysteine (NAC) in the treatment of non-acetaminophen-related liver failure (NALF)?

Although  the evidence on the effectiveness of NAC in NALF has often been inconclusive, an 2021 meta-analysis and systematic review of the role of NAC in NALF concluded that NAC significantly improves overall survival, post-transplant survival and transplant-free survival while decreasing the overall length of hospital stay (1). 

This meta-analysis included 7 studies involving 883 patients with a mean age of 21 years in the NAC group. Significantly higher overall survival (O.R. 1.8), post-transplant survival (O.R. 2.4) and transplant-free survival (O.R. 2.9) were observed in the NAC group. 

Previously, a 2009 randomized-controlled study involving adults with NALF (including many due to drug toxicity, hepatitis B virus-HBV, and autoimmune causes) had found longer transplant-free survival—not overall survival—in the treatment group, especially among those with lower grade encephalopathy, or liver failure caused by drugs or HBV (2). 

Although it’s not clear how NAC might work in the setting of of NALF, possible effect on microcirculation or 02 delivery through interference with cytokines or other mechanisms have been suggested (2,3).  An interesting 2013 article reported lower serum levels of interleukin-17 among treated patients (3)!

Bonus Pearl: Did you know that acute liver failure affects 2000-3000 persons in the U.S. each year with a mortality as high as 30%? (3)

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  1. Walayat S, Shaoib H, Asghar M, et al. Role of N-acetylcysteine in non-acetominophen-related acute liver failure: an updated meta-analysis and systematic review. Ann Gastroenterol 2021;34, 1-6. http://www.annalsgastro.gr/files/journals/1/earlyview/2021/ev-01-2021-04-AG_5321-0571.pdf 
  2. Bass S, Zook N. Intravenous acetylcysteine for indications other than acetaminophen overdose. Am J Health-Syst Pharm 2013;70:1496-1501. https://www.ncbi.nlm.nih.gov/pubmed/23943180
  3. Stravitz RT, Sanyal AJ, Reisch J, et al. Effects of N-acetylcysteine on cytokines in non-acetaminophen acute liver failure: potential mechanism of improvement in transplant-free survival. Liver Int. 2013;33:1324-1331. https://utsouthwestern.pure.elsevier.com/en/publications/effects-of-n-acetylcysteine-on-cytokines-in-non-acetaminophen-acu

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!


What is the rationale for using N-acetylcysteine (NAC) in the treatment of non-acetaminophen-related liver failure (NALF)?

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