Monthly Archives: October 2013

Don’t be cavalier about tylenol– just a little too much can have dire effects including liver failure

I recently listened to an eye-opening podcast from This American Life which details that on average 150 people die each year from unintentional tylenol toxicity. Many others end up with organ failure often resulting in transplantation. You can read the transcript or listen to the podcast . Who among us hasn’t once taken a few more tylenol than recommended? I for one am guilty but never again after learning that just a small amount of acetaminophen over the recommended dosage can set off a cascade of health events.  As a medical librarian, I also did research on Pubmed ( the major database of medical literature) and here is a selected list of 21 recent articles on the topic of acetaminophen toxicity and liver failure.

Selected , recent  English language articles on liver failure and acetaminophen (tylenol)

1. Leonis MA, Alonso EM, Im K, Belle SH, Squires RH; Pediatric Acute Liver

Failure Study Group. Chronic acetaminophen exposure in pediatric acute liver

failure. Pediatrics. 2013 Mar;131(3):e740-6. doi: 10.1542/peds.2011-3035. Epub

2013 Feb 25. PubMed PMID: 23439908; PubMed Central PMCID: PMC3581836.

 

2, Court MH, Freytsis M, Wang X, Peter I, Guillemette C, Hazarika S, Duan SX,
Greenblatt DJ, Lee WM; Acute Liver Failure Study Group. The
UDP-glucuronosyltransferase (UGT) 1A polymorphism c.2042C>G (rs8330) is
associated with increased human liver acetaminophen glucuronidation, increased
UGT1A exon 5a/5b splice variant mRNA ratio, and decreased risk of unintentional
acetaminophen-induced acute liver failure. J Pharmacol Exp Ther. 2013
May;345(2):297-307. doi: 10.1124/jpet.112.202010. Epub 2013 Feb 13. PubMed PMID: 
23408116; PubMed Central PMCID: PMC3629801.

 

3. Gulmez SE, Larrey D, Pageaux GP, Lignot S, Lassalle R, Jové J, Gatta A,
McCormick PA, Metselaar HJ, Monteiro E, Thorburn D, Bernal W, Zouboulis-Vafiadis 
I, de Vries C, Perez-Gutthann S, Sturkenboom M, Bénichou J, Montastruc JL,
Horsmans Y, Salvo F, Hamoud F, Micon S, Droz-Perroteau C, Blin P, Moore N.
Transplantation for acute liver failure in patients exposed to NSAIDs or
paracetamol (acetaminophen): the multinational case-population SALT study. Drug
Saf. 2013 Feb;36(2):135-44. doi: 10.1007/s40264-012-0013-7. PubMed PMID:
23325533; PubMed Central PMCID: PMC3568201.

4. Craig DG, Zafar S, Reid TW, Martin KG, Davidson JS, Hayes PC, Simpson KJ. The
sequential organ failure assessment (SOFA) score is an effective triage marker
following staggered paracetamol (acetaminophen) overdose. Aliment Pharmacol Ther.
2012 Jun;35(12):1408-15. doi: 10.1111/j.1365-2036.2012.05102.x. Epub 2012 Apr 23.
PubMed PMID: 22524320.

 

5. Craig DG, Zafar S, Reid TW, Martin KG, Davidson JS, Hayes PC, Simpson KJ. The
sequential organ failure assessment (SOFA) score is an effective triage marker
following staggered paracetamol (acetaminophen) overdose. Aliment Pharmacol Ther.
2012 Jun;35(12):1408-15. doi: 10.1111/j.1365-2036.2012.05102.x. Epub 2012 Apr 23.
PubMed PMID: 22524320.

 

6. Craig DG, Reid TW, Wright EC, Martin KG, Davidson JS, Hayes PC, Simpson KJ.
The sequential organ failure assessment (SOFA) score is prognostically superior
to the model for end-stage liver disease (MELD) and MELD variants following
paracetamol (acetaminophen) overdose. Aliment Pharmacol Ther. 2012
Mar;35(6):705-13. doi: 10.1111/j.1365-2036.2012.04996.x. Epub 2012 Jan 20. PubMed
PMID: 22260637.

 

7. Audimoolam VK, Wendon J, Bernal W, Heaton N, O'Grady J, Auzinger G. Iron and 
acetaminophen a fatal combination? Transpl Int. 2011 Oct;24(10):e85-8. doi:
10.1111/j.1432-2277.2011.01322.x. Epub 2011 Aug 30. PubMed PMID: 21883506.

 

8. Sabaté M, Ibáñez L, Pérez E, Vidal X, Buti M, Xiol X, Mas A, Guarner C, Forné
M, Solà R, Castellote J, Rigau J, Laporte JR. Paracetamol in therapeutic dosages 
and acute liver injury: causality assessment in a prospective case series. BMC
Gastroenterol. 2011 Jul 15;11:80. doi: 10.1186/1471-230X-11-80. PubMed PMID:

21762481; PubMed Central PMCID: PMC3150324.

9. Sabaté M, Ibáñez L, Pérez E, Vidal X, Buti M, Xiol X, Mas A, Guarner C, Forné
M, Solà R, Castellote J, Rigau J, Laporte JR. Paracetamol in therapeutic dosages 
and acute liver injury: causality assessment in a prospective case series. BMC
Gastroenterol. 2011 Jul 15;11:80. doi: 10.1186/1471-230X-11-80. PubMed PMID:

21762481; PubMed Central PMCID: PMC3150324.

10, Ceelie I, James LP, Gijsen V, Mathot RA, Ito S, Tesselaar CD, Tibboel D,
Koren G, de Wildt SN. Acute liver failure after recommended doses of
acetaminophen in patients with myopathies. Crit Care Med. 2011 Apr;39(4):678-82. 
doi: 10.1097/CCM.0b013e318206cc8f. PubMed PMID: 21242792; PubMed Central PMCID:
PMC3209512.

 

11. Lavonas EJ, Reynolds KM, Dart RC. Therapeutic acetaminophen is not associated
with liver injury in children: a systematic review. Pediatrics. 2010
Dec;126(6):e1430-44. doi: 10.1542/peds.2009-3352. Epub 2010 Nov 22. Review.
PubMed PMID: 21098156.

12. Jepsen P, Schmidt LE, Larsen FS, Vilstrup H. Long-term prognosis for
transplant-free survivors of paracetamol-induced acute liver failure. Aliment
Pharmacol Ther. 2010 Oct;32(7):894-900. doi: 10.1111/j.1365-2036.2010.04419.x.
PubMed PMID: 20735774.
13. Karvellas CJ, Safinia N, Auzinger G, Heaton N, Muiesan P, O'Grady J, Wendon
J, Bernal W. Medical and psychiatric outcomes for patients transplanted for
acetaminophen-induced acute liver failure: a case-control study. Liver Int. 2010 
Jul;30(6):826-33. doi: 10.1111/j.1478-3231.2010.02243.x. Epub 2010 Apr 8. PubMed 
PMID: 20408947.

 

14. Mehrpour O, Shadnia S, Sanaei-Zadeh H. Late extensive intravenous
administration of N-acetylcysteine can reverse hepatic failure in acetaminophen
overdose. Hum Exp Toxicol. 2011 Jan;30(1):51-4. doi: 10.1177/0960327110366182.
Epub 2010 Mar 23. PubMed PMID: 20332167.

 

15. Khan LR, Oniscu GC, Powell JJ. Long-term outcome following liver
transplantation for paracetamol overdose. Transpl Int. 2010 May 1;23(5):524-9.
doi: 10.1111/j.1432-2277.2009.01007.x. Epub 2009 Nov 25. PubMed PMID: 20002359.

 

16. Cooper SC, Aldridge RC, Shah T, Webb K, Nightingale P, Paris S, Gunson BK,
Mutimer DJ, Neuberger JM. Outcomes of liver transplantation for paracetamol
(acetaminophen)-induced hepatic failure. Liver Transpl. 2009 Oct;15(10):1351-7.
doi: 10.1002/lt.21799. PubMed PMID: 19790165.

 

17. Simpson KJ, Bates CM, Henderson NC, Wigmore SJ, Garden OJ, Lee A, Pollok A, 
Masterton G, Hayes PC. The utilization of liver transplantation in the management
of acute liver failure: comparison between acetaminophen and non-acetaminophen
etiologies. Liver Transpl. 2009 Jun;15(6):600-9. doi: 10.1002/lt.21681. PubMed
PMID: 19479803.

18. 125: Gentili A, Latrofa ME, Giuntoli L, Melchionda F, Pession A, Lima M,
Baroncini S. Acute liver failure associated with a prolonged course of
acetaminophen at recommended dosages in paediatric age. Pediatr Med Chir. 2008
Nov-Dec;30(6):302-5. PubMed PMID: 19431953.

19. Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang
H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical
features, and outcomes from a prospective study of drug-induced liver injury in
the United States. Gastroenterology. 2008 Dec;135(6):1924-34, 1934.e1-4. doi:
10.1053/j.gastro.2008.09.011. Epub 2008 Sep 17. PubMed PMID: 18955056; PubMed
Central PMCID: PMC3654244.

 

20. Fontana RJ. Acute liver failure including acetaminophen overdose. Med Clin
North Am. 2008 Jul;92(4):761-94, viii. doi: 10.1016/j.mcna.2008.03.005. Review.

PubMed PMID: 18570942; PubMed Central PMCID: PMC2504411

21. Dart RC, Bailey E. Does therapeutic use of acetaminophen cause acute liver

failure? Pharmacotherapy. 2007 Sep;27(9):1219-30. Review. PubMed PMID: 17723075

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Filed under Acetaminophen toxicity, Liver failure