Acute Liver Failure Including Acetaminophen Overdose

Fontana, Robert J.

doi:10.1016/j.mcna.2008.03.005

Cited by 249Drug-Induced Hepatotoxicity and ProtectionLiver Disease and TransplantationPoisoning and overdose treatments

Acute Liver Failure Including Acetaminophen Overdose

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Fontana, Robert J.·2008·Medical Clinics of North America

DOI 10.1016/j.mcna.2008.03.005PMC PMC2504411

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Abstract

Acute liver failure (ALF) is a dramatic, highly unpredictable clinical syndrome defined by the sudden onset of coagulopathy and encephalopathy. Acetaminophen overdose, the leading cause of ALF in the United States, has a 66% chance of recovery with early N-acetylcysteine treatment and supportive care. Cerebral edema and infectious complications are difficult to detect and treat in these patients and may cause irreversible brain damage and multiorgan failure. One-year survival after emergency liver transplantation is 70%, but 20% of listed patients die, highlighting the importance of early referral of patients who have ALF with a poor prognosis to a transplant center.

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Intentional and unintentional overdose emerged as a leading cause of acute liver failure in many countries and remains one of the most common causes of drug-induced liver injury worldwide.
“Intentional and unintentional overdose emerged as a leading cause of acute liver failure in many countries and remains one of the most common causes of drug-induced liver injury worldwide ( 12 – 14 ].”
From Paracetamol: A History of Assumptions, Errors, and Evidence Reversals in Pain Management (2026) · cites this paper as [12]
The Diagnosis of acetaminophen hepatotoxicity section (page unavailable) says acetaminophen overdose is the leading cause of acute liver failure in the United States and other Western countries. The Non-intentional acetaminophen overdose section (page unavailable) confirms that cases include overdoses without suicide intent. The paper does not establish that overdose is among the most common causes of drug-induced liver injury worldwide. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Severe toxicity of paracetamol has long been recognized, but it was historically dismissed as a distinct complication of acute overdose.
“Severe toxicity has long been recognized, but it was historically dismissed as a distinct complication of acute overdose [ 12 , 13 ].”
From Paracetamol: A History of Assumptions, Errors, and Evidence Reversals in Pain Management (2026) · cites this paper as [12]
The Diagnosis of acetaminophen hepatotoxicity section describes severe liver injury from acetaminophen and mentions underappreciation of its hepatotoxicity. It does not say that severe toxicity was historically dismissed as a distinct complication of acute overdose. (LLM, conf=0.78)
Experimental — accuracy not yet measured

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Drug-induced liver injury
Katarey, D. R., & Verma, S. (2016) · Clinical Medicine · doi:10.7861/clinmedicine.16-6-s104 · Cited by 339 · see citing works
Acetaminophen-related Hepatotoxicity
Bunchorntavakul, C., & Reddy, K. R. (2013) · Clinics in Liver Disease · doi:10.1016/j.cld.2013.07.005 · Cited by 322 · see citing works
Acute Liver Failure Guidelines
Shingina, A., Mukhtar, N. A., Wakim-Fleming, J., Alqahtani, S. A., Wong, R. J., Limketkai, B. N., Larson, A. M., & Grant, L. M. (2023) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000002340 · Cited by 233 · see citing works
An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure
Tuñón, M. J., Alvarez, M., Culebras, J. M., & González‐Gallego, J. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.3086 · Cited by 208 · see citing works
Acetaminophen Toxicity: Novel Insights Into Mechanisms and Future Perspectives
Ramachandran, A., & Jaeschke, H. (2017) · Gene Expression · doi:10.3727/105221617x15084371374138 · Cited by 211 · see citing works
Drug-induced liver injury: a comprehensive review
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Drug‐induced liver injury: Advances in mechanistic understanding that will inform risk management
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Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction
LeFort, K. R., Rungratanawanich, W., & Song, B.-J. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-05061-7 · Cited by 202 · see citing works
Acetaminophen (APAP or N-Acetyl-p-Aminophenol) and Acute Liver Failure
Bunchorntavakul, C., & Reddy, K. R. (2018) · Clinics in Liver Disease · doi:10.1016/j.cld.2018.01.007 · Cited by 180 · see citing works
Liver injury induced by paracetamol and challenges associated with intentional and unintentional use
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Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand
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The Role of Resveratrol in Liver Disease: A Comprehensive Review from In Vitro to Clinical Trials
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Hepatic 3D cultures but not 2D cultures preserve specific transporter activity for acetaminophen-induced hepatotoxicity
Schyschka, L., Sánchez, J. M., Wang, Z., Burkhardt, B., Müller‐Vieira, U., Zeilinger, K., Bachmann, A., Nadalin, S., Damm, G., & Nussler, A. K. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1080-y · Cited by 128 · see citing works
Naturally Occurring Nrf2 Activators: Potential in Treatment of Liver Injury
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Outcomes in liver transplantation: Does sex matter?
Sarkar, M. A., Watt, K. D. S., Terrault, N. A., & Berenguer, M. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.11.023 · Cited by 116 · see citing works
Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease
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Acetaminophen: Old drug, new warnings
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Lysosomal Iron Mobilization and Induction of the Mitochondrial Permeability Transition in Acetaminophen-Induced Toxicity to Mouse Hepatocytes
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Current etiological comprehension and therapeutic targets of acetaminophen-induced hepatotoxicity
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Resveratrol and liver disease: from bench to bedside and community
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Review article: the current management of acute liver failure
CRAIG, D. G. N., Lee, A., Hayes, P. C., & Simpson, K. J. (2009) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2009.04175.x · Cited by 103 · see citing works
Acetaminophen Induces Apoptosis in Rat Cortical Neurons
Posadas, I., Santos, P. R., Blanco, A., Muñoz‐Fernández, M. Á., & Ceña, V. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015360 · Cited by 106 · see citing works
Liver transplant associated with paracetamol overdose: results from the seven‐country SALT study
Gulmez, S. E., Larrey, D., Pageaux, G., Bernuau, J., Bissoli, F., Horsmans, Y., Thorburn, D., McCormick, P. A., Stricker, B., Toussi, M., et al. (2015) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12635 · Cited by 99 · see citing works
Orthopaedic management of the Ehlers–Danlos syndromes
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Generation of Carbon Monoxide Releasing Molecules (CO-RMs) as Drug Candidates for the Treatment of Acute Liver Injury: Targeting of CO-RMs to the Liver
Marques, A. R., Kromer, L., Gallo, D. J., Penacho, N., Rodrigues, S. S., Seixas, J. D., Bernardes, G. J. L., Reis, P. M., Otterbein, S. L., Ruggieri, R. A., et al. (2012) · Organometallics · doi:10.1021/om300360c · Cited by 83 · see citing works
Translocation of iron from lysosomes to mitochondria during acetaminophen-induced hepatocellular injury: Protection by starch-desferal and minocycline
Hu, J., Kholmukhamedov, A., Lindsey, C. C., Beeson, C. C., Jaeschke, H., & Lemasters, J. J. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.06.024 · Cited by 81 · see citing works
Role of Bile Acids in Liver Injury and Regeneration following Acetaminophen Overdose
Bhushan, B., Borude, P., Edwards, G., Walesky, C., Cleveland, J., Li, F., Ma, X., & Apte, U. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.07.012 · Cited by 79 · see citing works
Potential of extracellular microRNAs as biomarkers of acetaminophen toxicity in children
Yang, X., Salminen, W. F., Shi, Q., Greenhaw, J. J., Gill, P. S., Bhattacharyya, S., Beger, R. D., Mendrick, D. L., Mattes, W. B., & James, L. P. (2015) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2015.02.013 · Cited by 78 · see citing works
Toxicity by NSAIDs. Counteraction by Stable Gastric Pentadecapeptide BPC 157
Sikirić, P., Seiwerth, S., Ručman, R., Turković, B., Rokotov, D. S., Brčić, L., Sever, M., Kliček, R., Radić, B., Drmić, D., et al. (2012) · Current Pharmaceutical Design · doi:10.2174/1381612811306010076 · Cited by 77 · see citing works
Platelets and protease-activated receptor-4 contribute to acetaminophen-induced liver injury in mice
Miyakawa, K., Joshi, N., Sullivan, B. P., Albee, R., Brandenberger, C., Jaeschke, H., McGill, M. R., Scott, M. A., Ganey, P. E., Luyendyk, J. P., et al. (2015) · Blood · doi:10.1182/blood-2014-09-598656 · Cited by 75 · see citing works
Acetaminophen-induced Acute Liver Failure Is More Common and More Severe in Women
Rubin, J. B., Hameed, B., Gottfried, M., Lee, W. M., & Sarkar, M. A. (2017) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2017.11.042 · Cited by 75 · see citing works
Dose Predictions for Drug Design
Maurer, T. S., Smith, D. A., Beaumont, K. C., & Di, L. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01365 · Cited by 73 · see citing works
High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736).
Ilić, S., Drmić, D., Žarković, K., Kolenc, D., Coric, M., Brcic, L., Kliček, R., Radić, B., Sever, M., Djuzel, V., et al. (2010) · PubMed · Cited by 68 · see citing works
Protective effects of p-coumaric acid against acetaminophen-induced hepatotoxicity in mice
Cha, H., Lee, S., Lee, J. H., & Park, J. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.08.060 · Cited by 66 · see citing works
Acute liver failure: A review for emergency physicians
Montrief, T., Koyfman, A., & Long, B. (2018) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2018.10.032 · Cited by 61 · see citing works
Variability in opioid prescribing for children undergoing ambulatory surgery in the United States
Cleve, W. V., & Grigg, E. B. (2017) · Journal of Clinical Anesthesia · doi:10.1016/j.jclinane.2017.05.014 · Cited by 59 · see citing works
Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats
Ilić, S., Drmić, D., Žarković, K., Kolenc, D., Brčić, L., Radić, B., Djuzel, V., Blagaić, A. B., Romić, Ž., Džidić, S., et al. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.05.038 · Cited by 57 · see citing works
Exogenous exosomes from mice with acetaminophen-induced liver injury promote toxicity in the recipient hepatocytes and mice
Cho, Y., Seo, W., Kim, D., Moon, P., Kim, S., Lee, B.-H., Song, B., & Baek, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-34309-7 · Cited by 56 · see citing works
Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs
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Authors: Fontana, R. J.
Affiliations: University of Michigan (US)
Corresponding author: Fontana, Robert J.
ORCID: Fontana, Robert J.
Venue: Medical Clinics of North America
Publisher: Elsevier BV
Published: 2008-07
Volume: 92
Issue: 4
Pages: 761-794
ISSN: 0025-7125 (ISSN-L)
DOI: 10.1016/j.mcna.2008.03.005
PMC: PMC2504411
OpenAlex: W1979020366
Cited by: 249
References: 134
Citations by year: 2026: 7 · 2025: 8 · 2024: 8 · 2023: 16 · 2022: 9 · 2021: 26 · 2020: 19 · 2019: 18 · 2018: 19 · 2017: 18 · 2016: 15 · 2015: 13 · 2014: 14 · 2013: 11 · 2012: 9
FWCI: 1.88
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Medical Clinics of North America (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (5u01dk065184-22)
National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK-065184, UO1 DK058389-07, U01DK058369)
National Center for Research Resources (M01RR000042)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
Health Sciences › Medicine › Emergency Medicine › Poisoning and overdose treatments
Keywords: acute liver failure, acetaminophen overdose, N-acetylcysteine, coagulopathy, encephalopathy, cerebral edema, infectious complications, liver transplantation, survival after liver transplantation
MeSH terms: Acetaminophen, Humans, Prognosis, Liver Transplantation, Liver Failure, Acute, Analgesics, Non-Narcotic, Drug Overdose

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Acute Liver Failure Including Acetaminophen Overdose

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