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Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update
Open accessAbstract
Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes. APAP hepatotoxicity remains a global issue; in the United States, in particular, it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases. The pathophysiology, disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated, and adverse patient outcomes with increased morbidity and mortality continue to occur. Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients. Future research focus in this field may benefit from shifting towards obtaining antidotal knowledge at the molecular level, with focus on the underlying molecular signaling pathways.
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“Examples include alcohol148 and paracetamol,149 which damage pericentral hepatocytes and are responsible for the majority of fatal acute liver injury cases.”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [149]
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Citations
Cites
Efficacy of Oral N-Acetylcysteine in the Treatment of Acetaminophen Overdose
Smilkstein, M. J., Knapp, G. L., Kulig, K. W., & Rumack, B. H. (1988) · New England Journal of Medicine · doi:10.1056/nejm198812153192401 · Cited by 1,102
Jaeschke, H., McGill, M. R., & Ramachandran, A. (2012) · Drug Metabolism Reviews · doi:10.3109/03602532.2011.602688 · Cited by 972
(2018) · doi:10.1001/jama · Cited by 932
McGill, M. R., Sharpe, M. R., Williams, C. D., Taha, M., Curry, S. C., & Jaeschke, H. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59755 · Cited by 764
McGill, M. R., & Jaeschke, H. (2013) · Pharmaceutical Research · doi:10.1007/s11095-013-1007-6 · Cited by 703
Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning.
Prescott, L. F., Illingworth, R. N., Critchley, J. A., Stewart, M. J., Adam, R. D., & Proudfoot, A. T. (1979) · BMJ · doi:10.1136/bmj.2.6198.1097 · Cited by 667
Aminotransferase Elevations in Healthy Adults Receiving 4 Grams of Acetaminophen Daily
Watkins, P. B., Kaplowitz, N., Slattery, J. T., Colonese, C. R., Colucci, S. V., Stewart, P. W., & Harris, S. (2006) · JAMA · doi:10.1001/jama.296.1.87 · Cited by 631
Intravenous N-acetylcysteine: still the treatment of choice for paracetamol poisoning.
Prescott, L. F., Illingworth, R. N., Critchley, J., & Proudfoot, A. T. (1980) · BMJ · doi:10.1136/bmj.280.6206.46-b · Cited by 625
Improvement by Acetylcysteine of Hemodynamics and Oxygen Transport in Fulminant Hepatic Failure
Harrison, P. M., Wendon, J. A., Gimson, A. E. S., Alexander, G. J. M., & Williams, R. (1991) · New England Journal of Medicine · doi:10.1056/nejm199106273242604 · Cited by 585
Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity
Jaeschke, H., Williams, C. D., Ramachandran, A., & Bajt, M. L. (2011) · Liver International · doi:10.1111/j.1478-3231.2011.02501.x · Cited by 478
Acetylcysteine for Acetaminophen Poisoning
Heard, K. J. (2008) · New England Journal of Medicine · doi:10.1056/nejmct0708278 · Cited by 471
Association of Acetaminophen Hepatotoxicity With Fasting and Ethanol Use
Whitcomb, D. C. (1994) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1994.03520230055038 · Cited by 470
Herbal medication: potential for adverse interactions with analgesic drugs
Abebe, W. (2002) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1046/j.1365-2710.2002.00444.x · Cited by 425
Acetaminophen-induced nephrotoxicity: Pathophysiology, clinical manifestations, and management
Mazer, M., & Perrone, J. (2008) · Journal of Medical Toxicology · doi:10.1007/bf03160941 · Cited by 399
Acetaminophen Hepatotoxicity and Acute Liver Failure
Chun, L. J., Tong, M. J., Busuttil, R. W., & Hiatt, J. R. (2009) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31818a3854 · Cited by 348
Acetaminophen Hepatotoxicity: The First 35 Years
Rumack, B. H. (2002) · Journal of Toxicology Clinical Toxicology · doi:10.1081/clt-120002882 · Cited by 333
Liu, Z., Govindarajan, S., & Kaplowitz, N. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.08.053 · Cited by 328
Acetaminophen-related Hepatotoxicity
Bunchorntavakul, C., & Reddy, K. R. (2013) · Clinics in Liver Disease · doi:10.1016/j.cld.2013.07.005 · Cited by 322
Mechanisms of drug-induced liver injury
Yuan, L., & Kaplowitz, N. (2013) · Clinics in Liver Disease · doi:10.1016/j.cld.2013.07.002 · Cited by 322
Paracetamol (acetaminophen) poisoning
Thomas, S. H. L. (1993) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(93)90023-7 · Cited by 264
A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States
Blieden, M. B., Paramore, L. C., Shah, D., & Ben-Joseph, R. H. (2014) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2014.904744 · Cited by 262
Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity.
Lauterburg, B. H., & Velez, M. E. (1988) · Gut · doi:10.1136/gut.29.9.1153 · Cited by 258
Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine
de Andrade, K. Q., Moura, F. A., dos Santos, J. M., de Araújo, O. R. P., Santos, J. D. F., & Goulart, M. O. F. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161226225 · Cited by 258
Mechanisms of acetaminophen-induced cell death in primary human hepatocytes
Xie, Y., McGill, M. R., Dorko, K., Kumer, S. C., Schmitt, T. M., Forster, J., & Jaeschke, H. (2014) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2014.05.010 · Cited by 250
Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity
Schmidt, L. E., & Dalhoff, K. (2002) · Hepatology · doi:10.1053/jhep.2002.35069 · Cited by 235
Acetaminophen Poisoning: an Evidence-Based Consensus Guideline for Out-of-Hospital Management
Dart, R. C., Erdman, A. R., Olson, K. R., Christianson, G., Manoguerra, A. S., Chyka, P. A., Caravati, E. M., Wax, P. M., Keyes, D. C., Woolf, A. D., et al. (2006) · Clinical Toxicology · doi:10.1080/15563650500394571 · Cited by 196
Bailey, B., Amre, D. K., & Gaudreault, P. (2003) · Critical Care Medicine · doi:10.1097/00003246-200301000-00048 · Cited by 194
Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic failure.
Harrison, P., O’Grady, J. G., Keays, R. T., Alexander, G., & Williams, R. L. (1990) · BMJ · doi:10.1136/bmj.301.6758.964 · Cited by 169
Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity
Schmidt, L. E., Dalhoff, K., & Poulsen, H. E. (2002) · Hepatology · doi:10.1053/jhep.2002.32148 · Cited by 167
Kerr, F., Dawson, A. H., Whyte, I. M., Buckley, N. A., Murray, L., Graudins, A., Chan, B. S. H., & Trudinger, B. (2005) · Annals of Emergency Medicine · doi:10.1016/j.annemergmed.2004.08.040 · Cited by 162
McGill, M. R., Staggs, V. S., Sharpe, M. R., Lee, W. M., & Jaeschke, H. (2014) · Hepatology · doi:10.1002/hep.27265 · Cited by 148
Drug‐related Hepatotoxicity and Acute Liver Failure
Murray, K. F., Hadžić, N., Wirth, S., Bassett, M. D., & Kelly, D. A. (2008) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e3181709464 · Cited by 143
Inter‐subject and ethnic differences in paracetamol metabolism.
Critchley, J., Nimmo, G. R., Gregson, C., Woolhouse, N. M., & Prescott, L. (1986) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1986.tb02953.x · Cited by 140
Rumack, B. H. (2004) · Hepatology · doi:10.1002/hep.20300 · Cited by 139
Thulin, P., Nordahl, G., Gry, M., Yimer, G., Aklillu, E., Makonnen, E., Aderaye, G., Lindquist, L., Mattsson, C. M., Ekblom, B. T., et al. (2013) · Liver International · doi:10.1111/liv.12322 · Cited by 123
Paracetamol metabolism and related genetic differences
Zhao, L., & Pickering, G. P. (2010) · Drug Metabolism Reviews · doi:10.3109/03602532.2010.527984 · Cited by 120
McGill, M. R., & Jaeschke, H. (2014) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.920823 · Cited by 119
Xie, Y., Ramachandran, A., Breckenridge, D. G., Liles, J. T., Lebofsky, M., Farhood, A. I., & Jaeschke, H. (2015) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2015.03.019 · Cited by 113
Drug-Induced Liver Injury: Review Article
Bleibel, W., Kim, S. H., D'Silva, K. J., & Lemmer, E. R. (2007) · Digestive Diseases and Sciences · doi:10.1007/s10620-006-9472-y · Cited by 109
Systematic review: prognostic tests of paracetamol‐induced acute liver failure
CRAIG, D. G. N., Ford, A. C., Hayes, P. C., & Simpson, K. J. (2010) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2010.04279.x · Cited by 108
Role of inflammation in the mechanism of acetaminophen-induced hepatotoxicity
Jaeschke, H. (2005) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.1.3.389 · Cited by 93
Woolbright, B. L., McGill, M. R., Staggs, V. S., Winefield, R. D., Gholami, P., Olyaee, M. S., Sharpe, M. R., Curry, S. C., Lee, W. M., Jaeschke, H., et al. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kfu195 · Cited by 88
Sulforaphane protects against acetaminophen-induced hepatotoxicity
Noh, J., Kim, Y., Hwang, J. H., Choi, D., Kim, K., Oh, W. K., & Lee, C. (2015) · Food and Chemical Toxicology · doi:10.1016/j.fct.2015.03.020 · Cited by 87
Mennecozzi, M., Landesmann, B., Palosaari, T., Harris, G., & Whelan, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122786 · Cited by 85
Cholongitas, Ε., Theocharidou, E., Vasianopoulou, P., Betrosian, A. P., Shaw, S., Patch, D., O’Beirne, J. P., Agarwal, B., & Burroughs, A. K. (2011) · Liver Transplantation · doi:10.1002/lt.23370 · Cited by 84
Advances in the management of acute liver failure
Wang, D. (2013) · World Journal of Gastroenterology · doi:10.3748/wjg.v19.i41.7069 · Cited by 80
Underhill, T. J., Greene, M. K., & Dove, A. F. (1990) · Emergency Medicine Journal · doi:10.1136/emj.7.3.148 · Cited by 79
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
Acetaminophen Overdose in Pregnancy
Wilkes, J. M., Clark, L. E., & Herrera, J. L. (2005) · Southern Medical Journal · doi:10.1097/01.smj.0000184792.15407.51 · Cited by 77
Xie, Y., McGill, M. R., Cook, S. F., Sharpe, M. R., Winefield, R. D., Wilkins, D. G., Rollins, D. E., & Jaeschke, H. (2015) · Xenobiotica · doi:10.3109/00498254.2015.1026426 · Cited by 77
Jiang, Y., Fan, X., Wang, Y., Chen, P., Zeng, H., Tan, H., Gonzalez, F. J., Huang, M., & Bi, H. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kfu216 · Cited by 76
Patient Perception and Knowledge of Acetaminophen in a Large Family Medicine Service
Herndon, C. M., & Dankenbring, D. M. (2014) · Journal of Pain & Palliative Care Pharmacotherapy · doi:10.3109/15360288.2014.908993 · Cited by 70
Fontana, R. J., Meinzer, C., Durkalski, V., Rangnekar, A. S., Reddy, K. R., Stravitz, R. T., McGuire, B. M., Davern, T. J., Reuben, A., Liou, I. W., et al. (2014) · Liver International · doi:10.1111/liv.12632 · Cited by 68
Clark, R. K., Fisher, J. E., SKETRIS, I. S., & Johnston, G. M. (2012) · BMC Clinical Pharmacology · doi:10.1186/1472-6904-12-11 · Cited by 68
Acetaminophen Metabolism in Patients with Different Cytochrome P‐4502E1 Genotypes
Ueshima, Y., Tsutsumi, M., Takase, S., Matsuda, Y., & Kawahara, H. (1996) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1996.tb01722.x · Cited by 68
Paracetamol (acetaminophen) poisoning.
Buckley, N., & Eddleston, M. (2002) · PubMed Central · Cited by 53
Michna, E., Duh, M. S., Korves, C., & Dahl, J. L. (2010) · Pain Medicine · doi:10.1111/j.1526-4637.2010.00811.x · Cited by 53
Zhao, P., & Slattery, J. T. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.12.1413 · Cited by 52
Waring, W. S., Stephen, A. F., Malkowska, A. M., & Robinson, O. D. G. (2008) · Academic Emergency Medicine · doi:10.1111/j.1553-2712.2007.00019.x · Cited by 50
Decreased glutathione in patients with anorexia nervosa. Risk factor for toxic liver injury?
Zenger, F., Russmann, S., Junker, E., Wüthrich, C., Bui, M. H., & Lauterburg, B. H. (2004) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1601772 · Cited by 47
Krenzelok, E. P., & Royal, M. A. (2012) · Drugs in R&D · doi:10.2165/11633010-000000000-00000 · Cited by 45
A Pharmacokinetic Comparison of Acetaminophen Products (Tylenol Extended Relief vs Regular Tylenol)
Douglas, D. R., Sholal, J. B., & Smilkstein, M. J. (1996) · Academic Emergency Medicine · doi:10.1111/j.1553-2712.1996.tb03508.x · Cited by 44
Low rates of hepatotoxicity among Asian patients with paracetamol overdose: a review of 1024 cases
Marzilawati, A.-R., Ngau, Y. Y., & Mahadeva, S. (2012) · BMC Pharmacology and Toxicology · doi:10.1186/2050-6511-13-8 · Cited by 42
Character and Temporal Evolution of Apoptosis in Acetaminophen-Induced Acute Liver Failure*
Possamai, L. A., McPhail, M. J. W., Quaglia, A., Zingarelli, V., Abeles, R. D., Tidswell, R., Puthucheary, Z., Rawal, J., Karvellas, C. J., Leslie, E. M., et al. (2013) · Critical Care Medicine · doi:10.1097/ccm.0b013e31829791a2 · Cited by 42
Can AST/ALT ratio indicate recovery after acute paracetamol poisoning?
McGovern, A. J., Vitkovitsky, I., Jones, D. L., & Mullins, M. E. (2015) · Clinical Toxicology · doi:10.3109/15563650.2015.1006399 · Cited by 38
Hypophosphataemia in acute liver failure.
Dawson, D. J., Babbs, C., Warnes, T. W., & Neary, R. H. (1987) · BMJ · doi:10.1136/bmj.295.6609.1312 · Cited by 38
Influence of Age-Dependent Pharmacokinetics and Metabolism on Acetaminophen Hepatotoxicity
Rumore, M. M., & Blaiklock, R. G. (1992) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600810302 · Cited by 37
Unintentional Chronic Acetaminophen Poisoning During Pregnancy Resulting in Liver Transplantation
Thornton, S. L., & Minns, A. B. (2012) · Journal of Medical Toxicology · doi:10.1007/s13181-012-0218-2 · Cited by 36
Cytochrome P450-derived versus mitochondrial oxidant stress in acetaminophen hepatotoxicity
Jaeschke, H., & McGill, M. R. (2015) · Toxicology Letters · doi:10.1016/j.toxlet.2015.04.002 · Cited by 36
Serotonin Deficiency Exacerbates Acetaminophen-Induced Liver Toxicity In Mice
Zhang, J., Song, S., Pang, Q., Zhang, R., Zhou, L., Liu, S., Meng, F., Wu, Q., & Liu, C. (2015) · Scientific Reports · doi:10.1038/srep08098 · Cited by 34
Paracetamol poisoning - impact of pack size restrictions
Hughes, B., Durran, A. C., Langford, N. J., & Mutimer, D. (2003) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1046/j.1365-2710.2003.00497.x · Cited by 33
Targeting signal transduction pathways which regulate necrosis in acetaminophen hepatotoxicity
Kaplowitz, N., Win, S., Than, T. A., Liu, Z., & Dara, L. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.050 · Cited by 32
Antoine, D. J., Sabbisetti, V. S., Francis, B., Jorgensen, A., Craig, D. G. N., Simpson, K. J., Bonventre, J. V., Park, B. K., & Dear, J. W. (2015) · Hepatology · doi:10.1002/hep.27857 · Cited by 30
Hemorrhagic pancreatitis associated with acetaminophen overdose.
Caldarola, V., Jm, H., Ah, H., Ab, B., Kulig, K. W., & Rumack, B. H. (1986) · PubMed · Cited by 29
Herbal extracts as hepatoprotectants against acetaminophen hepatotoxicity
Jaeschke, H. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i19.2448 · Cited by 28
False Positive Acetaminophen Levels Associated with Hyperbilirubinemia
Beuhler, M. C., & Curry, S. C. (2005) · Clinical Toxicology · doi:10.1081/clt-57853 · Cited by 20
Serum phosphate is not a reliable early predictor of outcome in paracetamol induced hepatotoxicity
Ng, K. L., Davidson, J. S., & Bathgate, A. J. (2004) · Liver Transplantation · doi:10.1002/lt.20022 · Cited by 19
Acetaminophen overdose: What practitioners need to know
Bari, K., & Fontana, R. J. (2014) · Clinical Liver Disease · doi:10.1002/cld.373 · Cited by 16
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Metadata
- Authors
- Yoon, E. D., Babar, A., Choudhary, M. M., Kutner, M., & Pyrsopoulos, N.
- Affiliations
- University Hospital, Newark (US)
- Venue
- Journal of Clinical and Translational Hepatology
- Publisher
- Xia & He Publishing
- Published
- 2016-06-17
- Volume
- 4
- Issue
- 2
- Pages
- 131-42
- ISSN
- 2225-0719 (ISSN-L)
- 2310-8819
- PMC
- PMC4913076
- OpenAlex
- W2461975652
- Cited by
- 744
- References
- 78
- Citations by year
- 2026: 25 · 2025: 62 · 2024: 97 · 2023: 92 · 2022: 96 · 2021: 90 · 2020: 86 · 2019: 78 · 2018: 68 · 2017: 40 · 2016: 8
- FWCI
- 11.42
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of Clinical and Translational Hepatology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Emergency Medicine › Poisoning and overdose treatments
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- acetaminophen hepatotoxicity, acetaminophen overdose, acute liver failure, liver transplantation, molecular pathways, antidotes
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