Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update

Eric D. Yoon; Arooj Babar; Moaz Maqbool Choudhary; Matthew Kutner; Nikolaos Pyrsopoulos

doi:10.14218/jcth.2015.00052

Cited by 744Drug-Induced Hepatotoxicity and ProtectionPoisoning and overdose treatmentsLiver Disease Diagnosis and Treatment

Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update

Open access

Eric D. Yoon, Arooj Babar, Moaz Maqbool Choudhary, Matthew Kutner, Nikolaos Pyrsopoulos·2016·Journal of Clinical and Translational Hepatology

DOI 10.14218/jcth.2015.00052PMC PMC4913076

Open this paper in CoChat — free account Open PDF

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.14218/jcth.2015.00052

Cites

78 of 78 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Alcohol and paracetamol damage pericentral hepatocytes and are responsible for the majority of fatal acute liver injury cases.
“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]
The General approach and diagnostic tools section says acetaminophen causes its greatest liver injury in zone 3, consistent with damage to pericentral hepatocytes. Epidemiology identifies it as the most common cause of acute liver failure in the United States, but estimates it accounts for approximately 48% of diagnoses; it does not establish that paracetamol accounts for a majority of fatal acute liver injury cases. The separate citation attached to alcohol is not assessed here. (LLM, conf=0.88)
Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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 · see citing works
Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity
Jaeschke, H., McGill, M. R., & Ramachandran, A. (2012) · Drug Metabolism Reviews · doi:10.3109/03602532.2011.602688 · Cited by 972 · see citing works
Untitled work
(2018) · doi:10.1001/jama · Cited by 932 · see citing works
The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation
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 · see citing works
Metabolism and Disposition of Acetaminophen: Recent Advances in Relation to Hepatotoxicity and Diagnosis
McGill, M. R., & Jaeschke, H. (2013) · Pharmaceutical Research · doi:10.1007/s11095-013-1007-6 · Cited by 703 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Acetylcysteine for Acetaminophen Poisoning
Heard, K. J. (2008) · New England Journal of Medicine · doi:10.1056/nejmct0708278 · Cited by 463 · see citing works
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 · see citing works
Acetaminophen-induced nephrotoxicity: Pathophysiology, clinical manifestations, and management
Mazer, M., & Perrone, J. (2008) · Journal of Medical Toxicology · doi:10.1007/bf03160941 · Cited by 399 · see citing works
Acetaminophen Hepatotoxicity and Acute Liver Failure
Chun, L., Tong, M. J., Busuttil, R. W., & Hiatt, J. R. (2009) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31818a3854 · Cited by 345 · see citing works
Acetaminophen Hepatotoxicity: The First 35 Years
Rumack, B. H. (2002) · Journal of Toxicology Clinical Toxicology · doi:10.1081/clt-120002882 · Cited by 333 · see citing works
Innate immune system plays a critical role in determining the progression and severity of acetaminophen hepatotoxicity
Liu, Z., Govindarajan, S., & Kaplowitz, N. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.08.053 · Cited by 328 · 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
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 · see citing works
Paracetamol (acetaminophen) poisoning
Thomas, S. H. L. (1993) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(93)90023-7 · Cited by 264 · see citing works
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 · see citing works
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 · see citing works
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 253 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Fulminant hepatic failure secondary to acetaminophen poisoning: A systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation
Bailey, B., Amre, D. K., & Gaudreault, P. (2003) · Critical Care Medicine · doi:10.1097/00003246-200301000-00048 · Cited by 194 · see citing works
Serum mitochondrial biomarkers and damage-associated molecular patterns are higher in acetaminophen overdose patients with poor outcome
McGill, M. R., Staggs, V. S., Sharpe, M. R., Lee, W. M., & Jaeschke, H. (2014) · Hepatology · doi:10.1002/hep.27265 · Cited by 182 · see citing works
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 · see citing works
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 · see citing works
The Australasian Clinical Toxicology Investigators Collaboration Randomized Trial of Different Loading Infusion Rates of N-Acetylcysteine
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 · see citing works
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 · see citing works
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 · see citing works
Acetaminophen misconceptions
Rumack, B. H. (2004) · Hepatology · doi:10.1002/hep.20300 · Cited by 139 · see citing works
Keratin‐18 and micro RNA ‐122 complement alanine aminotransferase as novel safety biomarkers for drug‐induced liver injury in two human cohorts
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 · see citing works
Mechanistic biomarkers in acetaminophen-induced hepatotoxicity and acute liver failure: from preclinical models to patients
McGill, M. R., & Jaeschke, H. (2014) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.920823 · Cited by 119 · see citing works
Paracetamol metabolism and related genetic differences
Zhao, L., & Pickering, G. P. (2010) · Drug Metabolism Reviews · doi:10.3109/03602532.2010.527984 · Cited by 115 · see citing works
Inhibitor of apoptosis signal-regulating kinase 1 protects against acetaminophen-induced liver injury
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Glycodeoxycholic Acid Levels as Prognostic Biomarker in Acetaminophen-Induced Acute Liver Failure Patients
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 · see citing works
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 · see citing works
Sex Differences in Liver Toxicity—Do Female and Male Human Primary Hepatocytes React Differently to Toxicants In Vitro?
Mennecozzi, M., Landesmann, B., Palosaari, T., Harris, G., & Whelan, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122786 · Cited by 85 · see citing works
Comparison of the sequential organ failure assessment score with the King's College Hospital criteria and the model for end-stage liver disease score for the prognosis of acetaminophen-induced acute liver failure#
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 · see citing works
A comparison of the efficacy of gastric lavage, ipecacuanha and activated charcoal in the emergency management of paracetamol overdose.
Underhill, T. J., Greene, M. K., & Dove, A. F. (1990) · Emergency Medicine Journal · doi:10.1136/emj.7.3.148 · Cited by 80 · see citing works
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 · 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
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 · see citing works
Time course of acetaminophen-protein adducts and acetaminophen metabolites in circulation of overdose patients and in HepaRG cells
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 · see citing works
Schisandrol B Protects Against Acetaminophen-Induced Hepatotoxicity by Inhibition of CYP-Mediated Bioactivation and Regulation of Liver Regeneration
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 · see citing works
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 · see citing works
Two‐year outcomes in initial survivors with acute liver failure: results from a prospective, multicentre study
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 · see citing works
Population prevalence of high dose paracetamol in dispensed paracetamol/opioid prescription combinations: an observational study
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 · see citing works
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 · see citing works
Paracetamol (acetaminophen) poisoning.
Buckley, N., & Eddleston, M. (2002) · PubMed Central · Cited by 53 · see citing works
Removal of Opioid/Acetaminophen Combination Prescription Pain Medications: Assessing the Evidence for Hepatotoxicity and Consequences of Removal of These Medications
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 · see citing works
Effects of Ethanol Dose and Ethanol Withdrawal on Rat Liver Mitochondrial Glutathione: Implication of Potentiated Acetaminophen Toxicity in Alcoholics
Zhao, P., & Slattery, J. T. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.12.1413 · Cited by 52 · see citing works
Acute Ethanol Coingestion Confers a Lower Risk of Hepatotoxicity after Deliberate Acetaminophen Overdose
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 · see citing works
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 · see citing works
Confusion
Krenzelok, E. P., & Royal, M. A. (2012) · Drugs in R&D · doi:10.2165/11633010-000000000-00000 · Cited by 45 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Circulating Kidney Injury Molecule 1 Predicts Prognosis and Poor Outcome in Patients With Acetaminophen‐Induced Liver Injury
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 · see citing works
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 · see citing works
Herbal extracts as hepatoprotectants against acetaminophen hepatotoxicity
Jaeschke, H. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i19.2448 · Cited by 28 · see citing works
False Positive Acetaminophen Levels Associated with Hyperbilirubinemia
Beuhler, M. C., & Curry, S. C. (2005) · Clinical Toxicology · doi:10.1081/clt-57853 · Cited by 20 · see citing works
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 · see citing works
Acetaminophen overdose: What practitioners need to know
Bari, K., & Fontana, R. J. (2014) · Clinical Liver Disease · doi:10.1002/cld.373 · Cited by 16 · see citing works

Flagged first, then by citations

Sorted by citations

Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders
Chopyk, D. M., & Grakoui, A. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.04.077 · Cited by 495 · see citing works
Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms
Dar, W. A., Sullivan, E., Bynon, J. S., Eltzschig, H. K., & Ju, C. (2019) · Liver International · doi:10.1111/liv.14091 · Cited by 401 · see citing works
Abnormal liver enzymes: A review for clinicians
Kalas, M. A., Chavez, L., León, M., Taweesedt, P. T., & Surani, S. (2021) · World Journal of Hepatology · doi:10.4254/wjh.v13.i11.1688 · Cited by 334 · see citing works
Alcoholic Liver Disease: Alcohol Metabolism, Cascade of Molecular Mechanisms, Cellular Targets, and Clinical Aspects
Teschke, R. (2018) · Biomedicines · doi:10.3390/biomedicines6040106 · Cited by 244 · see citing works
Prediction of Drug-Induced Hepatotoxicity Using Long-Term Stable Primary Hepatic 3D Spheroid Cultures in Chemically Defined Conditions
Vorrink, S. U., Zhou, Y., Ingelman-Sundberg, M., & Lauschke, V. M. (2018) · Toxicological Sciences · doi:10.1093/toxsci/kfy058 · Cited by 187 · see citing works
Pain Management in Thoracic Surgery
Marshall, K., & McLaughlin, K. (2020) · Thoracic surgery clinics/Thorac. surg. clin. · doi:10.1016/j.thorsurg.2020.03.001 · Cited by 183 · 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
Fluorescent probe for the imaging of superoxide and peroxynitrite during drug-induced liver injury
Wu, L., Liu, J., Tian, X., Groleau, R. R., Bull, S. D., Li, P., Tang, B., & James, T. D. (2021) · Chemical Science · doi:10.1039/d0sc05937d · Cited by 179 · see citing works
Hepatotoxic potentials of methotrexate: Understanding the possible toxicological molecular mechanisms
Ezhilarasan, D. (2021) · Toxicology · doi:10.1016/j.tox.2021.152840 · Cited by 177 · see citing works
Interventions for paracetamol (acetaminophen) overdose
Chiew, A. L., Gluud, C., Brok, J., & Buckley, N. A. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003328.pub3 · Cited by 170 · see citing works
A Broad‐Spectrum ROS‐Eliminating Material for Prevention of Inflammation and Drug‐Induced Organ Toxicity
Li, L., Guo, J., Wang, Y., Xiong, X., Tao, H., Li, J., Jia, Y., Hu, H., & Zhang, J. (2018) · Advanced Science · doi:10.1002/advs.201800781 · Cited by 150 · see citing works
Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems
Lee-Montiel, F. T., George, S. M., Gough, A., Sharma, A. D., Wu, J., DeBiasio, R., Vernetti, L. A., & Taylor, D. L. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217703978 · Cited by 141 · see citing works
N-Acetylcysteine: A potential therapeutic agent for SARS-CoV-2
Poe, F. L., & Corn, J. (2020) · Medical Hypotheses · doi:10.1016/j.mehy.2020.109862 · Cited by 130 · see citing works
Loss of Sam50 in hepatocytes induces cardiolipin‐dependent mitochondrial membrane remodeling to trigger mtDNA release and liver injury
Chen, L., Dong, J., Liao, S., Wang, S., Wu, Z., Zuo, M., Liu, B., Yan, C., Chen, Y., He, H., et al. (2022) · Hepatology · doi:10.1002/hep.32471 · Cited by 128 · see citing works
Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compoundsin vivo and in vitro
Wang, X., Wu, Q., Liu, A., Anadón, A., Rodríguez, J.-L., Martínez-Larrañaga, M.-R., Yuan, Z., & Martínez, M. (2017) · Drug Metabolism Reviews · doi:10.1080/03602532.2017.1354014 · Cited by 124 · see citing works
Single-cell spatial transcriptomics reveals a dynamic control of metabolic zonation and liver regeneration by endothelial cell Wnt2 and Wnt9b
Hu, S., Liu, S., Bian, Y., Poddar, M., Singh, S., Cao, C., McGaughey, J., Bell, A., Blazer, L. L., Adams, J. J., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100754 · Cited by 118 · see citing works
Gut Microbiome and Response to Cardiovascular Drugs
Tuteja, S., & Ferguson, J. F. (2019) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.119.002314 · Cited by 119 · see citing works
Mitochondrial–Lysosomal Axis in Acetaminophen Hepatotoxicity
Moles, A., Torres, S., Baulies, A., García‐Ruiz, C., & Fernández-Checa, J. C. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00453 · Cited by 116 · see citing works
4-Methylpyrazole protects against acetaminophen hepatotoxicity in mice and in primary human hepatocytes
Akakpo, J. Y., Ramachandran, A., Kandel, S. E., Ni, H., Kumer, S., Rumack, B. H., & Jaeschke, H. (2018) · Human & Experimental Toxicology · doi:10.1177/0960327118774902 · Cited by 111 · see citing works
The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury
Barbier‐Torres, L., Iruzubieta, P., Fernández‐Ramos, D., Delgado, T. C., Taibo, D., Guitiérrez-de-Juan, V., Varela‐Rey, M., Azkargorta, M., Navasa, N., Fernández‐Tussy, P., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01970-x · Cited by 110 · see citing works
Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases
Martinez‐Uña, M., López‐Mancheño, Y., Diéguez, C., Fernandez-Rojo, M. A., & Novelle, M. G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249368 · Cited by 115 · see citing works
Delayed Treatment With 4-Methylpyrazole Protects Against Acetaminophen Hepatotoxicity in Mice by Inhibition of c-Jun n-Terminal Kinase
Akakpo, J. Y., Ramachandran, A., Duan, L., Schaich, M. A., Jaeschke, M. W., Freudenthal, B. D., Ding, W.-X., Rumack, B. H., & Jaeschke, H. (2019) · Toxicological Sciences · doi:10.1093/toxsci/kfz077 · Cited by 105 · see citing works
Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury
Schneider, K. M., Elfers, C., Ghallab, A., Schneider, C. V., Galvez, E. J. C., Mohs, A., Gui, W., Candels, L. S., Wirtz, T. H., Zuehlke, S., et al. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2020.11.002 · Cited by 108 · see citing works
Hepatic Complications of Anorexia Nervosa
Rosen, E., Bakshi, N., Watters, A., Rosen, H. R., & Mehler, P. S. (2017) · Digestive Diseases and Sciences · doi:10.1007/s10620-017-4766-9 · Cited by 107 · see citing works
Animal and Organoid Models of Liver Fibrosis
Bao, Y., Wang, L., Pan, H., Zhang, T.-R., Chen, Y., Xu, S.-J., Mao, X., & Li, S.-W. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.666138 · Cited by 101 · see citing works
Acetaminophen-induced liver injury: Molecular mechanism and treatments from natural products
Liao, J., Lu, Q., Li, Z., Li, J., Zhao, Q., & Li, J. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1122632 · Cited by 100 · see citing works
Kaempferol protects against propacetamol-induced acute liver injury through CYP2E1 inactivation, UGT1A1 activation, and attenuation of oxidative stress, inflammation and apoptosis in mice
Tsai, M., Wang, Y., Lai, Y.-Y., Tsou, H., Liou, G., Ko, J., & Wang, S. (2018) · Toxicology Letters · doi:10.1016/j.toxlet.2018.03.024 · Cited by 99 · see citing works
The Preventive Effects and the Mechanisms of Action of Navel Orange Peel Hydroethanolic Extract, Naringin, and Naringenin in N-Acetyl-p-aminophenol-Induced Liver Injury in Wistar Rats
Ahmed, O. M., Fahim, H. I., Ahmed, H. Y., Al-Muzafar, H. M., Ahmed, R. R., Amin, K. A., El‐Nahass, E., & Abdelazeem, W. H. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2745352 · Cited by 96 · see citing works
Pharmacologic Stepwise Multimodal Approach for Postpartum Pain Management
(2021) · Obstetrics & Gynecology · doi:10.1097/aog.0000000000004517 · Cited by 98 · see citing works
Microphysiological heart–liver body-on-a-chip system with a skin mimic for evaluating topical drug delivery
de Mello, C. P. P., Carmona‐Moran, C. A., McAleer, C. W., Perez, J., Coln, E. A., Long, C. J., Oleaga, C., Riu, A., Note, R., Teissier, S., et al. (2020) · Lab on a Chip · doi:10.1039/c9lc00861f · Cited by 94 · see citing works
Drug-induced liver injury and anti-hepatotoxic effect of herbal compounds: a metabolic mechanism perspective
Rani, J., Dhull, S. B., Rose, P. K., & Kidwai, M. K. (2024) · Phytomedicine · doi:10.1016/j.phymed.2023.155142 · Cited by 91 · see citing works
Chronic Inflammatory Diseases and Green Tea Polyphenols
Oz, H. S. (2017) · Nutrients · doi:10.3390/nu9060561 · Cited by 90 · see citing works
DNL 104, a Centrally Penetrant RIPK 1 Inhibitor, Inhibits RIP 1 Kinase Phosphorylation in a Randomized Phase I Ascending Dose Study in Healthy Volunteers
Grievink, H. W., Heuberger, J. A. A. C., Huang, F., Chaudhary, R., Birkhoff, W. A. J., Tonn, G., Mosesova, S., Erickson, R., Moerland, M., Haddick, P. C. G., et al. (2019) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1615 · Cited by 88 · see citing works
Role of pyroptosis in liver diseases
Mamun, A. A., Wu, Y., Jia, C., Munir, F., Sathy, K. J., Sarker, T., Monalisa, I., Zhou, K., & Xiao, J. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106489 · Cited by 89 · see citing works
p53 Up‐regulated Modulator of Apoptosis Induction Mediates Acetaminophen‐Induced Necrosis and Liver Injury in Mice
Chen, D., Ni, H., Wang, L., Ma, X., Yu, J., Ding, W., & Zhang, L. (2018) · Hepatology · doi:10.1002/hep.30422 · Cited by 87 · see citing works
Self-medication practice with analgesics (NSAIDs and acetaminophen), and antibiotics among nursing undergraduates in University College Farasan Campus, Jazan University, KSA
Faqihi, A. H. M. A., & Sayed, S. F. (2021) · Annales Pharmaceutiques Françaises · doi:10.1016/j.pharma.2020.10.012 · Cited by 87 · see citing works
Calcium Signaling in Liver Injury and Regeneration
Oliva‐Vilarnau, N., Hankeová, S., Vorrink, S. U., Mkrtchian, S., Andersson, E. R., & Lauschke, V. M. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00192 · Cited by 84 · see citing works
Nanotechnology for pain management: Current and future therapeutic interventions
Bhansali, D., Teng, S. L., Lee, C. S., Schmidt, B. L., Bunnett, N. W., & Leong, K. W. (2021) · Nano Today · doi:10.1016/j.nantod.2021.101223 · Cited by 85 · see citing works
Human Family 1–4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update
Rendić, S., & Guengerich, F. P. (2021) · Archives of Toxicology · doi:10.1007/s00204-020-02971-4 · Cited by 85 · see citing works
Ameliorative and protective effects of ginger and its main constituents against natural, chemical and radiation-induced toxicities: A comprehensive review
Alsherbiny, M. A., Abd-Elsalam, W. H., Badawy, S. A. E., Taher, E. S., Farès, M., Torres, A. M., Chang, D., & Li, C. G. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.10.048 · Cited by 86 · see citing works
Medicinal Thiols: Current Status and New Perspectives
Pfaff, A. R., Beltz, J., King, E., & Nuran Ercal, A. (2019) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557519666191119144100 · Cited by 82 · see citing works
Kaempferol suppresses acetaminophen-induced liver damage by upregulation/activation of SIRT1
BinMowyna, M. N., & AlFaris, N. A. (2021) · Pharmaceutical Biology · doi:10.1080/13880209.2021.1877734 · Cited by 81 · see citing works
The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication
Ning, Q., Wu, D., Wang, X., Xi, D., Chen, T., Chen, G., Wang, H., Lü, H., Wang, M., Zhu, L., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00907-1 · Cited by 82 · see citing works
A review of the hepatoprotective effects of hesperidin, a flavanon glycoside in citrus fruits, against natural and chemical toxicities
Tabeshpour, J., Hosseinzadeh, H., Hashemzaei, M., & Karimi, G. (2020) · DARU Journal of Pharmaceutical Sciences · doi:10.1007/s40199-020-00344-x · Cited by 78 · see citing works
Cytochrome P450 Induction and Xeno‐Sensing Receptors Pregnane X Receptor, Constitutive Androstane Receptor, Aryl Hydrocarbon Receptor and Peroxisome Proliferator‐Activated Receptor α at the Crossroads of Toxicokinetics and Toxicodynamics
Hakkola, J., Bernasconi, C., Coecke, S., Richert, L., Andersson, T. B., & Pelkonen, O. (2018) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13004 · Cited by 75 · see citing works
Treating osteoarthritis pain: mechanisms of action of acetaminophen, nonsteroidal anti-inflammatory drugs, opioids, and nerve growth factor antibodies
D’Arcy, Y. M., Mantyh, P. W., Yaksh, T. L., Donevan, S. D., Hall, J. A., Sadrarhami, M. M., & Viktrup, L. (2021) · Postgraduate Medicine · doi:10.1080/00325481.2021.1949199 · Cited by 72 · 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
Zebrafish as a Useful Model System for Human Liver Disease
Shimizu, N., Shiraishi, H., & Hanada, T. (2023) · Cells · doi:10.3390/cells12182246 · Cited by 72 · see citing works
Hepatoprotective effects of berberine on acetaminophen-induced hepatotoxicity in mice
Zhao, Z., Wei, Q., Hua, W., Liu, Y., Liu, X., & Zhu, Y. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.04.175 · Cited by 73 · see citing works
NF‐κB and AMPK/PI3K/Akt signaling pathways are involved in the protective effects of Platycodon grandiflorum saponins against acetaminophen‐induced acute hepatotoxicity in mice
Leng, J., Wang, Z., Fu, C., Zhang, J., Ren, S., Hu, J., Jiang, S., Wang, Y., Chen, C., & Li, W. (2018) · Phytotherapy Research · doi:10.1002/ptr.6160 · Cited by 73 · see citing works
Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways
Wang, Z., Hao, W.-N., Hu, J., Mi, X.-J., Han, Y., Ren, S., Jiang, S., Wang, Y., Li, X., & Li, W. (2019) · Antioxidants · doi:10.3390/antiox8090395 · Cited by 71 · see citing works
4-methylpyrazole protects against acetaminophen-induced acute kidney injury
Akakpo, J. Y., Ramachandran, A., Orhan, H., Curry, S. C., Rumack, B. H., & Jaeschke, H. (2020) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2020.115317 · Cited by 74 · see citing works
Mouse Systems Genetics as a Prelude to Precision Medicine
Li, H., & Auwerx, J. H. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.01.004 · Cited by 68 · see citing works
Efficacy and safety of magnesium isoglycyrrhizinate injection in patients with acute drug‐induced liver injury: A phase II trial
Wang, Y., Wang, Z., Gao, M., Zhong, H., Chen, C., Yao, Y., Zhang, Z., Zhang, X., Li, F., Zhang, J., et al. (2019) · Liver International · doi:10.1111/liv.14204 · Cited by 66 · see citing works
Treatment of inflammatory bowel disease via green tea polyphenols: possible application and protective approaches
Rahman, S. U., Li, Y., Huang, Y., Zhu, L., Feng, S., Wu, J., & Wang, X. (2018) · Inflammopharmacology · doi:10.1007/s10787-018-0462-4 · Cited by 64 · see citing works
Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway
Dkhil, M. A., Moneim, A. E. A., Hafez, T. A., Mubaraki, M. A., Mohamed, W. F., THAGFAN, F. A., & Al‐Quraishy, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20040993 · Cited by 64 · see citing works
Drug Induced Liver Injury: Can Biomarkers Assist RUCAM in Causality Assessment?
Teschke, R., Schulze, J., Eickhoff, A., & Danan, G. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040803 · Cited by 63 · see citing works
Sestrins in Physiological Stress Responses
Kim, M., Kowalsky, A. H., & Lee, J. H. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-031620-092317 · Cited by 62 · see citing works
Impact of cell types and culture methods on the functionality of in vitro liver systems – A review of cell systems for hepatotoxicity assessment
Kyffin, J. A., Sharma, P., Leedale, J., Colley, H. E., Murdoch, C., Mistry, P., & Webb, S. D. (2018) · Toxicology in Vitro · doi:10.1016/j.tiv.2018.01.023 · Cited by 61 · see citing works
Medical large language models are susceptible to targeted misinformation attacks
Han, T., Nebelung, S., Khader, F., Wang, T., Müller-Franzes, G., Kuhl, C., Försch, S., Kleesiek, J., Haarburger, C., Bressem, K. K., et al. (2024) · npj Digital Medicine · doi:10.1038/s41746-024-01282-7 · Cited by 62 · 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
Noninvasive monitoring of hepatic glutathione depletion through fluorescence imaging and blood testing
Jiang, X., Zhou, Q., Du, B., Li, S., Huang, Y., Chi, Z., Lee, W. M., Yu, M., & Zheng, J. (2021) · Science Advances · doi:10.1126/sciadv.abd9847 · Cited by 57 · see citing works
VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis
Rizvi, F., Lee, Y., Díaz‐Aragon, R., Bawa, P., So, J., Florentino, R. M., Wu, S. Y., Sarjoo, A., Truong, E., Smith, A. R., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.10.008 · Cited by 59 · see citing works
Hepatoprotective activity of metformin: A new mission for an old drug?
Iranshahy, M., Rezaee, R., & Karimi, G. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.02.004 · Cited by 56 · see citing works
N-Acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals
Tieu, S., Charchoglyan, A., Paulsen, L., Wagter-Lesperance, L., Shandilya, U. K., Bridle, B. W., Mallard, B. A., & Karrow, N. A. (2023) · Antioxidants · doi:10.3390/antiox12101867 · Cited by 56 · 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
González-Ponce, H. A., Rincón‐Sánchez, A. R., Jaramillo‐Juárez, F., & Moshage, H. J. (2018) · Nutrients · doi:10.3390/nu10020117 · Cited by 54 · see citing works
Formononetin protects against acetaminophen-induced hepatotoxicity through enhanced NRF2 activity
Jin, F., Wan, C. C., Li, W., Yao, L., Zhao, H., Zou, Y., Peng, D., & Huang, W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0170900 · Cited by 54 · see citing works
Selective inhibition of cullin 3 neddylation through covalent targeting DCN1 protects mice from acetaminophen-induced liver toxicity
Zhou, H., Lü, J., Chinnaswamy, K., Stuckey, J. A., Liu, L., McEachern, D., Yang, C., Bernard, D., Shen, H., Rui, L., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22924-4 · Cited by 52 · see citing works
Selective FRET nano probe based on carbon dots and naphthalimide–isatin for the ratiometric detection of peroxynitrite in drug-induced liver injury
Wu, Y., Sun, L.-L., Han, H., He, X., Cao, W., & James, T. D. (2023) · Chemical Science · doi:10.1039/d3sc05010f · Cited by 52 · see citing works
A Scalable Approach for the Generation of Human Pluripotent Stem Cell-Derived Hepatic Organoids with Sensitive Hepatotoxicity Features
Sgodda, M., Dai, Z., Zweigerdt, R., Sharma, A. D., Ott, M., & Cantz, T. (2017) · Stem Cells and Development · doi:10.1089/scd.2017.0023 · Cited by 53 · see citing works
The effects of mitochondrial transplantation in acetaminophen-induced liver toxicity in rats
Ülger, Ö., Kubat, G. B., Çiçek, Z., Çelik, E., Atalay, Ö., Suvay, S., & Özler, M. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119669 · Cited by 52 · see citing works
2,3,4′,5-tetrahydroxystilbene-2-O-β-D-glucoside exacerbates acetaminophen-induced hepatotoxicity by inducing hepatic expression of CYP2E1, CYP3A4 and CYP1A2
Xu, S., Liu, J., Shi, J., Wang, Z., & Ji, L. (2017) · Scientific Reports · doi:10.1038/s41598-017-16688-5 · Cited by 50 · see citing works
Acetaminophen-Induced Liver Injury Alters Expression and Activities of Cytochrome P450 Enzymes in an Age-Dependent Manner in Mouse Liver
Bao, Y., Wang, P., Shao, X., Zhu, J., Xiao, J., Shi, J., Zhang, L., Zhu, H., Ma, X., Manautou, J. E., et al. (2020) · Drug Metabolism and Disposition · doi:10.1124/dmd.119.089557 · Cited by 50 · see citing works
Hepatoprotective properties of red betel (Piper crocatum Ruiz and Pav) leaves extract towards H2O2-induced HepG2 cells via anti-inflammatory, antinecrotic, antioxidant potency
Lister, I. N. E., Ginting, C. N., Girsang, E., Nataya, E. D., Azizah, A. M., & Widowati, W. (2020) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2020.08.007 · Cited by 50 · see citing works
Innovative use of shrimp shell powder in carbon paste electrode for the electrochemical detection of dopamine and paracetamol: Valorization, characterization and application
Achache, M., Idrissi, G. E., Seddik, N. B., Boumlasy, S. E., Kouda, I., Raissouni, I., Chaouket, F., Draoui, K., Bouchta, D., & Choukairi, M. (2024) · Microchemical Journal · doi:10.1016/j.microc.2024.110754 · Cited by 49 · see citing works
N-acetylcysteine treatment blunts liver failure-associated impairment of locomotor activity
Ommati, M. M., Jamshidzadeh, A., Niknahad, H., Mohammadi, H., Sabouri, S., Heidari, R., & Abdoli, N. (2017) · PharmaNutrition · doi:10.1016/j.phanu.2017.10.003 · Cited by 48 · see citing works
The Bile Acid Receptor GPBAR1 Modulates CCL2/CCR2 Signaling at the Liver Sinusoidal/Macrophage Interface and Reverses Acetaminophen-Induced Liver Toxicity
Biagioli, M., Carino, A., Fiorucci, C., Marchianò, S., Giorgio, C. D., Bordoni, M., Roselli, R., Baldoni, M., Distrutti, E., Zampella, A., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901427 · Cited by 48 · see citing works
Epigenetic Mechanisms Contribute to Intraindividual Variations of Drug Metabolism Mediated by Cytochrome P450 Enzymes
Jin, J., & Zhong, X. (2023) · Drug Metabolism and Disposition · doi:10.1124/dmd.122.001007 · Cited by 47 · see citing works
Drug-Induced Liver Injury
Hamilton, L. A., Collins‐Yoder, A., & Collins, R. E. (2016) · AACN Advanced Critical Care · doi:10.4037/aacnacc2016953 · Cited by 47 · see citing works
Sestrin2 protects against acetaminophen-induced liver injury
Kim, S. J., Kim, K. M., Yang, J. H., Cho, S. S., Kim, J. Y., Park, S. J., Lee, S., Ku, S., Cho, I. J., & Ki, S. H. (2017) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2017.02.002 · Cited by 47 · see citing works
Mitochondrial Membrane Potential Drives Early Change in Mitochondrial Morphology After Acetaminophen Exposure
Umbaugh, D. S., Nguyen, N. T., Jaeschke, H., & Ramachandran, A. (2021) · Toxicological Sciences · doi:10.1093/toxsci/kfaa188 · Cited by 47 · see citing works
Acetaminophen cytotoxicity in HepG2 cells is associated with a decoupling of glycolysis from the TCA cycle, loss of NADPH production, and suppression of anabolism
Behrends, V., Giskeødegård, G. F., Bravo-Santano, N., Letek, M., & Keun, H. C. (2018) · Archives of Toxicology · doi:10.1007/s00204-018-2371-0 · Cited by 45 · see citing works
Histopathological changes of acetaminophen-induced liver injury and subsequent liver regeneration in BALB/C and ICR mice
Muhammad-Azam, F., Nur-Fazila, S. H., Ain-Fatin, R., Mustapha, N. M., & Yimer, N. (2019) · Veterinary World · doi:10.14202/vetworld.2019.1682-1688 · Cited by 45 · see citing works
Acetaminophen induced hepatotoxicity: An overview of the promising protective effects of natural products and herbal formulations
Chilvery, S., Yelne, A., Khurana, A., Saifi, M. A., Bansod, S., Anchi, P., & Godugu, C. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154510 · Cited by 45 · see citing works
Reverse Engineering To Characterize Redox Properties: Revealing Melanin’s Redox Activity through Mediated Electrochemical Probing
Kang, M., Kim, E., Temoçin, Z., Li, J., Dadachova, E., Wang, Z., Panzella, L., Napolitano, A., Bentley, W. E., & Payne, G. F. (2018) · Chemistry of Materials · doi:10.1021/acs.chemmater.8b02428 · Cited by 43 · see citing works
Ferroptosis and Acetaminophen Hepatotoxicity: Are We Going Down Another Rabbit Hole?
Jaeschke, H., Adelusi, O. B., & Ramachandran, A. (2021) · Gene Expression · doi:10.3727/105221621x16104581979144 · Cited by 44 · see citing works
The Role of Liver Zonation in Physiology, Regeneration, and Disease
Panday, R., Monckton, C. P., & Khetani, S. R. (2022) · Seminars in Liver Disease · doi:10.1055/s-0041-1742279 · Cited by 44 · see citing works
Liver‐specific deficiency of unc‐51 like kinase 1 and 2 protects mice from acetaminophen‐induced liver injury
Sun, Y., Li, T. Y., Song, L., Zhang, C., Li, J., Lin, Z., Lin, S., & Lin, S. (2018) · Hepatology · doi:10.1002/hep.29759 · Cited by 43 · see citing works
Egyptian perspectives on potential risk of paracetamol/acetaminophen-induced toxicities: Lessons learnt during COVID-19 pandemic
Mostafa, E. M. A., Tawfik, A. M., & abdelrahman, K. M. (2022) · Toxicology Reports · doi:10.1016/j.toxrep.2022.03.035 · Cited by 43 · see citing works
Modeling drug-induced liver injury and screening for anti-hepatofibrotic compounds using human PSC-derived organoids
Wu, X., Jiang, D., Yang, Y. A., Li, S., & Ding, Q. (2023) · Cell Regeneration · doi:10.1186/s13619-022-00148-1 · Cited by 47 · see citing works
A sensitive sensing platform for acetaminophen based on palladium and multi-walled carbon nanotube composites and electrochemical detection mechanism
Wu, Y., Wu, Y., Lv, X., Wu, L., Ding, Y., Chen, C., Lv, J., Feng, S., Chen, S., & Hao, Q. (2019) · Materials Chemistry and Physics · doi:10.1016/j.matchemphys.2019.121977 · Cited by 43 · see citing works
Herbal Therapy for the Treatment of Acetaminophen-Associated Liver Injury: Recent Advances and Future Perspectives
Chang, L., Xu, D., Zhu, J., Ge, G., Kong, X., & Zhou, Y. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00313 · Cited by 46 · see citing works
Drug repurposing of N-acetyl cysteine as antiviral against dengue virus infection
Sreekanth, G. P., Panaampon, J., Suttitheptumrong, A., Chuncharunee, A., Bootkunha, J., Yenchitsomanus, P., & Limjindaporn, T. (2019) · Antiviral Research · doi:10.1016/j.antiviral.2019.03.011 · Cited by 42 · see citing works
Hepatoprotective effect of Pandanus odoratissimus seed extracts on paracetamol-induced rats
Sinaga, E., Fitrayadi, A., Asrori, A., Rahayu, S., Suprihatin, S., & Prasasty, V. (2021) · Pharmaceutical Biology · doi:10.1080/13880209.2020.1865408 · Cited by 34 · see citing works
Treatment of Drug-Induced Liver Injury
Teschke, R. (2022) · Biomedicines · doi:10.3390/biomedicines11010015 · Cited by 41 · see citing works
Abnormal Liver Biochemistry Tests and Acute Liver Injury in COVID-19 Patients: Current Evidence and Potential Pathogenesis
McGrowder, D. A., Miller, F. G., Cross, M. A., Anderson-Jackson, L., Bryan, S., & Dilworth, L. (2021) · Diseases · doi:10.3390/diseases9030050 · Cited by 40 · see citing works
Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1
Bai, Q., Yan, H., Sheng, Y., Jin, Y., Shi, L., Ji, L., & Wang, Z. (2017) · Toxicology · doi:10.1016/j.tox.2017.03.008 · Cited by 40 · see citing works
Progesterone receptor membrane component 1 (PGRMC1) binds and stabilizes cytochromes P450 through a heme-independent mechanism
McGuire, M. R., Mukhopadhyay, D., Myers, S. L., Mosher, E. P., Brookheart, R. T., Kammers, K., Sehgal, A., Alpergin, E. S. S., Wolfgang, M. J., Bumpus, N. N., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101316 · Cited by 40 · see citing works
Inhibition of p53 Sulfoconjugation Prevents Oxidative Hepatotoxicity and Acute Liver Failure
Xu, P., Xi, Y., Wang, P., Luka, Z., Xu, M., Tung, H., Wang, J., Ren, S., Feng, D., Gao, B., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.12.260 · Cited by 40 · see citing works

Authors: Yoon, E. D., Babar, A., Choudhary, M. M., Kutner, M., & Pyrsopoulos, N.
Affiliations: University Hospital, Newark (US)
ORCID: Moaz Maqbool Choudhary
Nikolaos Pyrsopoulos
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
DOI: 10.14218/jcth.2015.00052
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 · 2013: 1
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 › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords: acetaminophen hepatotoxicity, acetaminophen overdose, acute liver failure, liver transplantation, molecular pathways, antidotes

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks