Prognosis is related to the degree of encephalopathy, coagulopathy, and acidosis.[5]Fontana RJ, Liou I, Reuben A, et al. AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury. Hepatology. 2023 Mar 1;77(3):1036-65.
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Acetylcysteine is nearly 100% effective when started within 8 hours after ingestion.[4]Smilkstein MJ, Knapp GL, Kulig KW, et al. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose: analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988 Dec 15;319(24):1557-62.
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[85]Licata A, Minissale MG, Stankevičiūtė S, et al. N-acetylcysteine for preventing acetaminophen-induced liver injury: a comprehensive review. Front Pharmacol. 2022 Aug 10;13:828565.
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.828565/full
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Treatment delays beyond 8 hours are associated with stepwise increases in risk of hepatotoxicity, transplant, and death.[4]Smilkstein MJ, Knapp GL, Kulig KW, et al. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose: analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988 Dec 15;319(24):1557-62.
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[108]Sivilotti ML, Yarema MC, Juurlink DN, et al. A risk quantification instrument for acute acetaminophen overdose patients treated with N-acetylcysteine. Ann Emerg Med. 2005 Sep;46(3):263-71.
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Liver injury usually becomes maximal at 72-96 hours. Although most patients will recover, some may progress to have fulminant hepatic failure with encephalopathy, coma, and renal failure (hepatorenal syndrome), and rarely, hemorrhage.[53]Prescott LF, Critchley JA. The treatment of acetaminophen poisoning. Annu Rev Pharmacol Toxicol. 1983;23:87-101.
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[54]Flanagan RJ, Mant TG. Coma and metabolic acidosis early in severe acute paracetamol poisoning. Hum Toxicol. 1986 May;5(3):179-82.
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[55]Roth B, Woo O, Blanc P. Early metabolic acidosis and coma after acetaminophen ingestion. Ann Emerg Med. 1999 Apr;33(4):452-6.
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[56]Hamlyn AN, Douglas AP, James O. The spectrum of paracetamol (acetaminophen) overdose: clinical and epidemiological studies. Postgrad Med J. 1978 Jun;54(632):400-4.
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[57]Prescott LF, Proudfoot AT, Cregeen RJ. Paracetamol-induced acute renal failure in the absence of fulminant liver damage. Br Med J (Clin Res Ed). 1982 Feb 6;284(6313):421-2.
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In survivors, hepatic regeneration is normally rapid and complete, with normalization of liver function tests within 1 to 3 weeks.[62]Lesna M, Watson AJ, Douglas AP, et al. Evaluation of paracetamol-induced damage in liver biopsies: acute changes and follow-up findings. Virchows Arch A Pathol Anat Histol. 1976 Jul 21;370(4):333-44.
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[63]Portmann B, Talbot IC, Day DW, et al. Histopathological changes in the liver following a paracetamol overdose: correlation with clinical and biochemical parameters. J Pathol. 1975 Nov;117(3):169-81.
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[109]Baeg NJ, Bodenheimer HC Jr, Burchard K. Long-term sequellae of acetaminophen-associated fulminant hepatic failure: relevance of early histology. Am J Gastroenterol. 1988 May;83(5):569-71.
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Abnormalities of prothrombin time, glucose, lactate, creatinine, pH, and phosphate, are more important markers of prognosis than the degree aminotransferase elevation.[58]O'Grady JG, Alexander GJ, Hayllar KM, et al. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989 Aug;97(2):439-45.
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[59]Bailey B, Amre DK, Gaudreault P. Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Crit Care Med. 2003 Jan;31(1):299-305.
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In unselected patients, even without specific treatment, the prognosis is usually good with <10% developing hepatotoxicity; 1% acute renal failure; and a 1% to 2% mortality rate (due to hepatic failure).[53]Prescott LF, Critchley JA. The treatment of acetaminophen poisoning. Annu Rev Pharmacol Toxicol. 1983;23:87-101.
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An increased risk of severe hepatotoxicity and higher mortality has been reported in patients with staggered overdoses or delayed presentation.[110]Craig DG, Bates CM, Davidson JS, et al. Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity. Br J Clin Pharmacol. 2012 Feb;73(2):285-94.
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