Acetaminophen Dose Does Not Predict Outcome in Acetaminophen-Induced Acute Liver Failure

Gregory, Blake; Larson, Anne M.; Reisch, Joan; Lee, William M.

doi:10.2310/jim.0b013e3181db8764

Cited by 33 publications

(19 citation statements)

References 29 publications

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“…This paradigm is consistent with recent observations 24 and may explain why the height of the AT peak per se is not predictive of encephalopathy and death. 25,26 More work is needed to clarify both AT release and clearance as well as differences between the time profiles of AST and ALT. Shown are the pooled serum AT doubling times and peak INR, grouped by the time needed for serum AT to reach 1,000 IU/L.…”

Section: Discussionmentioning

confidence: 99%

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When do the aminotransferases rise after acute acetaminophen overdose?

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Sivilotti

Langmann

et al. 2010

Clinical Toxicology

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Section: Discussionmentioning

confidence: 99%

“…This is important as AT alone is a poor predictor of mortality in APAP poisoning. 20,21 Our study is the most detailed analysis of AT kinetics in the early postingestion stage of hepatotoxicity. Singer et al described 19 patients, only 8 of whom met the traditional definition of hepatotoxicity (AT > 1,000 IU/L).…”

Section: Discussionmentioning

confidence: 99%

When do the aminotransferases rise after acute acetaminophen overdose?

Green

Sivilotti

Langmann

et al. 2010

Clinical Toxicology

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“…We conducted a retrospective analysis of all patients enrolled in the Acute Liver Failure Study Group (ALFSG) Registry between 1998‐2007 who were deemed to have either AI‐ALF, indeterminate ALF, or DI‐ALF by the site Principal Investigator (PI). The ALFSG study cohort and its outcomes have been previously described . A total of 361 consecutive patients were enrolled with ALF.…”

Section: Methodsmentioning

confidence: 99%

Steroid use in acute liver failure

et al. 2013

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Background/Aims Drug-induced and indeterminate Acute Liver Failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced or indeterminate ALF, and whether this benefit varies according to the severity of illness. Methods We conducted a retrospective analysis of autoimmune, indeterminate and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). Results 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% vs. 66%, p=0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of MELD (MELD > 40, survival 30% vs. 57%, p=0.03). In multivariable analysis controlling for steroid use and diagnosis, age (OR 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07) and pH<7.4 (OR 3.09) were significantly associated with mortality. Though steroid use was associated with a marginal benefit in SS overall (35% v. 23%, p=0.047), this benefit did not persistent in multivariable analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and ALT (1.02) were the only significant predictors of SS. Conclusions Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores.

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“…Once GSH stores are depleted, residual free NAPQI reacts with cellular components and causes injury to APAP‐metabolizing hepatocytes 6, 7. Early administration of the GSH precursor, N‐acetylcysteine (N‐Ac), ideally within 12 hours of overdose, prevents life‐threatening liver injury and ensures recovery 8. Later administration may limit the liver injury, but its utility decreases with time 9.…”

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confidence: 99%

Mathematical modeling of liver injury and dysfunction after acetaminophen overdose: Early discrimination between survival and death

et al. 2012

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Acetaminophen (APAP) is the leading cause of acute liver injury in the developed world. Timely administration of N-acetylcysteine (N-Ac) prevents the progression of serious liver injury and disease, whereas failure to administer N-Ac within a critical time frame allows disease progression and in the most severe cases may result in liver failure or death. In this situation, liver transplantation may be the only life-saving measure. Thus, the outcome of an APAP overdose depends on the size of the overdose and the time to first administration of N-Ac. We developed a system of differential equations to describe acute liver injury due to APAP overdose. The Model for Acetaminophen-induced Liver Damage (MALD) uses a patient's aspartate aminotransferase (AST), alanine aminotransferase (ALT), and international normalized ratio (INR) measurements on admission to estimate overdose amount, time elapsed since overdose, and outcome. The mathematical model was then tested on 53 patients from the University of Utah. With the addition of serum creatinine, eventual death was predicted with 100% sensitivity, 91% specificity, 67% positive predictive value (PPV), and 100% negative predictive value (NPV) in this retrospective study. Using only initial AST, ALT, and INR measurements, the model accurately predicted subsequent laboratory values for the majority of individual patients. This is the first dynamical rather than statistical approach to determine poor prognosis in patients with life-threatening liver disease due to APAP overdose. Conclusion: MALD provides a method to estimate overdose amount, time elapsed since overdose, and outcome from patient laboratory values commonly available on admission in cases of acute liver failure due to APAP overdose and should be validated in multicenter prospective evaluation. (HEPATOLOGY 2012;56:727-734)

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Acetaminophen Dose Does Not Predict Outcome in Acetaminophen-Induced Acute Liver Failure

Cited by 33 publications

References 29 publications

When do the aminotransferases rise after acute acetaminophen overdose?

When do the aminotransferases rise after acute acetaminophen overdose?

Steroid use in acute liver failure

Mathematical modeling of liver injury and dysfunction after acetaminophen overdose: Early discrimination between survival and death

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