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Accuracy of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity in modified-release paracetamol overdose.

Abstract The paracetamol-aminotransferase multiplication product (APAP × ALT) is a risk predictor of hepatotoxicity that is somewhat independent of time and type of ingestion. However, its accuracy following ingestion of modified-release formulations is not known, as the product has been derived and validated after immediate-release paracetamol overdoses.
PMID
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Authors

Mayor MeshTerms
Keywords

Acetaminophen

NAC

liver injury

risk

Journal Title clinical toxicology (philadelphia, pa.)
Publication Year Start



 

PMID- 28421844
OWN - NLM
STAT- MEDLINE
DA  - 20170419
DCOM- 20170425
LR  - 20170425
IS  - 1556-9519 (Electronic)
IS  - 1556-3650 (Linking)
VI  - 55
IP  - 5
DP  - 2017 Jun
TI  - Accuracy of the paracetamol-aminotransferase multiplication product to predict
      hepatotoxicity in modified-release paracetamol overdose.
PG  - 346-351
LID - 10.1080/15563650.2017.1290253 [doi]
AB  - CONTEXT: The paracetamol-aminotransferase multiplication product (APAP x ALT) is 
      a risk predictor of hepatotoxicity that is somewhat independent of time and type 
      of ingestion. However, its accuracy following ingestion of modified-release
      formulations is not known, as the product has been derived and validated after
      immediate-release paracetamol overdoses. OBJECTIVE: The aim of this retrospective
      cohort study was to evaluate the accuracy of the multiplication product to
      predict hepatotoxicity in a cohort of patients with modified-release paracetamol 
      overdose. METHODS: We assessed all patients with modified-release paracetamol
      overdose presenting to our hospital network from October 2009 to July 2016.
      Ingestion of a modified-release formulation was identified by patient self-report
      or retrieval of the original container. Hepatotoxicity was defined as peak
      alanine aminotransferase >/=1000 IU/L, and acute liver injury (ALI) as a doubling
      of baseline ALT to more than 50 IU/L. RESULTS: Of 1989 paracetamol overdose
      presentations, we identified 73 modified-release paracetamol exposures treated
      with acetylcysteine. Five patients developed hepatotoxicity, including one who
      received acetylcysteine within eight hours of an acute ingestion. No patient with
      an initial multiplication product <10,000 mg/L x IU/L developed hepatotoxicity
      (sensitivity 100% [95%CI 48%, 100%], specificity 97% [90%, 100%]). Specificity
      fell to 54% (95%CI: 34, 59%) at a product cut-off point <1500 mg/L x IU/L. When
      calculated within eight hours of ingestion, mild elevations of the multiplication
      product fell quickly on repeat testing in patients without ALI or hepatotoxicity.
      CONCLUSIONS: In modified-release paracetamol overdose treated with
      acetylcysteine, the paracetamol-aminotransferase multiplication product
      demonstrated similar accuracy and temporal profile to previous reports involving 
      mostly immediate-release formulations. Above a cut-point of 10,000 mg/L x IU/L,
      it was very strongly associated with the development of acute liver injury and
      hepatotoxicity, especially when calculated more than eight hours post-ingestion. 
      When below 1500 mg/L x IU/L the likelihood of developing hepatotoxicity was very 
      low. Persistently high serial multiplication product calculations were associated
      with the greatest risk of hepatotoxicity.
FAU - Wong, Anselm
AU  - Wong A
AD  - a Victorian Poisons Information Centre and Austin Toxicology Service , Heidelberg
      , Australia.
AD  - b School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences ,
      Monash University , Clayton , Australia.
FAU - Sivilotti, Marco L A
AU  - Sivilotti MLA
AD  - c Departments of Emergency Medicine and of Biomedical & Molecular Sciences ,
      Queen's University , Kingston , Canada.
FAU - Graudins, Andis
AU  - Graudins A
AD  - b School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences ,
      Monash University , Clayton , Australia.
AD  - d Emergency Medicine and Toxicology Research , Monash Health , Victoria ,
      Australia.
LA  - eng
PT  - Journal Article
DEP - 20170215
PL  - England
TA  - Clin Toxicol (Phila)
JT  - Clinical toxicology (Philadelphia, Pa.)
JID - 101241654
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 362O9ITL9D (Acetaminophen)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - AIM
SB  - IM
MH  - Acetaminophen/blood/*poisoning
MH  - Acetylcysteine/therapeutic use
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alanine Transaminase/*blood
MH  - Analgesics, Non-Narcotic/blood/*poisoning
MH  - Chemical and Drug Induced Liver Injury/blood/*diagnosis/drug therapy
MH  - Drug Overdose/*blood/diagnosis/drug therapy
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Sensitivity and Specificity
MH  - Young Adult
OTO - NOTNLM
OT  - Acetaminophen
OT  - NAC
OT  - liver injury
OT  - risk
EDAT- 2017/04/20 06:00
MHDA- 2017/04/26 06:00
CRDT- 2017/04/20 06:00
AID - 10.1080/15563650.2017.1290253 [doi]
PST - ppublish
SO  - Clin Toxicol (Phila). 2017 Jun;55(5):346-351. doi: 10.1080/15563650.2017.1290253.
      Epub 2017 Feb 15.

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