PMID- 36034775
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220830
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - N-Acetylcysteine for Preventing Acetaminophen-Induced Liver Injury: A 
      Comprehensive Review.
PG  - 828565
LID - 10.3389/fphar.2022.828565 [doi]
LID - 828565
AB  - Aims: N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) 
      overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective 
      was to systematically review evidence of the use of NAC as a therapeutic option 
      for APAP overdose and APAP-related DILI in order to define the optimal treatment 
      schedule and timing to start treatment. Methods: Bibliographic databases (PubMed, 
      Web of Science, Embase, and MEDLINE) were searched for retrospective and 
      prospective cohort studies, case series, and clinical trials. The prespecified 
      primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events 
      (AEs). Results: In total, 34 studies of NAC usage in APAP-related DILI cases with 
      19,580 patients were identified, of which 2,376 patients developed 
      hepatotoxicities. The mortality rate across different studies ranged from 0 to 
      52%. Large variability of NAC regimens was found, i.e., intravenous (I.V.) 
      (100-150 mg/kg) and oral (70-140 mg/kg), and length of treatment varied-12, 24, 
      or 48 h for I.V. regimen and 72 h for oral administration. The timing of 
      initiation of NAC treatment showed different results in terms of occurrence of 
      hepatotoxicity and mortality; if started within 8 h and no more than 24 h from 
      APAP overdose, either intravenously or orally, NAC administration was efficacious 
      in terms of mortality. The most frequent AEs reported were anaphylactic 
      reactions, followed by cutaneous AEs for the IV route and intestinal AEs for the 
      oral one. Conclusion: NAC improves hepatotoxicity and reduces mortality. Timing 
      of treatment, ranging from 8 to 24 h from APAP overdose, regardless of the 
      regimen or route of administration, is important to prevent or minimize liver 
      damage, particularly in children and in elderly and obese patients.
CI  - Copyright (c) 2022 Licata, Minissale, Stankeviciute, Sanabria-Cabrera, Lucena, 
      Andrade and Almasio.
FAU - Licata, Anna
AU  - Licata A
AD  - Medicina Interna ed Epatologia, Dipartimento di Promozione della Salute, 
      Materno-infantile, di Medicina Interna e Specialistica di Eccellenza "G. 
      D'Alessandro," PROMISE, Universita degli Studi di Palermo, Palermo, Italy.
FAU - Minissale, Maria Giovanna
AU  - Minissale MG
AD  - Medicina Interna ed Epatologia, Dipartimento di Promozione della Salute, 
      Materno-infantile, di Medicina Interna e Specialistica di Eccellenza "G. 
      D'Alessandro," PROMISE, Universita degli Studi di Palermo, Palermo, Italy.
FAU - Stankeviciute, Simona
AU  - Stankeviciute S
AD  - Medicina Interna ed Epatologia, Dipartimento di Promozione della Salute, 
      Materno-infantile, di Medicina Interna e Specialistica di Eccellenza "G. 
      D'Alessandro," PROMISE, Universita degli Studi di Palermo, Palermo, Italy.
FAU - Sanabria-Cabrera, Judith
AU  - Sanabria-Cabrera J
AD  - UCICEC IBIMA, Plataforma SCReN (Spanish Clinical Research Network), Malaga, 
      Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, 
      CIBERehd, Madrid, Spain.
FAU - Lucena, Maria Isabel
AU  - Lucena MI
AD  - UCICEC IBIMA, Plataforma SCReN (Spanish Clinical Research Network), Malaga, 
      Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, 
      CIBERehd, Madrid, Spain.
AD  - Servicio de Aparato Digestivo, Instituto de Investigacion Biomedica de 
      Malaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de 
      Malaga, Malaga, Spain.
FAU - Andrade, Raul J
AU  - Andrade RJ
AD  - Servicio de Aparato Digestivo, Instituto de Investigacion Biomedica de 
      Malaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de 
      Malaga, Malaga, Spain.
AD  - Servicio de Aparato Digestivo, Instituto de Investigacion Biomedica de 
      Malaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de 
      Malaga, Malaga, Spain.
FAU - Almasio, Piero Luigi
AU  - Almasio PL
AD  - Medicina Interna ed Epatologia, Dipartimento di Promozione della Salute, 
      Materno-infantile, di Medicina Interna e Specialistica di Eccellenza "G. 
      D'Alessandro," PROMISE, Universita degli Studi di Palermo, Palermo, Italy.
LA  - eng
PT  - Systematic Review
DEP - 20220810
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9399785
OTO - NOTNLM
OT  - N-acetyl-cysteine
OT  - acetaminophen
OT  - drug-induced liver injury
OT  - hepatotoxicity
OT  - safety
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/30 06:00
MHDA- 2022/08/30 06:01
PMCR- 2022/08/10
CRDT- 2022/08/29 05:14
PHST- 2021/12/03 00:00 [received]
PHST- 2022/06/03 00:00 [accepted]
PHST- 2022/08/29 05:14 [entrez]
PHST- 2022/08/30 06:00 [pubmed]
PHST- 2022/08/30 06:01 [medline]
PHST- 2022/08/10 00:00 [pmc-release]
AID - 828565 [pii]
AID - 10.3389/fphar.2022.828565 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Aug 10;13:828565. doi: 10.3389/fphar.2022.828565. 
      eCollection 2022.