regimen and 72 h for oral administration. 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. The mortality rate across different studies ranged from 0 to 52%. 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 prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs). Methods: Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. 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.
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