The association between N-acetylcysteine treatment and hepatic healing in patients with non-acetaminophen-induced liver injury in pediatric intensive care: A single-center retrospective study

Karaarslan, Utku; Çolak, Mustafa; Topal, Sevgi; Atakul, Gülhan; Soydan, Ekin; Çağlar, Aykut; Ağın, Hasan

doi:10.1016/j.arcped.2021.11.006

Cited by 2 publications

(8 citation statements)

References 24 publications

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“…Fifteen case reports, six case series, and four retrospective cohort studies, published between 1984 and 2022, with a total of 140 patients, from preterm newborn neonates to adolescents, were included (Table 1) . Most of the studies were conducted in infants (n = 6) [20][21][22][23][24][25][26] and children (n = 13) [27][28][29][30][31][32][33][34][35][36][37][38][39]. In addition, one study reported findings from either preterm newborn neonates [18] or term or postterm neonates [19], and four studies included adolescents [36,38,40,41] (of note, Novelli et al [36] and Scheffner et al [38] reported findings from both children and adolescents).…”

Section: Literature Search and Study Characteristicsmentioning

confidence: 99%

“…Therapeutical approaches used to manage DILI and DILI-related ALF were NAC (12 studies), ursodeoxycholic acid (UDCA) (three studies), corticosteroids (three studies), molecular adsorbent recirculating system (MARS) (three studies), continuous renal replacement therapy (CRRT, two studies), carnitine (one study), and the combination of glycyrrhizin, reduced glutathione (GSH), polyene phosphatidylcholine (PPC) and S-adenosylmethionine (one study). Ten studies provided heterogeneous DILI definitions [25,27,28,[34][35][36][37][38][39]42]. Two studies [34,35] adhered to the criteria set by the RegiSCAR group [43].…”

Section: Literature Search and Study Characteristicsmentioning

confidence: 99%

“…Two studies [34,35] adhered to the criteria set by the RegiSCAR group [43]. Karaarslan et al [25] defined liver injury as an elevation of transaminases six times the upper limit of normal (ULN). Rumack [27] defined hepatotoxicity due to APAP as aspartate aminotransferase (AST) levels > 1,000 IU/L.…”

Section: Literature Search and Study Characteristicsmentioning

confidence: 99%

“…The use of NAC for the treatment of APAP was reported in 13 infants [20][21][22][23][24][25]. In six of them, parental or medical inadvertent overdosage of acetaminophen was the cause of DILI, while the remaining seven received NAC for idiosyncratic DILI.…”

Section: N-acetylcysteinementioning

confidence: 99%

“…Infants presented with severe liver damage (n = 2) or ALF (n = 1). The vast majority (n = 12) recovered spontaneously after the administration of oral or intravenous NAC (initial doses ranging from 5 mg/kg/h to 1,000 mg) [20,[22][23][24][25]. The one infant who died was misdiagnosed with acute encephalopathy and received supportive treatment.…”

Section: N-acetylcysteinementioning

confidence: 99%

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Therapeutic Management of Idiosyncratic Drug-Induced Liver Injury and Acetaminophen Hepatotoxicity in the Paediatric Population: A Systematic Review

et al. 2022

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Introduction Drug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is scarce. Objective We aimed to comprehensively review the available literature on the therapies for both acetaminophen overdose (APAP) and idiosyncratic DILI in the paediatric population. Methods We included original articles conducted in a paediatric population (< 18 years) in which a therapeutic intervention was described to manage APAP or idiosyncratic DILI. Findings were summarized based on age groups (preterm newborn neonates, term and post-term neonates, infants, children and adolescents). Results Overall, 25 publications (fifteen case reports, six case series and four retrospective cohort studies) were included, including a total of 140 paediatric DILI cases, from preterm newborn neonates to adolescents. N-acetylcysteine was used to treat 19 APAP cases. N-acetylcysteine (n = 14), ursodeoxycholic acid (n = 3), corticosteroids (n = 31), carnitine (n = 16) and the combination of glycyrrhizin, reduced glutathione, polyene phosphatidylcholine and S-adenosylmethionine (n = 31) were the therapeutic options for treating idiosyncratic DILI. The molecular adsorbent recirculating system was used in the management of either APAP (n = 4) or idiosyncratic DILI (n = 2), while 20 paediatric ALF cases received continuous renal replacement therapy. Conclusions This systematic review identified DILI in the paediatric population who have received specific treatment. These interventions appear to be mainly extrapolated from low-quality evidence from the adult population. Thus, there is a need for high-quality studies to test the efficacy of known and novel therapies to treat DILI specifically addressed to the paediatric population. PROSPERO registration number CRD42021214702.

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Section: Literature Search and Study Characteristicsmentioning

confidence: 99%

Section: Literature Search and Study Characteristicsmentioning

confidence: 99%

Section: Literature Search and Study Characteristicsmentioning

confidence: 99%

Section: N-acetylcysteinementioning

confidence: 99%

Section: N-acetylcysteinementioning

confidence: 99%

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Therapeutic Management of Idiosyncratic Drug-Induced Liver Injury and Acetaminophen Hepatotoxicity in the Paediatric Population: A Systematic Review

et al. 2022

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Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective

Jerome,

Zahn,

Abner

et al. 2024

Transl Gastroenterol Hepatol

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Background The World Health Organization (WHO)’s Essential Medicines List (EML) plays an important role in advocating for access to key treatments for conditions affecting people in all geographic settings. We applied our established drug repurposing methods to one EML agent, N-acetylcysteine (NAC), to identify additional uses of relevance to the global health community beyond its existing EML indication (acetaminophen toxicity). Methods We undertook a phenome-wide association study (PheWAS) of a variant in the glutathione synthetase ( GSS ) gene in approximately 35,000 patients to explore novel indications for use of NAC, which targets glutathione. We then evaluated the evidence regarding biologic plausibility, efficacy, and safety of NAC use in the new phenotype candidates. Results PheWAS of GSS variant R418Q revealed increased risk of several phenotypes related to non-acetaminophen induced acute liver failure (ALF), indicating that NAC may represent a therapeutic option for treating this condition. Evidence review identified practice guidelines, systematic reviews, clinical trials, retrospective cohorts and case series, and case reports. This evidence suggesting benefit of NAC use in this subset of ALF patients. The safety profile of NAC in this literature was also concordant with existing evidence on safety of this agent in acetaminophen-induced ALF. Conclusions This body of literature indicates efficacy and safety of NAC in non-acetaminophen induced ALF. Given the presence of NAC on the EML, this medication is likely to be available across a range of resource settings; promulgating its use in this novel subset of ALF can provide healthcare professionals and patients with a valuable and safe complement to supportive care for this disease.

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The association between N-acetylcysteine treatment and hepatic healing in patients with non-acetaminophen-induced liver injury in pediatric intensive care: A single-center retrospective study

Cited by 2 publications

References 24 publications

Therapeutic Management of Idiosyncratic Drug-Induced Liver Injury and Acetaminophen Hepatotoxicity in the Paediatric Population: A Systematic Review

Therapeutic Management of Idiosyncratic Drug-Induced Liver Injury and Acetaminophen Hepatotoxicity in the Paediatric Population: A Systematic Review

Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective

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