Therapeutic Management of Idiosyncratic Drug-Induced Liver Injury and Acetaminophen Hepatotoxicity in the Paediatric Population: A Systematic Review
What this study found
Overall, most paediatric patients recovered after treatment, but the evidence was very low quality and too heterogeneous to support firm efficacy conclusions. N-acetylcysteine was the main treatment for acetaminophen overdose in children, and all reported APAP cases treated with NAC recovered, although one infant death was possibly related to delayed administration. For idiosyncratic DILI, outcomes were more variable: UDCA was associated with 2 liver transplants and 1 recovery across 3 cases, corticosteroids were used in 31 cases with multiple recoveries, and the glycyrrhizin/reduced…
- Study & population
- Systematic review of paediatric patients under 18 years with drug-induced liver injury or acetaminophen hepatotoxicity, including neonates, infants, children, and adolescents.
- Intervention
- This systematic review summarized paediatric treatments for acetaminophen hepatotoxicity and idiosyncratic drug-induced liver injury, including N-acetylcysteine, ursodeoxycholic acid, corticosteroids, carnitine, and a combination of glycyrrhizin, reduced glutathione, polyene phosphatidylcholine, and…
- Key limitation
- The review was based mainly on case reports and case series, with very small treatment groups and major clinical heterogeneity across etiologies, ages, and dosing regimens.
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Open PDFOriginal abstract
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. We aimed to comprehensively review the available literature on the therapies for both acetaminophen overdose (APAP) and idiosyncratic DILI in the paediatric population. 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). 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. 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.