Therapeutic management of idiosyncratic drug‑induced liver injury and acetaminophen hepatotoxicity in the paediatric population: a systematic review.

Abstract

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 aim to comprehensively review the available literature on the therapies for both acetaminophen overdoses (APAP) and idiosyncratic DILI in the paediatric population.

Methods: We included original articles conducted in 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 retrieved, 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. 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 which have received specific treatment. These interventions appear to be mainly extrapolated from low-quality evidence from the adult population. Thus, there is a need of 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.