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 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.

Fig. 1

Flow chart of the literature review process

Fig. 2

Therapeutical options for the management of idiosyncratic drug-induced liver injury and acetaminophen hepatotoxicity in paediatric patients. ALF acute liver failure, CVVH continuous venovenous hemofiltration, GSH reduced glutathione, LTx liver transplantation, MARS molecular adsorbent recirculating system, NA not available, NAC N-acetylcysteine, PPC polyene phosphatidylcholine, SAM S-adenosylmethionine, TMP-SMZ sulfamethoxazole-trimethoprim, UDCA ursodeoxycholic acid

Fig. 3

Quality assessment of included case reports, case series and retrospective cohort studies