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

Drug Saf. 2022 Nov;45(11):1329-1348. doi: 10.1007/s40264-022-01224-w. Epub 2022 Aug 25.

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.

Publication types

  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / adverse effects
  • Acetylcysteine / therapeutic use
  • Adolescent
  • Adrenal Cortex Hormones / adverse effects
  • Adult
  • Carnitine / adverse effects
  • Chemical and Drug Induced Liver Injury* / epidemiology
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / therapy
  • Child
  • Drug-Related Side Effects and Adverse Reactions*
  • Glutathione / adverse effects
  • Glycyrrhizic Acid / adverse effects
  • Humans
  • Infant, Newborn
  • Liver
  • Liver Failure, Acute* / drug therapy
  • Liver Failure, Acute* / therapy
  • Retrospective Studies
  • S-Adenosylmethionine / adverse effects
  • Ursodeoxycholic Acid / adverse effects

Substances

  • Adrenal Cortex Hormones
  • Acetaminophen
  • Glycyrrhizic Acid
  • Ursodeoxycholic Acid
  • S-Adenosylmethionine
  • Glutathione
  • Carnitine
  • Acetylcysteine