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Drug-induced liver injury in children
  1. Bharanikumar Ravikumar1,
  2. Guruprasad Aithal2,3,
  3. Chayarani Kelgeri4
  1. 1 Birmingham Women’s and Children’s Hospitals NHS Foundation Trust, Birmingham, Birmingham, UK
  2. 2 NIHR Nottingham Biomedical Research Centre, Nottingham, UK
  3. 3 Nottingham University Hospitals NHS Trust, Nottingham, UK
  4. 4 Paediatric Hepatology and Transplant Unit, Birmingham Women’s and Children’s Hospitals NHS Foundation Trust, Birmingham, UK
  1. Correspondence to Dr Chayarani Kelgeri, Paediatric Hepatology and Transplant Unit, Birmingham Women’s and Children’s Hospitals NHS Foundation Trust, Birmingham, Birmingham, UK; chayarani.kelgeri{at}

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Key points

  • Drug-induced liver injury should be suspected in every child with abnormal liver biochemistry.

  • Awareness of signature patterns of drug-induced liver injury aids diagnosis.

  • Revised Electronic Causality Assessment Method calculator with other tools may facilitate diagnosis.

  • Genetic testing has a role in causality assessment and risk management.

  • Suspected drug-induced liver injury should be reported by yellow card to Medicines and Health Care Products Regulatory Agency.


An adolescent boy presents to the emergency department after being unwell for 2 days with vomiting and abdominal pain. His clinical examination is normal except for scleral icterus. Blood tests reveal total serum bilirubin of 27 µmol/L, direct bilirubin of 21 µmol/L, alanine aminotransferase (ALT) 261 IU/L, aspartate aminotransferase 210 IU/L, alkaline phosphatase (ALP) 309 IU/L, gamma-glutamyl transferase 117 IU/L (reference range,1 table 1). His full blood count, urea, creatinine and international normalised ratio (INR) are in the normal range. Drug history includes atomoxetine for attention deficit hyperactivity disorder for a year and flucloxacillin 3 weeks back for finger cellulitis. Are drugs the cause of his liver injury and if so which drug?

View this table:
Table 1

Reference range for blood tests in children (RCPCH)1

Drug-induced liver injury (DILI, box 1)2 is an adverse drug reaction (ADR) to prescription medications, herbal and dietary supplements and xenobiotics. It is an under-recognised and under-reported cause of liver injury in children. DILI can range from an asymptomatic rise in liver transaminases to severe liver injury, leading to acute liver failure (ALF) and death without liver transplantation.3–5 It is more pronounced in children with chronic illnesses and polypharmacy. Diagnosis is challenging in the absence of definitive diagnostic tests and biomarkers. A thorough history with a high index of suspicion and excluding other liver pathologies is the cornerstone for diagnosis. Reviewing the summary of product characteristics and being aware of the inverted black triangle warning (▼) that …

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  • X @Chaya

  • Contributors BR did literature search, wrote the first draft, CK coordinated the writing of this draft, did literature search and edited the draft. GA provided expert advice and edited the draft. QuillBot for grammar check.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer-reviewed.