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Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1 . Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed.AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells.Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins.HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

A 13-year-old girl presented to the emergency department with acute onset of chest pain, nausea and tremor. The patient denied drug ingestion, and urine toxicology was negative. ECG demonstrated sinus tachycardia, prolonged QTc (541 ms) and ST depression. Laboratory testing demonstrated metabolic acidosis, hypokalaemia, hypophosphataemia and hyperglycaemia. She was commenced on continuous cardiac monitoring and treated with intravenous fluids and electrolyte replacement. Presenting features and laboratory abnormalities resolved within 48 hours. The National Poisons Information Service and Clinical Biochemistry were integral to her management, advising the clinical team on the likeliest aetiology. Five weeks after discharge, urine toxicology, using mass spectrometry, identified clenbuterol. Clenbuterol is an oral β2-agonist with anabolic and lipolytic effects that is misused as a performance and image enhancing drug. Clinicians must be aware of the increasing availability of these drugs and their potential for causing harm in children and adolescents.

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Sudden-onset disseminated intravascular coagulation (DIC) occurred 3 h after uneventful polymethacrylate bone cement insertion for a revision left Charnley hip replacement. Profuse bleeding caused a hypovolaemic state aggravating existing myocardial ischaemia; as a result death occurred secondary to myocardial infarction 6 h after operation.