Document resource
The Metabolic Biochemistry Network (MetBioNet) comprises 18 inherited metabolic disease (IMD) laboratories in the UK and Ireland, most based in tertiary paediatric centres. In 2021, MetBioNet stakeholders noted a marked increase in metabolic test requests for children with fatty liver disease, particularly free fatty acids (FFA), despite unclear diagnostic value. This increase appeared temporally associated with the publication of the 2020 British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) fatty liver guideline, 1 which recommends a broad panel of metabolic tests, including FFA, as first-line investigations in all patients.A literature review was conducted to evaluate the evidence supporting metabolic testing, including FFA measurement, in the investigation of paediatric fatty liver. Four regional metabolic centres reviewed 12 months of metabolic requests for fatty liver investigations, assessing workload, financial cost, and diagnostic yield. Paediatric hepatologists were consulted regarding local adherence to the BSPGHAN guideline and its perceived appropriateness.Published literature highlights the importance of identifying treatable causes of fatty liver, including IMDs, hence the recommendations for metabolic testing2 and advises a stepwise diagnostic approach: metabolic testing is appropriate as first-line in children under 3 years of age, but should be reserved as second-line in older patients when clinically indicated and, in children over 10 years, only following a trial of other interventions. No evidence supporting a role for FFA in the investigation of fatty liver was identified. Across the four centres, the most frequently requested tests in patients over 10 years of age were plasma amino acids, urine organic acids, bloodspot or plasma acylcarnitines and FFA; very long-chain fatty acids were also commonly requested, likely due to confusion with FFA. When extrapolated nationally, the estimated annual cost of IMD investigations in older children with fatty liver was £152,000, equivalent to approximately £700,000 since MetBioNet first raised concerns in 2021. No IMDs were diagnosed during the review period. The review also highlighted that a number of patients were re-bled for further investigations due to mildly abnormal results, which were attributed to dietary influences. Discussions with local hepatologists revealed variable practice: while some centres excluded FFA or deferred metabolic investigations, others adhered closely to the guideline despite recognising its limited utility.The BSPGHAN fatty liver guideline is widely implemented across the UK, however, current evidence does not support routine first-line metabolic testing in all patients. Inclusion of FFA appears erroneous. Adopting an age-stratified, stepwise approach would reduce unnecessary testing, financial burden, and laboratory workload associated with the guideline. Specialist input from metabolic experts (Clinicians and Laboratory Scientists) should be incorporated into future guideline revisions, with mechanisms for timely updates when evidence or expert consensus identifies areas for improvement.References British Society of Paediatric Gastroenterology Hepatology and Nutrition UK Fatty Liver Guideline (2020). https://bspghan.org.uk/wp-content/uploads/2020/08/LSG_UK-Fatty-Liver-Guideline-August-2020.pdfVajro P, Lenta S, Socha P, et al. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN hepatology committee. JPGN 2012;54:700–713.