Differential Diagnosis of Acute Liver Failure in Children: A Systematic Review

PURPOSE: To develop a probability-based differential diagnosis for pediatric acute liver failure (PALF) based on age and socioeconomic status of the country of origin. METHODS: Comprehensive literature search using PubMed, EMBASE, and SCOPUS databases was performed. Children 0–22 years of age who met PALF registry criteria were included. Articles included >10 children, and could not be a case report, review article, or editorial. No language filter was utilized, but an English abstract was required. Etiology of PALF, age of child, and country of origin was extracted from included articles. RESULTS: 32 full text articles were reviewed in detail; 2,982 children were included. The top diagnosis of PALF in developed countries was acetaminophen toxicity (9.24%; 95% CredI 7.99–10.6), whereas in developing countries it was Hepatitis A (28.9%; 95% CredI 26.3–31.7). In developed countries, the leading diagnosis of PALF in children aged <1 year was metabolic disorder (17.2%; 95% CredI 10.3–25.5), whereas in developing countries it was unspecified infection (39.3%; CredI 27.6–51.8). In developed countries, the leading diagnosis in children aged >1 year was Non-A-B-C Hepatitis (8.18%; CredI 5.28–11.7), whereas in developing countries it was Hepatitis A (32.4%; CredI 28.6–36.3). CONCLUSION: The leading causes of PALF in children aged 0-22 years differ depending on the age and developmental status of their country of origin, suggesting that these factors must be considered in the evaluation of children with PALF.