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Approaches for pediatric developmental drug-induced liver injury
Salminen, W. F., & Yang, X. (2015). Approaches for pediatric developmental drug-induced liver injury. In D. R. Mattison (Ed.), Computational Methods for Reproductive and Developmental Toxicology (pp. 255-287). CRC Press. https://doi.org/10.1201/b19189
Children are not simply small adults and it follows that children may exhibit differential sensitivity to drug-induced adverse events. This also applies to drug-induced liver injury (DILI). As an embryo develops, leading to the birth of a child, and eventually maturation into an adult, the human body goes through many different developmental phases. Various factors may make the developing human more or less susceptible to DILI when compared to adults. Drug-induced hepatotoxicity in children is commonly presented as acute hepatitis, although almost any major clinical pathological pattern of liver disease can occur. In most cases, children spontaneously recover after the offending medication is discontinued. The differential DILI responses observed between children and adults can be partly explained by the developmental changes of absorption, distribution, metabolism, and excretion. This article reviews the major developmental phases of the maturing liver with an emphasis on phases that may pose unique sensitivities to DILI. A review of the pediatric DILI literature is then presented so that pediatricians can better understand the potential hepatotoxicity risks associated with some drugs, such as antituberculous and antiepileptic medications.