Letter to the Editor: Causality dilemma of cytochrome P450 1A2 reduction in neonatal cholestasis.

This letter discusses the pilot study by Kotb et al published in World Journal of Clinical Pediatrics, which identifies significantly reduced serum cytochrome P450 1A2 (CYP1A2) levels in neonates with biliary atresia and neonatal hepatitis compared to healthy controls. While these findings highlight a potential role for detoxification mechanisms in neonatal cholestasis, critical methodological issues regarding the interpretation of results warrant attention. The primary concern is the causality dilemma; it is crucial to distinguish between an innate 'defect' (congenital deficiency) and 'downregulation' (secondary suppression). Low CYP1A2 levels may be a secondary consequence of systemic inflammation rather than an inherent susceptibility factor. Furthermore, the reliance on enzyme-linked immunosorbent assay for protein abundance lacks the resolution of functional activity assays. Future research should integrate single-cell multi-omics and gut-metabolite signaling to decode the complexity of the hepatic microenvironment.