Yiğit H, Gökoğlu A, Gökoğlu S. Letter to the Editor: Causality dilemma of cytochrome P450 1A2 reduction in neonatal cholestasis. World J Clin Pediatr 2026; 15(3): 118192 [DOI: 10.5409/wjcp.118192]
Corresponding Author of This Article
Hüseyin Yiğit, PhD, Assistant Professor, Lecturer, Cappadocia Vocational School, Department of Medical Services and Techniques, Cappadocia University, Ahmet Taner Kışlalı Street, Hadosan, Ürgüp, Nevsehir 50400, Türkiye. anatomisth@gmail.com
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Pediatrics
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letter
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Yiğit H, Gökoğlu A, Gökoğlu S. Letter to the Editor: Causality dilemma of cytochrome P450 1A2 reduction in neonatal cholestasis. World J Clin Pediatr 2026; 15(3): 118192 [DOI: 10.5409/wjcp.118192]
World J Clin Pediatr. Sep 9, 2026; 15(3): 118192 Published online Sep 9, 2026. doi: 10.5409/wjcp.118192
Letter to the Editor: Causality dilemma of cytochrome P450 1A2 reduction in neonatal cholestasis
Hüseyin Yiğit, Abdulkerim Gökoğlu, Sonay Gökoğlu
Hüseyin Yiğit, Cappadocia Vocational School, Department of Medical Services and Techniques, Cappadocia University, Nevsehir 50400, Türkiye
Abdulkerim Gökoğlu, Department of Neurosurgery, Konya State Educating & Teaching Hospital, Konya 42020, Türkiye
Sonay Gökoğlu, Department of Pediatrics, Erciyes Kartal Hospital, Kayseri 38050, Türkiye
Author contributions: Yiğit H contributed to conceptualization, methodology, supervision, project administration; Gökoğlu A contributed to resources, investigation, literature search; Gökoğlu S contributed to formal analysis (clinical/neonatal perspective), validation, writing – review & editing; Yiğit H and Gökoğlu A contributed to writing – original draft.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
Corresponding author: Hüseyin Yiğit, PhD, Assistant Professor, Lecturer, Cappadocia Vocational School, Department of Medical Services and Techniques, Cappadocia University, Ahmet Taner Kışlalı Street, Hadosan, Ürgüp, Nevsehir 50400, Türkiye. anatomisth@gmail.com
Received: December 28, 2025 Revised: January 29, 2026 Accepted: February 26, 2026 Published online: September 9, 2026 Processing time: 217 Days and 3 Hours
Abstract
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.
Core Tip: This letter provides a critical perspective on the findings of Kotb et al regarding cytochrome P450 1A2 levels in neonatal cholestasis. We highlight the causality dilemma, suggesting that reduced enzyme levels may be a secondary consequence of inflammation and liver injury rather than an inherent “defect”. Furthermore, we address methodological concerns, including the lack of genetic validation and the limitations of using enzyme-linked immunosorbent assay to estimate functional metabolic capacity. We emphasize the need to explicitly differentiate between primary genetic defects and secondary downregulation induced by liver injury. We propose incorporating functional probe drug assays (e.g., caffeine clearance) and transcriptomic profiling to validate these phenotypic observations, ensuring safer pharmacological management.
