Publication Name	World Journal of Hepatology
Manuscript ID	115037
Country	United States

Category	Gastroenterology & Hepatology
Manuscript Type	Editorial
Article Title	Whole-exome sequencing illuminates unexplained pediatric cholestatic liver disease
Manuscript Source	Invited Manuscript
All Author List	Toshifumi Yodoshi
Funding Agency and Grant Number
Corresponding Author	Toshifumi Yodoshi, MD, PhD, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, United States. toshifumi.yodoshi@cchmc.org
Key Words	Pediatric cholestasis; Genetic diagnosis; Whole exome sequencing; Precision medicine; Alagille syndrome; Wilson disease; Inherited metabolic liver disease
Core Tip	The advent of whole-exome sequencing (WES) has transformed diagnosis of unexplained pediatric liver disease. In infants with cholestasis and children with cryptogenic hepatitis, comprehensive genomic testing markedly increases diagnostic yield, often exceeding 50% in recent cohorts, enabling earlier identification and management. Incorporating WES early can spare patients invasive procedures, including diagnostic liver biopsy, and facilitate timely, targeted interventions. Yet, given phenotypic heterogeneity, WES must be integrated with careful clinical assessment, family history, and selective traditional diagnostics. Falling costs and faster turnaround make WES a practical cornerstone of precision hepatology, while validation and multi-omics remain essential to realize its full potential.
Citation	Yodoshi T. Whole-exome sequencing illuminates unexplained pediatric cholestatic liver disease. World J Hepatol 2025; In press

Received	2025-10-09 02:30
Peer-Review Started	2025-10-09 02:30
To Make the First Decision
Return for Revision	2025-10-21 07:30
Revised	2025-10-21 18:12
Second Decision	2025-11-24 02:45
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-11-24 07:47
Articles in Press	2025-11-24 07:47
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-5182 (online)
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