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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 27, 2025; 17(10): 109770
Published online Oct 27, 2025. doi: 10.4254/wjh.v17.i10.109770
Published online Oct 27, 2025. doi: 10.4254/wjh.v17.i10.109770
Clinical characteristics and genetic causes of unexplained pediatric liver disease
Yuan Chen, Bao-Qi Chen, Hai-Yan Liu, Wen-Xin Shi, Lu Guo, Li-Feng Sun, Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Zhi-Yi Wang, Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
Zhi-Yi Wang, Hisense Postdoctoral Research Station, Hisense Research and Development Center, Qingdao 266104, Shandong Province, China
Zhi-Yi Wang, Zhi Liu, School of Information Science and Engineering, Shandong University, Qingdao 266237, Shandong Province, China
Yu-Juan Qi, Department of Pediatrics, Liaocheng Second People's Hospital, Liaocheng 252600, Shandong Province, China
Co-first authors: Yuan Chen and Zhi-Yi Wang.
Co-corresponding authors: Zhi Liu and Li-Feng Sun.
Author contributions: Chen Y and Wang ZY designed the study, collected and analyzed data, and wrote the manuscript; Sun LF and Liu Z contributed equally in guiding the study and ensured the scientific rigor of the study as co-corresponding authors; Sun LF is designated as the primary corresponding author for journal communications; Chen BQ, Qi YJ, Liu HY, Shi WX and Guo L provided technical and academic support; all authors have read and approve the final manuscript. Chen Y and Wang ZY contributed equally to this work as co-first authors. This study was a team effort, and Sun LF and Liu Z both made substantial key contributions throughout the study, which is in line with the principle of dual corresponding authorship. Specifically, Sun LF, as the head of pediatric gastroenterology department in Shandong Provincial Hospital Affiliated to Shandong First Medical University, oversaw the overall clinical diagnosis and treatment decision-making for pediatric patients with liver disease supervised the standardized implementation of the study, and played an irreplaceable leading role in the clinical appropriateness of the study design, systematic collection of case data, and the interpretation of the clinical significance of the results of the study. As the postdoctoral supervisor of the first authors, Chen Y and Wang ZY, Liu Z provided key guidance in the statistical modeling of genetic data, in-depth analysis of bioinformatics, and standardization of academic expression in the manuscript which laid a solid foundation for the methodological rigor of the study and the quality of the results presented. It is worth emphasizing that the "medical engineering integration" model represented by the two professors has effectively greatly enhanced the effectiveness of the team’s integration in the translation of clinical problems and the innovation of technical methods, which is a core guarantee for the high-quality completion of this study. Based on the aforementioned substantial contributions of the two professors and the special characteristics of the collaborative model, Sun LF and Liu Z were designated as co-corresponding authors which not only can objectively and comprehensively reflect their respective core contributions to the study, but also aligns with the scientific principles and normative requirements for the attribution of scientific research outcomes, and provides a clear objective basis for academic dissemination of the traceability of research responsibilities of the research results traceability.
Supported by National Natural Science Foundation of China, No. 82400641; and Natural Science Foundation of Shandong Province, No. ZR2022QH076 and ZR2021MH381.
Institutional review board statement: This retrospective study was approved by the Institutional Review Board of Shandong Provincial Hospital (Approval SWYX: No. 2022-210, Date: 2022-05-12).
Informed consent statement: The requirement for informed consent was waived due to the retrospective nature of the study and the use of de-identified data.
Conflict-of-interest statement: All authors declare no conflict of interest.
Data sharing statement: All relevant data supporting the findings of this study are available from the corresponding author upon reasonable request. To protect the confidentiality and privacy of the participants, the raw individual-level clinical data are not publicly available. However, de-identified datasets used for the statistical analyses, along with study protocols and analysis codes, may be shared with qualified researchers for academic and non-commercial use, subject to a data sharing agreement and approval by the Institutional Review Board.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li-Feng Sun, Chief Physician, PhD, Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jing Wu Road, Jinan 250021, Shandong Province, China. lifengsun2008@163.com
Received: June 6, 2025
Revised: June 26, 2025
Accepted: September 29, 2025
Published online: October 27, 2025
Processing time: 145 Days and 4.5 Hours
Revised: June 26, 2025
Accepted: September 29, 2025
Published online: October 27, 2025
Processing time: 145 Days and 4.5 Hours
Core Tip
Core Tip: In recent years, the number of pediatric patients with unexplained liver disease has been increasing. Whole-exome sequencing (WES) technology has played a significant role in the diagnosis; however, related studies remain limited. We found that WES significantly increased the diagnosis rate of liver diseases of unknown cause in children, guided personalized treatment, and improved prognosis. The mutation spectra of genes such as ATP7B and JAG1 provide important references for the molecular diagnosis of inherited liver diseases in Chinese children. In the future, functional studies and multi-omics integration will be required to elucidate the pathogenic mechanisms of novel variants and to advance the application of precision medicine in the field of pediatric hepatology.