文献类型：期刊文献

英文题名：Decoding liver injury: Vitamin D3 metabolite fingerprints in cholestatic liver disease diagnosis

作者：Qiu, Lanlan[1,2,3];Zhang, Lin[2,3];Hua, Lei[2,3];Wu, Qiong[2,3];Cao, Xinghao[4];Du, Yiping[2,3];Wei, Bo[4];Wu, Ting[2,3]

机构：[1]Jiangsu Vocat Coll Med, Sch Pharm, Yancheng 224005, Peoples R China;[2]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Res Ctr Anal & Test, Shanghai 200237, Peoples R China;[4]Naval Med Univ, Changzheng Hosp, Dept Infect Dis, Shanghai 200003, Peoples R China

年份：2025

卷号：577

外文期刊名：CLINICA CHIMICA ACTA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001538391500001)】；

基金：This work was supported by the High-end Training Funding Project for Professional Leaders in Higher Vocational Colleges in Jiangsu Province (2023GRFX033) and Research Projects of the Jiangsu Provincial Health Commission's Medical Science (H2023066).

语种：英文

外文关键词：Vitamin D3; Metabolites; Cholestatic liver diseases; Liver injury

摘要：Background: Conventional indicators for diagnosing liver injury in cholestatic liver diseases (CLD) include a combination of biochemical, imaging, and clinical assessments, which are critically limited by non-specificity, delayed detection windows, and poor correlation with cholestasis-specific mechanisms, underscoring the need for novel biomarker-driven strategies. Emerging biomarkers (e.g., vitamin D metabolites) are being explored to improve early diagnosis and specificity in liver injury assessment. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for simultaneous quantification of 25-hydroxyvitamin D3 [25-(OH)-D3], 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3], 24,25-dihydroxyvitamin D3 [24,25-(OH)2-D3], and the vitamin D metabolite ratio (VMR), providing a robust framework for assessing both systemic vitamin D deficiency and cholestatic liver injury severity. To interrogate vitamin D3 metabolism dynamics in CLD progression, statistical analyses-one-way ANOVA, correlation analysis, receiver operating characteristic (ROC) curves, and heatmaps-were applied to evaluate associations between metabolic profiles and liver injury severity. Results: Stratified by the Child-Pugh scoring system, serum levels of 25-(OH)-D3, 1,25-(OH)2-D3, 24,25-(OH)2-D3, and VMR exhibited a progressive decline across cohorts-healthy controls (HC), moderate liver injury (MLI), and severe liver injury (SLI)-correlating inversely with advancing disease severity. Notably, 24,25-(OH)2-D3 demonstrated superior diagnostic accuracy for CLD, achieving an area under the curve (AUC) of 0.994. Robust correlations between 25-(OH)-D3 and 24,25-(OH)2-D3 were observed in all cohorts (HC, MLI, SLI), though the regression slopes progressively attenuated in MLI and SLI cohorts, indicating preserved but diminished metabolic flux from 25-(OH)-D3 to 24,25-(OH)2-D3 as liver injury worsened. This attenuation aligns with progressive functional impairment in vitamin D3 metabolism. Clinically, post-treatment profiling following one week of hospitalization revealed that 25-(OH)-D3 exhibited superior sensitivity in tracking therapeutic responses compared to conventional cholestatic liver disease (CLD) indicators, underscoring their utility as dynamic biomarkers. Conclusions: The metabolites, particularly 24,25-(OH)2-D3, demonstrated excellent diagnostic accuracy for liver injury in CLD, while 25-(OH)-D3 outperformed conventional indicators in monitoring therapeutic response during cholestasis management.