Comprehensive Bile Acid Profiling of ABCB4-mutated Patients and the Prognostic Role of Taurine-conjugated  

作　　者：Teng Liu Ren-Xue Wang Jun Han Zhong-Die Li Jonathan ASheps Li-Juan Zheng Xiao-Xiao Xu Victor Ling Jian-She Wang 

机构地区：[1]Department of Pediatrics,Shanghai Medical College,Fudan University,The Center for Pediatric Liver Diseases,Children’s Hospital of Fudan University,Shanghai,China [2]BC Cancer Agency,Vancouver,British Columbia V5Z 1L3,Canada [3]University of Victoria-Genome BC Proteomics Center,University of Victoria,Victoria,British Columbia V8Z 7X8,Canada [4]Shanghai Key Laboratory of Birth Defect,Shanghai,China

出　　处：《Journal of Clinical and Translational Hepatology》2024年第2期151-161,共11页临床与转化肝病杂志（英文版）

基　　金：funded by the National Key Research and Development Program of China(Grant No.2021YFC 2700800)(to JSW);the National Natural Science Foundation of China,Grants No.82201898(to TL),82171853(to JSW).;supported by the Shanghai Sailing Program(20YF1402900 to TL);Health Industry Clinical Research Project of Shanghai Municipal Health Commission(20224Y0281 to TL);Chan-Xue-Yan Program of Fudan University(FDEKCXY17 to TL);the Canadian Institutes of Health Research(to VL&RW).

摘　　要：Background and Aims:We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid(tauro-THBA)in cholestasis.Methods:Serum bile acid profiles were evaluated in 13 ABCB4-mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry(UPLC/MRM-MS).The concentration of tauro-THBA was compared between ABCB4-mutated patients with different prognoses.The areas under the curve(AUCs)of tauro-THBA were compared between ABCB11-mutated patients with native liver survival and those who died or underwent liver transplantation before 3 years of age by receiver operating characteristic curve(ROC),with another patient cohort for further verification.Results:The overall hydrophobicity indices of bile acids in ABCB4-mutated patients(12.99±3.25 m)were significantly lower than those of healthy controls(14.02±1.74 m,p<0.000).That was due to markedly increased bile acid modifications including conjugation,sulfation,and ketonization.Differences in the tauro-THBA concentration in ABCB4-mutated patients with different prognoses were not significant.ROC analysis indicated that levels of tauro-THBA of<60 nM yielded an AUC of 0.900 with a sensitivity of 80%and specificity of 87.5%for ABCB11-mutated patients with different prognoses(p=0.0192).Of the 15 patients with good prognosis,14 were classified correctly and four of the five patients with a poor prognosis were classified correctly(14:15 vs.1:5,p=0.005)with tauro-THBA as a classifier.Conclusions:Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gammaglutamyl transferase intrahepatic cholestasis patients.

关 键 词：Bile acids MDR3 BSEP PFIC Liquid chromatography-mass spectrometry 

分 类 号：R575[医药卫生—消化系统]