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 bi...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.展开更多
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).+3 种基金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).
文摘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.
