PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gamma-glutamyl transferase intrahepatic cholestasis patients.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gamma-glutamyl transferase intrahepatic cholestasis patients.
摘要：
■我们询问了全面的胆汁酸分析是否可以为ABCB4突变患者的病理生理学提供见解，并评估了牛磺酸缀合的四羟基化胆汁酸（tauro-THBA）在胆汁淤积中的预后价值。
■通过超高效液相色谱/多反应监测-质谱（UPLC/MRM-MS）评估了13例ABCB4突变患者和65例健康对照的血清胆汁酸谱。比较了不同预后的ABCB4突变患者的tauro-THBA浓度。通过受试者工作特征曲线（ROC）比较了具有天然肝脏存活率的ABCB11突变患者和在3岁之前死亡或接受肝移植的患者之间的tauro-THBA曲线下面积（AUC），与另一个患者队列进行进一步验证。
■ABCB4突变患者胆汁酸的总体疏水性指数（12.99±3.25m）明显低于健康对照组（14.02±1.74m，p<0.000)。这是由于显著增加的胆汁酸修饰，包括缀合，硫酸化，和酮化。不同预后的ABCB4突变患者的tauro-THBA浓度差异不显著。ROC分析表明，对于具有不同预后的ABCB11突变患者，<60nM的tauro-THBA水平产生0.900的AUC，灵敏度为80％，特异性为87.5％（p=0.0192）。在15例预后良好的患者中，14例正确分类，5例预后不良的患者中有4例正确分类（14：15vs.1：5，p=0.005），以tauro-THBA作为分类器。
■Tauro-THBA浓度可能是预测低γ-谷氨酰转移酶肝内胆汁淤积患者临床结果的生物标志物。
■通过超高效液相色谱/多反应监测-质谱（UPLC/MRM-MS）评估了13例ABCB4突变患者和65例健康对照的血清胆汁酸谱。比较了不同预后的ABCB4突变患者的tauro-THBA浓度。通过受试者工作特征曲线（ROC）比较了具有天然肝脏存活率的ABCB11突变患者和在3岁之前死亡或接受肝移植的患者之间的tauro-THBA曲线下面积（AUC），与另一个患者队列进行进一步验证。
■ABCB4突变患者胆汁酸的总体疏水性指数（12.99±3.25m）明显低于健康对照组（14.02±1.74m，p<0.000)。这是由于显著增加的胆汁酸修饰，包括缀合，硫酸化，和酮化。不同预后的ABCB4突变患者的tauro-THBA浓度差异不显著。ROC分析表明，对于具有不同预后的ABCB11突变患者，<60nM的tauro-THBA水平产生0.900的AUC，灵敏度为80％，特异性为87.5％（p=0.0192）。在15例预后良好的患者中，14例正确分类，5例预后不良的患者中有4例正确分类（14：15vs.1：5，p=0.005），以tauro-THBA作为分类器。
■Tauro-THBA浓度可能是预测低γ-谷氨酰转移酶肝内胆汁淤积患者临床结果的生物标志物。
