Liu Teng, Wang Ren-Xue, Han Jun, Li Zhong-Die, Sheps Jonathan A, Zheng Li-Juan, Xu Xiao-Xiao, Ling Victor, Wang Jian-She
Department of Pediatrics, Shanghai Medical College, Fudan University, The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China.
BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
J Clin Transl Hepatol. 2024 Feb 28;12(2):151-161. doi: 10.14218/JCTH.2023.00095. Epub 2023 Sep 15.
We asked if comprehensive bile acid profiling could provide insights into the physiopathology of -mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid (tauro-THBA) in cholestasis.
Serum bile acid profiles were evaluated in 13 -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 -mutated patients with different prognoses. The areas under the curve (AUCs) of tauro-THBA were compared between -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.
The overall hydrophobicity indices of bile acids in -mutated patients (12.99±3.25 m) were significantly lower than those of healthy controls (14.02±1.74 m, <0.000). That was due to markedly increased bile acid modifications including conjugation, sulfation, and ketonization. Differences in the tauro-THBA concentration in -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 -mutated patients with different prognoses (=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, =0.005) with tauro-THBA as a classifier.
Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gamma-glutamyl transferase intrahepatic cholestasis patients.
我们探讨了全面的胆汁酸谱分析能否为[具体基因]突变患者的生理病理学提供见解，并评估了牛磺酸结合四羟基胆汁酸（tauro-THBA）在胆汁淤积中的预后价值。
采用超高效液相色谱/多反应监测质谱法（UPLC/MRM-MS）对13例[具体基因]突变患者和65名健康对照者的血清胆汁酸谱进行评估。比较不同预后的[具体基因]突变患者中tauro-THBA的浓度。通过受试者工作特征曲线（ROC）比较[具体基因]突变患者中自然肝存活者与3岁前死亡或接受肝移植者的tauro-THBA曲线下面积（AUC），并使用另一组患者进行进一步验证。
[具体基因]突变患者胆汁酸的总体疏水性指数（12.99±3.25 m）显著低于健康对照者（14.02±1.74 m，P<0.000）。这是由于胆汁酸修饰（包括结合、硫酸化和酮化）明显增加所致。不同预后的[具体基因]突变患者中tauro-THBA浓度差异无统计学意义。ROC分析表明，对于不同预后的[具体基因]突变患者，tauro-THBA水平<60 nM时，AUC为0.900，敏感性为80%，特异性为87.5%（P=0.0192）。以tauro-THBA作为分类指标，15例预后良好的患者中有14例分类正确，5例预后不良的患者中有4例分类正确（14:15 vs. 1:5，P=0.005）。
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局的生物标志物。
