Comprehensive Bile Acid Profiling of ABCB4-mutated Patients and the Prognostic Role of Taurine-conjugated 3α,6α,7α,12α-Tetrahydroxylated Bile Acid in Cholestasis.

Background And Aims: 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.

Methods: 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.

Results: 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.

Conclusions: Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gamma-glutamyl transferase intrahepatic cholestasis patients.