Comprehensive bile acid profiling in hereditary intrahepatic cholestasis: Genetic and clinical correlations

Teng Liu, Ren Xue Wang, Jun Han, Chen Zhi Hao, Yi Ling Qiu, Yan Yan Yan, Li Ting Li, Neng Li Wang, Jing Yu Gong, Yi Lu, Mei Hong Zhang, Xin Bao Xie, Jun Cong Yang, Yi Jie You, Jia qi Li, A. S. Knisely, Christoph H. Borchers, Victor Ling, Jian She Wang

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Background & Aims: Genetic defects causing dysfunction in bile salt export pump (BSEP/ABCB11) lead to liver diseases. ABCB11 mutations alter the bile acid metabolome. We asked whether profiling plasma bile acids could reveal compensatory mechanisms and track genetic and clinical status. Methods: We compared plasma bile acids in 17 ABCB11-mutated patients, 35 healthy controls and 12 genetically undiagnosed cholestasis patients by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS). We developed an index to rank bile acid hydrophobicity, and thus toxicity, based on LC retention times. We recruited 42 genetically diagnosed hereditary cholestasis patients, of whom 12 were presumed to have impaired BSEP function but carried mutations in genes other than ABCB11, and 8 healthy controls, for further verification. Results: The overall hydrophobicity indices of total bile acids in both the ABCB11-mutated group (11.89 ± 1.07 min) and the undiagnosed cholestasis group (11.46 ± 1.07 min) were lower than those of healthy controls (13.69 ± 0.77 min) (both p < 0.005). This was owing to increased bile acid modifications. Secondary bile acids were detected in patients without BSEP expression, suggesting biliary bile acid secretion through alternative routes. A diagnostic panel comprising lithocholic acid (LCA), tauro-LCA, glyco-LCA and hyocholic acid was identified that could differentiate the ABCB11-mutated cohort from healthy controls and undiagnosed cholestasis patients (AUC=0.946, p < 0.0001) and, in non-ABCB11-mutated cholestasis patients, could distinguish BSEP dysfunction from normal BSEP function (9/12 vs 0/38, p < 0.0000001). Conclusions: Profiling of plasma bile acids has provided insights into cholestasis alleviation and may be useful for the clinical management of cholestatic diseases.

Original languageEnglish
Pages (from-to)1676-1685
Number of pages10
JournalLiver International
Issue number9
Publication statusPublished - Sep 2018
Externally publishedYes


  • ABCB11
  • bile salt export pump
  • liquid chromatography-mass spectrometry
  • PFIC2


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