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

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