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In the present prospective multicenter study, we considered whether urinary oxysterols represent a useful marker for diagnosis of BA in Japanese children. Subjects under 6\u00a0months old at 7 pediatric centers in Japan were prospectively enrolled, including patients with cholestasis and healthy controls (HC) without liver disease. Patients with cholestasis constituted 2 groups representing BA patients and others with cholestasis from other causes (non-BA). We quantitatively analyzed 7 oxysterols including 4\u03b2-, 20(S)-, 22(S)-, 22(R)-, 24(S)-, 25-, and 27-hydroxycholesterol by liquid chromatography\/electrospray ionization-tandem mass spectrometry. Enrolled subjects included 14 with BA (median age 68\u00a0days; range 26\u2013170) and 10 non-BA cholestatic controls (59; 14\u2013162), as well as 10 HC (57; 25\u2013120). Total urinary oxysterols were significantly greater in BA (median, 153.0\u00a0\u03bcmol\/mol creatinine; range 24.1\u2013486.7; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and non-BA (36.2; 5.8\u2013411.3; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) than in HC (2.7; 0.8\u20137.6). In patients with BA, urinary 27-hydroxycholesterol (3.61; 0.42\u201311.09; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) was significantly greater than in non-BA (0.71; 0\u20135.62). In receiver operating characteristic (ROC) curve analysis for distinguishing BA from non-BA, the area under the ROC curve for urinary 27-hydroxycholesterol was 0.83. 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