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Published on: September 20, 2019
A Japanese prospective multicenter study of urinary oxysterols in biliary atresia
Ken-Ichiro Konishi1,2, Tatsuki Mizuochi3, Hajime Takei4
1Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 8300011, Japan.
Insights
Urinary oxysterols, particularly 27-hydroxycholesterol, show promise as a diagnostic marker for biliary atresia (BA) in infants. This study suggests 27-hydroxycholesterol can help differentiate BA from other causes of neonatal cholestasis.
Area of Science:
- Biochemistry
- Pediatric Gastroenterology
- Diagnostic Biomarkers
Background:
- Biliary atresia (BA) diagnosis can be challenging, necessitating improved diagnostic tools.
- Neonatal cholestasis requires timely and accurate differentiation between BA and other conditions.
Purpose of the Study:
- To investigate the potential of urinary oxysterols as diagnostic markers for biliary atresia (BA) in Japanese children.
- To evaluate the efficacy of 27-hydroxycholesterol in distinguishing BA from non-BA cholestasis.
Main Methods:
- Prospective multicenter study involving infants under 6 months with cholestasis and healthy controls.
- Quantitative analysis of 7 urinary oxysterols using liquid chromatography/electrospray ionization-tandem mass spectrometry.
- Receiver operating characteristic (ROC) curve analysis to assess diagnostic performance.
Main Results:
- Total urinary oxysterols were significantly elevated in both BA and non-BA cholestasis groups compared to healthy controls.
- Urinary 27-hydroxycholesterol levels were significantly higher in BA patients than in non-BA cholestatic patients.
- ROC analysis indicated an area under the curve of 0.83 for 27-hydroxycholesterol in distinguishing BA from non-BA.
Conclusions:
- Urinary 27-hydroxycholesterol may serve as a valuable biomarker for differentiating biliary atresia from other causes of neonatal cholestasis.
- This study is the first to report on urinary oxysterol analysis in BA patients, highlighting a potential new diagnostic approach.
Abstract:
Diagnosis of biliary atresia (BA) can involve uncertainties. 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 months 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 4β-, 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 days; range 26-170) and 10 non-BA cholestatic controls (59; 14-162), as well as 10 HC (57; 25-120). Total urinary oxysterols were significantly greater in BA (median, 153.0 μmol/mol creatinine; range 24.1-486.7; P < 0.001) and non-BA (36.2; 5.8-411.3; P < 0.05) than in HC (2.7; 0.8-7.6). In patients with BA, urinary 27-hydroxycholesterol (3.61; 0.42-11.09; P < 0.01) was significantly greater than in non-BA (0.71; 0-5.62). 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. In conclusion, this first report of urinary oxysterol analysis in patients with BA indicated that 27-hydroxycholesterol may be a useful marker for distinguishing BA from other causes of neonatal cholestasis.

