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Serum 7-alpha-hydroxy-4-cholesten-3-one as a marker for bile acid loss in children
Folke Freudenberg1, Florian Gothe, Florian Beigel
1Department of Pediatric Gastroenterology and Hepatology, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
Insights
This study establishes normal 7-alpha-hydroxy-4-cholesten-3-one (C4) levels in children, finding elevated C4 in short bowel syndrome (SBS) patients indicates bile acid malabsorption.
Area of Science:
- Pediatric Gastroenterology
- Clinical Chemistry
- Biomarker Discovery
Background:
- Bile acid malabsorption is a significant complication in pediatric short bowel syndrome (SBS).
- Accurate assessment of bile acid malabsorption in children is crucial for effective management.
- 7-alpha-hydroxy-4-cholesten-3-one (C4) is a potential biomarker for bile acid synthesis and absorption.
Purpose of the Study:
- To determine age- and sex-independent reference values for serum C4 in a healthy pediatric population.
- To evaluate the utility of serum C4 levels in diagnosing bile acid malabsorption in children with SBS.
Main Methods:
- Serum C4 concentrations were measured using high-performance liquid chromatography in 100 healthy children and 12 pediatric SBS patients.
- Reference values were established based on a log-normal distribution, defining the upper limit of normal.
- Fasting serum samples were collected between 8:00 a.m. and 11:00 a.m. after a 10-hour fast.
Main Results:
- The upper limit of normal for serum C4 in healthy children was determined to be 66.5 ng/mL, with no significant age or sex correlation.
- 97% of healthy children had C4 levels below this established upper limit.
- All 12 SBS patients exhibited significantly elevated C4 concentrations (mean 299.6 ± 167.8 ng/mL), indicating bile acid malabsorption.
Conclusions:
- Established pediatric reference values for C4 are consistent with adult levels and are independent of age and sex.
- Elevated serum C4 concentrations reliably identify bile acid malabsorption in pediatric SBS patients.
- Serum C4 offers a noninvasive, nonisotopic method for assessing bile acid malabsorption in children.
Objective:
To establish age-related reference values for 7-alpha-hydroxy-4-cholesten-3-one (C4) in a pediatric population and to investigate bile acid malabsorption in children with short bowel syndrome (SBS).
Study Design:
Serum was obtained between 8:00 a.m. and 11:00 a.m. from 100 healthy children (52% males, 9 months to 18 years of age) after 10 hours of fasting. Pediatric patients with SBS served as disease controls (n = 12). Following solid-phase extraction and purification, C4 was determined by high-performance liquid chromatography using a ultraviolet detector at a wavelength of 241 nm. The upper limit of normal for C4 concentrations was defined as the mean plus 2 SD of the log-normal distribution.
Results:
The mean concentration and SD of C4 in healthy children was 22.8 ± 15.8 ng/mL with no relation to age or sex and an upper limit of normal of 66.5 ng/mL. Normal C4 values were found in 97 of 100 healthy children, and all 12 patients with SBS had C4 concentrations above 100 ng/mL (mean 299.6 ± 167.8 ng/mL; range 105.7-562.1 ng/mL, P < .0001 compared with controls).
Conclusions:
The determined upper limit of normal for C4 concentration in healthy children corresponds to previously published levels in healthy adults and is independent of age and sex. The consistently elevated C4 concentrations in our patients with SBS confirm the reliability of this noninvasive, nonisotopic method to assess bile acid malabsorption in children.
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