Bile acid malabsorption assessed by 7 alpha-hydroxy-4-cholesten-3-one in pediatric inflammatory bowel disease: correlation to clinical and laboratory findings

J Crohns Colitis. 2014 Sep;8(9):1072-8. doi: 10.1016/j.crohns.2014.02.027. Epub 2014 Mar 22.

Abstract

Background and aims: Measurement of 7 alpha-hydroxy-4-cholesten-3-one (C4) in serum is a semiquantitative test for bile acid malabsorption (BAM). We have previously established pediatric normal values for C4 with an upper limit of normal of 66.5 ng/mL, independent of age and sex. Here we performed the C4 test in 58 pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC).

Methods: C4 was measured using high performance liquid chromatography (HPLC) in fasting serum samples of 44 patients with CD (range 7-19 years) and 14 with UC (4-18 years). Disease activity was assessed by the pediatric CD and UC activity indices (PCDAI and PUCAI, respectively) plus serum (CRP, ESR) and fecal inflammatory markers (calprotectin).

Results: C4 concentrations were increased in 10 CD (23%) (range: 70.8-269.3 ng/mL) but only one UC patient (72.9 ng/mL). CD patients with diarrhea (n=12) had higher C4-values compared to those without (76.9 vs. 30.4 ng/mL; p=0.0043). Ileal resection in CD patients (n=10) was associated with increased C4 concentrations (81.2 vs. 24.3 ng/mL, p=0.0004). No correlation was found between C4 values and inflammatory markers. Six of 7 CD patients with persistent diarrhea but quiescent disease (PCDAI ≤12.5) had C4 values indicating BAM.

Conclusion: Elevated C4 concentrations indicating BAM are common in children with CD. They are associated with ileal resection and non-bloody diarrhea in the absence of active disease or elevated inflammatory markers. The C4-test identifies a subgroup of CD patients with persistent diarrhea in spite of clinical remission which may benefit from bile acid binding therapy.

Keywords: 7α-Hydroxy-4-cholesten-3-one;; BAM;; C4-Test;; Pediatric IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bile Acids and Salts / metabolism*
  • Biomarkers / metabolism
  • Child
  • Child, Preschool
  • Cholestenones / metabolism*
  • Chromatography, High Pressure Liquid
  • Feces / chemistry
  • Female
  • Humans
  • Inflammatory Bowel Diseases / diagnosis
  • Inflammatory Bowel Diseases / metabolism*
  • Intestinal Mucosa / metabolism*
  • Intestines / pathology
  • Leukocyte L1 Antigen Complex / metabolism
  • Male
  • Reproducibility of Results
  • Severity of Illness Index
  • Young Adult

Substances

  • Bile Acids and Salts
  • Biomarkers
  • Cholestenones
  • Leukocyte L1 Antigen Complex
  • 7 alpha-hydroxy-4-cholesten-3-one