Measurement of serum 7alpha-hydroxy-4-cholesten-3-one (or 7alphaC4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography-tandem mass spectrometry - PubMed (original) (raw)

Measurement of serum 7alpha-hydroxy-4-cholesten-3-one (or 7alphaC4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography-tandem mass spectrometry

M Camilleri et al. Neurogastroenterol Motil. 2009 Jul.

Abstract

Bile acid malabsorption (BAM) is reported in up to 50% of patients with functional diarrhoea and irritable bowel syndrome with diarrhoea (IBS-D). Serum 7alpha-hydroxy-4-cholesten-3-one (7alphaHCO or 7alphaC4), an indirect measurement of hepatic bile acid synthesis, has been validated as a measurement of BAM relative to the (75)SeHCAT retention test. Our aim was to develop a serum 7alphaC4 assay, normal values, and compare results from healthy controls, patients with ileal Crohn's disease or resection, and patients with IBS-D or IBS with constipation (IBS-C). Stored serum samples were used from adult men and women in the following groups: 111 normal healthy controls, 15 IBS-D, 15 IBS-C, 24 with distal ileal Crohn's disease and 20 with distal ileal resection for Crohn's disease. We adapted a published high pressure liquid chromatography, tandem mass spectrometry (HPLC-MS/MS) assay. The HPLC-MS/MS assay showed good linearity in concentration range 0-200 ng mL(-1), sensitivity (lowest limit of detection 0.04 ng mL(-1)), and high analytical recovery (average 99%, range 93-107%). The 5th to 95th percentile for 111 normal healthy controls was 6-60.7 ng mL(-1). There were significant overall group differences (anovaon ranks, P < 0.001), with significantly higher values for terminal ileal disease or resection. There were significant differences between health and IBS (anova, P = 0.043) with higher mean values in IBS-D relative to controls (rank sum test, P = 0.027). We have established a sensitive non-isotopic assay based on HPLC-MS/MS, determined normal 7alphaC4 values, and identified increased 7alphaC4 in IBS-D and in distal ileal resection and disease. This assay has potential as a non-invasive test for BAM in IBS.

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Figures

Figure 1

Figure 1

Histogram plots of all groups showing the percentage of each group with serum 7αC4 (ng/mL) in different concentrations. Note that values above 60ng/mL fall outside the normal range. Thus, >50% of patients with distal ileal disease or resection and 20% of patients with IBS-D had abnormal serum 7αC4.

Figure 2

Figure 2

Comparison of serum 7αC4 (ng/mL) in IBS and healthy volunteers. Data show median and interquartile (box) range, 5th and 95th percentiles and outliers (individual symbols). There are overall significant group differences (ANOVA on ranks, p=0.043), with a borderline significant difference between the healthy volunteer and IBS-D group (Mann-Whitney Rank Sum Test, p=0.027).

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