Improved HPLC Analysis of Serum 7α-Hydroxycholest-4-en-3-one, a Marker of Bile Acid Malabsorption

Leníček, Martin; Juklova, M.; Zelenka, Jaroslav; Kovář, J.; Lukáš, Milan; Bortlík, Martin; Vı́tek, Libor

doi:10.1373/clinchem.2007.100107

Cited by 17 publications

(7 citation statements)

References 6 publications

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“…The detection limit of bile acid intermediates in this assay is 0.05 μmol/L. Plasma FGF19 was determined as described previously (Schreuder et al 2010 ) and plasma C4 was measured by LC-MS based on the original method of (Lenicek et al 2008 ), with a detection limit of 1 ng/mL. For detailed LC-MS conditions see supplementary methods.…”

Section: Methodsmentioning

confidence: 99%

Cholic acid therapy in Zellweger spectrum disorders

Berendse

Klouwer

Koot

et al. 2016

J of Inher Metab Disea

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IntroductionZellweger spectrum disorders (ZSDs) are characterized by a failure in peroxisome formation, caused by autosomal recessive mutations in different PEX genes. At least some of the progressive and irreversible clinical abnormalities in patients with a ZSD, particularly liver dysfunction, are likely caused by the accumulation of toxic bile acid intermediates. We investigated whether cholic acid supplementation can suppress bile acid synthesis, reduce accumulation of toxic bile acid intermediates and improve liver function in these patients.MethodsAn open label, pretest-posttest design study was conducted including 19 patients with a ZSD. Participants were followed longitudinally during a period of 2.5 years prior to the start of the intervention. Subsequently, all patients received oral cholic acid and were followed during 9 months of treatment. Bile acids, peroxisomal metabolites, liver function and liver stiffness were measured at baseline and 4, 12 and 36 weeks after start of cholic acid treatment.ResultsDuring cholic acid treatment, bile acid synthesis decreased in the majority of patients. Reduced levels of bile acid intermediates were found in plasma and excretion of bile acid intermediates in urine was diminished. In patients with advanced liver disease (n = 4), cholic acid treatment resulted in increased levels of plasma transaminases, bilirubin and cholic acid with only a minor reduction in bile acid intermediates.ConclusionsOral cholic acid therapy can be used in the majority of patients with a ZSD, leading to at least partial suppression of bile acid synthesis. However, caution is needed in patients with advanced liver disease due to possible hepatotoxic effects.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-016-9962-9) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Cholic acid therapy in Zellweger spectrum disorders

Berendse

Klouwer

Koot

et al. 2016

J of Inher Metab Disea

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“…Baseline interleukin-6 (IL-6) levels were determined by sandwich ELISA (Sanquin, Amsterdam, The Netherlands). 7␣-Hydroxy-4-cholesten-3-one (C4) levels, a plasma marker for bile salt synthesis, were determined at baseline and at 4 and 5 h after oral fat intake as previously described (19). C4 levels were expressed relative to total cholesterol, because their ratio was shown to be a more accurate marker of bile salt synthesis (15).…”

Section: Methodsmentioning

confidence: 99%

The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance

Schreuder

Marsman²,

Leníček

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Intestinal FGF19 has emerged as a novel endocrine regulator of hepatic bile salt and lipid metabolism. In patients with nonalcoholic fatty liver disease (NAFLD) hepatic lipid metabolism is deranged. A possible role of FGF19 in NAFLD has not been reported yet. In this study, we assessed intestinal FGF19 production and the hepatic response to FGF19 in NAFLD patients with and without insulin resistance [homeostasis model of assessment (HOMA) score > or =2.5 (n = 12) and HOMA score <2.5 (n = 8), respectively]. To this end, NAFLD patients received a standardized oral fat challenge. Postprandial excursions of triglycerides, bile salts, and FGF19 were monitored, and plasma levels of a marker for bile salt synthesis (7alpha-hydroxy-4-cholesten-3-one) were determined. Fasted FGF19 levels were comparable in a control group of healthy volunteers (n = 15) and in NAFLD patients (0.26 +/- 0.28 vs. 0.18 +/- 0.09 ng/ml, respectively, P = 0.94). Postprandial FGF19 levels in both controls and NAFLD patients peaked between 3-4 h and were three times higher than baseline levels. The areas under the postprandial FGF19 curve were similar in controls and in the HOMA score-based NAFLD subgroups. In NAFLD patients with HOMA score <2.5, the postprandial increase in plasma FGF19 was accompanied by a lowering of plasma levels of 7alpha-hydroxy-4-cholesten-3-one (-30%, P = 0.015). This anticipated decline was not observed in insulin-resistant NAFLD patients (+10%, P = 0.22). In conclusion, patients with NAFLD show an unimpaired intestinal FGF19 production. However, the hepatic response to FGF19 is impaired in NAFLD patients with insulin resistance (HOMA score > or =2.5). This impaired hepatic response to FGF19 may contribute to the dysregulation of lipid homeostasis in NAFLD.

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“…The C4 concentration was measured by high-performance liquid chromatography (HPLC), as previously described. 27 Total and HDL cholesterol levels were measured on a modular automatic analyzer (Roche Diagnostics, Switzerland) using commercially available kits (Cholesterol liquicolor, and HDL Cholesterol liquicolor, respectively; both Human GmbH, Germany). Serum FGF19 levels were measured by enzyme-linked immunosorbent assay (ELISA) (FGF19 Quantikine ELISA kit, R&D Systems, Minneapolis, MN) in 341 subjects, from whom an additional serum aliquot was available.…”

Section: Biochemical Analysesmentioning

confidence: 99%