Department of Internal Medicine, Zealand University Hospital, Køge, Denmark.
Faculty of Health and Human Sciences, University of Copenhagen, Copenhagen, Denmark.
Aliment Pharmacol Ther. 2017 Jun;45(11):1433-1442. doi: 10.1111/apt.14056. Epub 2017 Apr 5.
Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation.
To explore if an impaired FGF19 response identifies primary bile acid diarrhoea.
Eight patients with primary bile acid diarrhoea and eight healthy volunteers ingested (i) a meal plus 1250 mg chenodeoxycholic acid (CDCA), (ii) 1250 mg CDCA or (iii) the meal. Blood was sampled at fasting and repeatedly after stimulation. We analysed FGF19 by enzyme-linked immunosorbent assay and bile acids including 7α-hydroxy-4-cholesten-3-one by liquid chromatography-tandem mass spectrometry.
Stimulation with the meal plus CDCA increased median FGF19 in healthy volunteers from fasting 62 pg/mL [interquartile range (IQR): 41-138] to 99 pg/mL (IQR: 67-147; P = 0.012) after 90 min and peaked after 150 min at 313 pg/mL (IQR: 54-512). This response was impaired in primary bile acid diarrhoea patients [fasting 56 pg/mL (IQR: 42-79); 90 min: 48 pg/mL [IQR: 37-63); 150 min: 57 pg/mL (48-198)]. Receiver operating characteristics (ROC ) for fasting FGF19 was 0.55 (P = 0.75) and at 90 min 0.84 (P = 0.02). The difference in FGF19 from fasting to 90 min after the meal plus CDCA separated the groups (ROC 1.0; P = 0.001). 7α-hydroxy-4-cholesten-3-one was elevated in primary bile acid diarrhoea (P = 0.038) and not significantly affected by stimulation.
The FGF19 response following chenodeoxycholic acid plus meal is impaired in primary bile acid diarrhoea. This may provide a biochemical diagnostic test.
胆酸腹泻的诊断不足，需要更好的诊断测试。空腹血清成纤维细胞生长因子 19（FGF19）的诊断价值不足，但刺激可能会改善这种情况。
探讨 FGF19 反应受损是否能识别原发性胆酸腹泻。
8 例原发性胆酸腹泻患者和 8 名健康志愿者分别（i）进食加 1250mg 鹅脱氧胆酸（CDCA）、（ii）1250mg CDCA 或（iii）进食。刺激前和刺激后空腹和多次采血。我们通过酶联免疫吸附测定法分析 FGF19，通过液相色谱-串联质谱法分析胆汁酸，包括 7α-羟基-4-胆甾烯-3-酮。
CDCA 加膳食刺激使健康志愿者的空腹 FGF19 中位数从 62pg/mL（IQR：41-138）增加到 99pg/mL（IQR：67-147；P=0.012），90min 后达到峰值 313pg/mL（IQR：54-512）。这种反应在原发性胆酸腹泻患者中受损[空腹 56pg/mL（IQR：42-79）；90min：48pg/mL（IQR：37-63）；150min：57pg/mL（48-198）]。空腹 FGF19 的 ROC 为 0.55（P=0.75），90min 时为 0.84（P=0.02）。CDCA 加膳食后空腹 FGF19 与 90min 之间的差异可将两组分开（ROC 1.0；P=0.001）。7α-羟基-4-胆甾烯-3-酮在原发性胆酸腹泻中升高（P=0.038），但刺激无明显影响。
CDCA 加膳食后 FGF19 的反应在原发性胆酸腹泻中受损。这可能提供一种生化诊断测试。
