Downregulation of Serum and Distal Ileum Fibroblast Growth Factor19 in Bile Acid Diarrhoea Patients

BAD on the Runs: Improved Diagnosis of Idiopathic Bile Acid Diarrhea

“…Chang et al [1] confirm in Chinese patients the utility of serum measurements of FGF19 and 7αC4 in the diagnosis of idiopathic BAD, providing normal values for these serological tests, which are generally close to the ULN reported from studies performed in the UK and USA. They confirm that ileal biopsies obtained from patients with idiopathic BAD have reduced FGF19 mRNA expression compared with controls.…”

“…Idiopathic bile acid diarrhea (type 2 BAD) is unrelated to diarrhea due to ileal disease or resection (type 1 BAD), or an association with intestinal or pancreatic disease or cholecystectomy (type 3 BAD). The study by Chang et al [1] published in this issue of Digestive Diseases and Sciences measured serum FGF19 protein concentration using a commercial enzyme-linked immunosorbent assay (FGF19 ELISA kit) and serum concentrations of the intermediate by-product of bile salt synthesis 7α-hydroxy-4-cholesten-3-one (7αC4) using an ultra-high performance liquid chromatography-mass spectrometry method (UPLC-MS/MS). Note that the circulating level of 7αC4 is an indirect marker of the rate of BA synthesis in hepatocytes that indirectly correlates with fecal BA excretion.…”

“…The etiopathogenetic mechanisms causing idiopathic BAD have been investigated in the past; further evidence is provided by Chang et al [1]. Walters et al [3] were the first to document the low levels of FGF19 and the reciprocal relationship between FGF19 and 7αC4.…”

“…One limitation of the study [1] is that serum 7αC4 was used as the standard to identify BAD and to assess the performance characteristics of serum FGF19; the prior literature had used other diagnostic methods: 75-selenium homocholic acid taurine ( 75 SeHCAT) retention at 7 days (not available in many countries including the USA) or 48 h fecal BA excretion using either total (> 2337 µmol/48 h) or primary BA > 10%, or a combination of total > 1000 µmol/48 h plus > 4% primary BA, or a successful therapeutic response to BA sequestrants. FGF19 assays are commercially available using a simple ELISA assay, in contrast to the more complicated LC/MS assay for serum 7αC4.…”

“…FGF19 assays are commercially available using a simple ELISA assay, in contrast to the more complicated LC/MS assay for serum 7αC4. Figure 1 in the article by Chang et al [1] illustrates the considerable overlap among serum 7αC4 levels in health, BAD and non-BAD, based on the current cohorts and the serum 7αC4 ULN. Future studies should continue to refine the serum FGF19 ULN diagnostic of BAD compared with one of the diagnostic methods listed above in order to better differentiate these populations, and also to replicate the results of Chang et al [1] in a separate cohort, especially the serum FGF19 ULN.…”