Commentary: fibroblast growth factor 19 in patients with bile acid diarrhoea

The recent paper by Pattni et al.1 has the potential to change clinical practice in the assessment of patients with unexplained diarrhoea, often attributed to diarrhoea-predominant irritable bowel syndrome (IBS-D).2 It builds on the seminal observations by Walters et al.3 that ileal enterocyte secretion of fibroblast growth factor 19 (FGF-19) is deficient in patients with so-called secondary bile acid diarrhoea (BAD). In their prospective comparison of serum FGF-19 and 75SeHCAT retention, Pattni et al. confirm the overall relationship between the two measurements, and the inverse relationship (as previously demonstrated by several groups)4, 5 between serum FGF-19 and serum 7α-hydroxy-4-cholesten-3-one (C4). These data reinforce the prior conclusion that reduced ileal FGF-19 secretion is a feature of BAD.3 There are four tools that directly measure BA malabsorption: 14C-glycocholate breath and stool test, 75SeHCAT, C4, and faecal total and individual BAs. The pros and cons of these tests are summarised in Table 1.6 The most widely used method for diagnosis of BAD is a therapeutic trial of bile acid binders with symptom improvement. The paper by Pattni et al. has additional value, as it assesses the potential to use serum FGF-19 as a screen for BAD. The ROC curves showing FGF-19 ≤145 pg/mL to predict 75SeHCAT values <10% or <5% were 58% (95% CI: 42–72) and 67% (95% CI 38–87). A full response to bile acid sequestrants occurred in 15 of the 16 patients with FGF-19 ≤145 pg/mL, but in only 50% of those with higher values. The FGF-19 assay is based on a simple, inexpensive commercial ELISA; in contrast, other diagnostic methods (C4 and faecal bile acids) require high-performance liquid chromatography with tandem mass spectrometry and/or 48 h stool collection. The ability to screen for BAD with serum FGF-19 could dramatically change clinical practice in the assessment and management of diarrhoea in patients with either inflammatory bowel disease or IBS-D. Declaration of personal and funding interests: Dr Camilleri is funded by NIH DK92179.