P315. The role of FGF19 in the assessment of diarrhoea and disease activity in non-ileal resected Crohn's disease
J. Nolan1, I. Johnston1, J.H. Zhang1, T. Dew2, P. Dixon3, C. Williamson3, J.R. Walters1, 1Imperial College London, Gastroenterology, London, United Kingdom, 2King's College Hospital, Biochemistry, London, United Kingdom, 3Imperial College, Institute of Reproductive and Developmental Biology, London, United Kingdom
Bile acid malabsorption (BAM) occurs in 90% of patients suffering from chronic diarrhoea after ileal resection in Crohn's disease (CD). In response to BA absorption, the normal ileum produces Fibroblast Growth Factor 19 (FGF19), a negative regulator of hepatic BA synthesis. Ileal BA transporter expression is reduced in CD and inflammatory cytokines have been shown to inhibit the transcription of FGF19 in vitro. It has recently been shown that reduced fasting serum FGF19 levels may be a sensitive and specific marker of BAM in CD. In addition to BAM, reduced FGF19 may worsen bile acid diarrhoea in CD if excess BA is produced.
We measured fasting FGF19 levels in 35 non-ileal resected CD (NR-CD) patients (Quantikine ELISA R+D systems). Diarrhoea symptoms and disease activity using the Harvey–Bradshaw index were recorded. In 11 patients with active disease and diarrhoea levels were measured before and after treatment (biologics or corticosteroids). We also compared the bile acid (BA) induced FGF19 expression in ileal biopsies obtained during colonoscopy from patients with NR-CD (n = 6) and control patients (n = 17). Paired sets of ileal biopsies were incubated for 6 hours with and without BAs Chenodeoxycholic acid (CDCA) or Glycochenodeoxycholic acid (GCDCA). RT-qPCR was used to compare the induction of FGF19 transcript expression (relative to GAPDH).
19/35 patients were experiencing a flare of disease activity at the time of assessment 12/19 of which had acute watery diarrhoea (loose stool frequency >3/day). FGF19 levels were significantly lower in NR-CD patients with diarrhoea compared to those without (median 86 pg/ml, range 20–169 vs 145 pg/ml, range 3–338, p = 0.03) and compared to a cohort of idiopathic diarrhoea control patients (p ≤ 0.0001, Mann Whitney). Out of 11 patients with pre and post treatment levels, median FGF19 levels significantly increased following treatment and resolution of diarrhoea in 6 patients with ileal disease (p = 0.03, Wilcoxon) but not in the remaining 5 with colonic disease. Significant inverse correlations between FGF19 levels and stool frequency (Spearman p = 0.04), Bristol stool form (p = 0.03) and CRP (p = 0.03) were observed. There was a trend towards reduced BA induced FGF19 expression in ileal biopsies from patients with CD compared to controls (p = 0.1, Mann–Whitney).
Reduced FGF19 levels are associated with active disease and symptoms of watery diarrhoea in NR-CD. This is likely to reflect the effects of inflammation associated with active disease on the absorption of BA or ileal FGF19 expression. A significant number of patients with NR-CD may benefit from treatments to reduce excess faecal BA during a flare of disease activity.