Performance characteristics of serum C4 and FGF19 measurements to exclude the diagnosis of bile acid diarrhoea in IBS‐diarrhoea and functional diarrhoea

Summary Background The serum biomarkers, elevated 7αC4 (C4) and decreased FGF19, have been proposed as screening tests for bile acid diarrhoea. Aim To analyse prevalence, specificity and reproducibility of fasting C4 and FGF19 in identifying bile acid diarrhoea in patients with irritable bowel syndrome with predominant diarrhoea or functional diarrhoea (summarised as IBS‐D). Methods We prospectively studied fasting serum C4 and FGF19 in 101 IBS‐D patients; we reviewed data from 37 of the 101 patients with prior fasting serum C4 and FGF19 and from 30 of the 101 patients with prior faecal bile acids per 48 hours. We compared results with normal values (C4 ≥52.5 ng/mL [n=184], FGF‐19 ≤61.7 pg/mL [n=50]). We used Spearman correlation and Bland‐Altman plots to appraise reproducibility. Results Among the 101 patients, there was a negative correlation between serum C4 and FGF19 ( R s=−.342, P =.0005). Bile acid diarrhoea was diagnosed in 10 patients based on elevated serum C4 levels (mean 23.5±23.1 [SD] ng/mL) and 21 patients based on decreased FGF19 levels (121.6±84.2 pg/mL). With replicate tests in patients with stable IBS‐D, 78% of C4 and 70% of FGF19 measurements remained concordant, with 3% and 11% respectively consistently positive for bile acid diarrhoea in the 101 patients. Compared to 48 hours faecal bile acids, specificity for C4 and FGF19 was 83% and 78%, respectively. Bland‐Altman plots demonstrated greater reliability of C4 than FGF19. Conclusions Among 101 patents with IBS‐D, fasting FGF19 and C4 levels had good specificity and negative predictive value, suggesting utility as screening tests to exclude bile acid diarrhoea.