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

ABSTRACT: The serum biomarkers, elevated 7?C4 (C4) and decreased FGF19, have been proposed as screening tests for bile acid diarrhoea.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).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.Among the 101 patients, there was a negative correlation between serum C4 and FGF19 (Rs=-.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.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.

SUBMITTER: Vijayvargiya P

PROVIDER: S-EPMC5555810 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Vijayvargiya P P Camilleri M M Carlson P P Lueke A A O'Neill J J Burton D D Busciglio I I Donato L L

Alimentary pharmacology & therapeutics 20170710 6

<h4>Background</h4>The serum biomarkers, elevated 7αC4 (C4) and decreased FGF19, have been proposed as screening tests for bile acid diarrhoea.<h4>Aim</h4>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).<h4>Methods</h4>We prospectively studied fasting serum C4 and FGF19 in 101 IBS-D patients; we reviewed data from 37 ...[more]

PMID: 28691284

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Project description:BACKGROUND & AIMS:The degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis. METHODS:Herein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis. RESULTS:We found that total and conjugated bile acids were significantly increased in patients with alcoholic hepatitis compared with controls. Serum FGF19 levels were strongly increased and gene expression of FGF19 was induced in biliary epithelial cells and ductular cells of patients with alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4 serum levels) was significantly decreased in patients with alcoholic hepatitis. Importantly, total and conjugated bile acids correlated positively with FGF19 and with disease severity (model for end-stage liver disease score). FGF19 correlated best with conjugated cholic acid, and model for end-stage liver disease score best with taurine-conjugated chenodeoxycholic acid. Univariate analysis demonstrated significant associations between FGF19 and bilirubin as well as gamma glutamyl transferase, and negative correlations between FGF19 and fibrosis stage as well as polymorphonuclear leukocyte infiltration, in all patients with alcoholic hepatitis. CONCLUSION:Serum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis, while de novo bile acid synthesis is suppressed. Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis in humans. LAY SUMMARY:Understanding the underlying mechanisms that drive alcoholic hepatitis is important for the development of new biomarkers and targeted therapies. Herein, we describe a molecule that is increased in patients with alcoholic hepatitis. Modulating the molecular pathway of this molecule might lead to promising targets for the treatment of alcoholic hepatitis.

Project description:The involvement of bile salt-fibroblast growth factor 19 (FGF19) signaling in human liver regeneration (LR) is not well studied. Therefore, we studied aspects of bile salt-FGF19 signaling shortly after liver resection in patients. We compared plasma bile salt and FGF19 levels in arterial, portal and hepatic venous blood, calculated venous-arterial differences (ΔVA), and determined hepatic transcript levels on two intra-operative time points: before (< 1 hour) and immediately after (> 2-3 hours) liver resection (i.e., following surgery). Postoperative bile salt and FGF19 levels were assessed on days 1, 2, and 3. LR was studied by computed tomography (CT)-liver volumetry. Following surgery, the liver, arterial, and portal bile salt levels were elevated (P < 0.05). Furthermore, an increased amount of bile salts was released in portal blood and extracted by the remnant liver (P < 0.05). Postoperatively, bile salt levels were elevated from day 1 onward (P < 0.001). For FGF19, intra-operative or postoperative changes of ΔVA or plasma levels were not observed. The bile salt-homeostatic regulator farnesoid X receptor (FXR) was markedly up-regulated following surgery (P < 0.001). Cell-cycle re-entry priming factors (interleukin 6 [IL-6], signal transducer and activator of transcription 3 [STAT3], and cJUN) were up-regulated following surgery and were positively correlated with FXR expression (P < 0.05). Postoperative hyperbilirubinemia was preceded by postsurgery low FXR and high Na+/Taurocholate cotransporting polypeptide (NTCP) expression in the remnant liver coupled with higher liver bile salt content (P < 0.05). Finally, bile salt levels on postoperative day 1 were an independent predictor of LR (P < 0.05). Conclusion: Systemic, portal, and liver bile salt levels are rapidly elevated after liver resection. Postoperative bile salts were positively associated with liver volume gain. In the studied time frame, FGF19 levels remained unaltered, suggesting that FGF19 plays a minor role in human LR. These findings indicate a more relevant role of bile salts in human LR.

Dataset Information

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

Publications

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

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