Background: Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation.
Aim: To explore if an impaired FGF19 response identifies primary bile acid diarrhoea.
Methods: Eight patients with primary bile acid diarrhoea and eight healthy volunteers ingested (i) a meal plus 1250 mg chenodeoxycholic acid (CDCA), (ii) 1250 mg CDCA or (iii) the meal. Blood was sampled at fasting and repeatedly after stimulation. We analysed FGF19 by enzyme-linked immunosorbent assay and bile acids including 7α-hydroxy-4-cholesten-3-one by liquid chromatography-tandem mass spectrometry.
Results: Stimulation with the meal plus CDCA increased median FGF19 in healthy volunteers from fasting 62 pg/mL [interquartile range (IQR): 41-138] to 99 pg/mL (IQR: 67-147; P = 0.012) after 90 min and peaked after 150 min at 313 pg/mL (IQR: 54-512). This response was impaired in primary bile acid diarrhoea patients [fasting 56 pg/mL (IQR: 42-79); 90 min: 48 pg/mL [IQR: 37-63); 150 min: 57 pg/mL (48-198)]. Receiver operating characteristics (ROC ) for fasting FGF19 was 0.55 (P = 0.75) and at 90 min 0.84 (P = 0.02). The difference in FGF19 from fasting to 90 min after the meal plus CDCA separated the groups (ROC 1.0; P = 0.001). 7α-hydroxy-4-cholesten-3-one was elevated in primary bile acid diarrhoea (P = 0.038) and not significantly affected by stimulation.
Conclusions: The FGF19 response following chenodeoxycholic acid plus meal is impaired in primary bile acid diarrhoea. This may provide a biochemical diagnostic test.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/apt.14056 | DOI Listing |
PLoS One
January 2025
Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Immunologic bile duct destruction is a pathogenic condition associated with vanishing bile duct syndrome (VBDS) after liver transplantation and hematopoietic stem-cell transplantation. As the bile acid receptor sphingosine 1-phosphate receptor 2 (S1PR2) plays a critical role in recruitment of bone marrow-derived monocytes/macrophages to sites of cholestatic liver injury, S1PR2 expression was examined using cultured macrophages and patient tissues. Bile canaliculi destruction precedes intrahepatic ductopenia; therefore, we focused on hepatocyte S1PR2 and the downstream RhoA/Rho kinase 1 (ROCK1) signaling pathway and bile canaliculi alterations using three-dimensional hepatocyte culture models that form obvious bile canaliculus-like networks.
View Article and Find Full Text PDFLiver Int
February 2025
Department of Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Hannover Medical School, Hannover, Germany.
Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.
Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.
Metabolites
January 2025
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Background/objectives: The transition from a non-lactating to a lactating state is a critical period for lipid metabolism in dairy cows. Danggui Buxue Tang (DBT), stimulating energy metabolism, ameliorates diseases related to lipid metabolism disorders and is expected to be an effective supplement for alleviating excessive lipid mobilisation in periparturient dairy cows. This study aimed to investigate the effects of supplemental DBT on serum biochemical indices, faecal microbial communities, and plasma metabolites in dairy cows.
View Article and Find Full Text PDFCurr Issues Mol Biol
January 2025
Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania.
Chronic pain is a debilitating condition affecting millions worldwide, often resulting from complex interactions between the nervous and immune systems. Recent advances highlight the critical role of metabolite-sensing G protein-coupled receptors (GPCRs) in various chronic pain types. These receptors link metabolic changes with cellular responses, influencing inflammatory and degenerative processes.
View Article and Find Full Text PDFJ Med Chem
January 2025
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, P. R. China.
Metabolic dysfunction-associated steatohepatitis (MASH) is a complex disease driven by diverse metabolic and inflammatory pathways. Farnesoid X receptor (FXR) is a promising target for MASH due to its role in bile acid and lipid metabolism, while HSD17B13 regulates liver lipid droplet homeostasis. However, the existing HSD17B13 inhibitors have several druglike property challenges due to the common phenolic structure, a key pharmacophore for the HSD17B13 inhibitor.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!