Background: Bile acid malabsorption (BAM) is a common feature of Crohn's disease (CD). We aimed to determine whether BAM develops only in patients with a resected distal ileum or if it also occurs in patients who have not undergone surgery for CD.
Methods: The study included 347 patients with CD or ulcerative colitis (UC) and 119 healthy subjects (controls). BAM was assessed by measurement of serum levels of 7α-hydroxycholest-4-en-3-one (C4) and fibroblast growth factor 19 (FGF19). We surveyed members of the European Crohn's and Colitis Organization and International Organization for the Study of Inflammatory Bowel Disease to collect current information about BAM diagnosis.
Results: The severity of BAM was associated with resection of the distal ileum. Compared with controls, patients who received moderate or extensive ileal resection had significantly increased levels of serum C4 (12 versus 62 versus 243 μg/L, respectively; P < 0.001). However, BAM was also present in a substantial number of the patients with CD who were not treated by surgery who had ileitis or colitis (14% and 11%, respectively). There was an indirect, proportional relationship between levels of C4 and FGF19 (P < 0.001).
Conclusions: The most severe BAM occurs in CD patients after resection of the distal ileum, but BAM can occur in surgically untreated CD patients, regardless of disease localization. Laboratory tests for BAM should become a part of the algorithm for diagnosis of CD to identify patients who might respond to therapies such as bile acid sequestrants. FGF19 appears to be a reliable marker of BAM.
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http://dx.doi.org/10.1002/ibd.21502 | 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.
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