fbd32b6f68756fc664b715c8c9c2e6e6 308593.pdf 5d242b31bd7b17188190fa8baa373d43693105ea 308593.pdf 41f56dff38e4c810ea0a2f9bca6d581384979be6bf60a722b646d88a1c6f2812 308593.pdf Title: Biomarkers of Frailty in Patients with Advanced Chronic Liver Disease Undergoing a Multifactorial Intervention Consisting of Home Exercise, Branched-Chain Amino Acids, and Probiotics Subject: Frailty in cirrhosis or advanced chronic liver disease (ACLD) is a relevant prognostic factor. In the present study, we aimed to analyze potential biomarkers associated with frailty and its improvement in patients with ACLD. We analyzed the serum of outpatients with ACLD who participated in a previous study (Román, Hepatol Commun 2024) in which frailty was assessed using the liver frailty index (LFI), and patients who were frail or prefrail were randomized to a multifactorial intervention (home exercise, branched-chain amino acids, and probiotics) or control for 12 months. We determined a biomarker battery of inflammation, bacterial translocation, and liver damage in blood and urine and blood metabolomics by 1H-NMR. Thirty-seven patients were included. According to the LFI, 32 patients were frail or prefrail, and 5 were robust. At baseline, LFI correlated with LBP, sCD163, mtDNA, FGF-21, urinary NGAL, urinary claudin-3, and the metabolites mannose, ethanol, and isoleucine. During the study, patients in the intervention group showed an improvement in LFI and a decrease in CRP, LBP, sCD163, and ccK18 compared to the control group. Metabolomics showed a decrease in dimethyl sulfone and creatinine and an increase in malonate, ornithine, isoleucine, and valine in the intervention group. We conclude that frailty in patients with ACLD is associated with biomarkers of systemic inflammation, bacterial translocation, and liver damage, and alterations of amino acid and short-chain fatty acid metabolism. Keywords: metabolomics; exercise; branched-chain amino acids; probiotics; inflammation Author: Luca Laghi, Maria Àngels Ortiz, Giacomo Rossi, Eva Román, Carlo Mengucci, Elisabet Cantó, Lucia Biagini, Elisabet Sánchez, Maria Mulet, Álvaro García-Osuna, Eulàlia Urgell, Naujot Kaur, Maria Poca, Josep Padrós, Maria Josep Nadal, Berta Cuyàs, Edilmar Alvarado, Silvia Vidal, Elena Juanes, Andreu Ferrero-Gregori, Àngels Escorsell and German Soriano Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Nov 6 09:50:10 2024 CET ModDate: Wed Nov 6 09:55:21 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1827137 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BGZEDF+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 BZNCWO+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 UFFYKF+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 QSBUKA+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 OMNWBO+VnURWPalladioL Type 1 Custom yes yes yes 32 0 OJYQXC+CMSY10 Type 1 Builtin yes yes yes 62 0 VVSYYB+EURM10 Type 1 Builtin yes yes yes 70 0 NMNOHK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 87 0 NMNOHL+PalatinoLinotype CID TrueType Identity-H yes yes yes 90 0 NMNOHM+PalatinoLinotype TrueType WinAnsi yes yes no 96 0 NMNOHO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 99 0 NMNONN+PalatinoLinotype TrueType MacRoman yes yes no 102 0 MDIKPC+CMBSY10 Type 1 Builtin yes yes yes 109 0 NMNOHK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 123 0 NMNOHL+PalatinoLinotype CID TrueType Identity-H yes yes yes 126 0 NMNOHM+PalatinoLinotype TrueType WinAnsi yes yes no 132 0 NMNOHO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 135 0 NMNONN+PalatinoLinotype TrueType MacRoman yes yes no 138 0 NMNOHK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 155 0 NMNOHL+PalatinoLinotype CID TrueType Identity-H yes yes yes 158 0 NMNOHM+PalatinoLinotype TrueType WinAnsi yes yes no 164 0 NMNOHO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 167 0 NMNONN+PalatinoLinotype TrueType MacRoman yes yes no 170 0 NMNOHK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 186 0 NMNOHM+PalatinoLinotype TrueType WinAnsi yes yes no 189 0 NMNOHO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 192 0 NMNONN+PalatinoLinotype TrueType MacRoman yes yes no 195 0 NMNOHK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 214 0 NMNOHM+PalatinoLinotype TrueType WinAnsi yes yes no 217 0 NMNOHO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 220 0 NMNONN+PalatinoLinotype TrueType MacRoman yes yes no 223 0 NMNOHK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 239 0 NMNOHL+PalatinoLinotype CID TrueType Identity-H yes yes yes 242 0 NMNOHM+PalatinoLinotype TrueType WinAnsi yes yes no 248 0 NMNOHO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 251 0 NMNONN+PalatinoLinotype TrueType MacRoman yes yes no 254 0 NMNOHK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 270 0 NMNOHL+PalatinoLinotype CID TrueType Identity-H yes yes yes 273 0 NMNOHM+PalatinoLinotype TrueType WinAnsi yes yes no 279 0 NMNOHO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 282 0 NMNONN+PalatinoLinotype TrueType MacRoman yes yes no 285 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-03-01 02:49:31 CET RepresentationInformation: 308593.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-02-28 12:53:12 CET Size: 1827137 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 537 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Patients and Methods Destination: section.2 Children: Item: Title: Study Design and Patient Selection Destination: subsection.2.1 Item: Title: Methods for Biomarkers Analysis Destination: subsection.2.2 Item: Title: Metabolomics by 1H-NMR Destination: subsection.2.3 Item: Title: Statistical Analysis Destination: subsection.2.4 Item: Title: Results Destination: section.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Biomarkers of Frailty in Patients with Advanced Chronic Liver Disease Undergoing a Multifactorial Intervention Consisting of Home Exercise, Branched-Chain Amino Acids, and Probiotics Author: Luca Laghi, Maria Àngels Ortiz, Giacomo Rossi, Eva Román, Carlo Mengucci, Elisabet Cantó, Lucia Biagini, Elisabet Sánchez, Maria Mulet, Álvaro García-Osuna, Eulàlia Urgell, Naujot Kaur, Maria Poca, Josep Padrós, Maria Josep Nadal, Berta Cuyàs, Edilmar Alvarado, Silvia Vidal, Elena Juanes, Andreu Ferrero-Gregori, Àngels Escorsell and German Soriano Subject: Frailty in cirrhosis or advanced chronic liver disease (ACLD) is a relevant prognostic factor. In the present study, we aimed to analyze potential biomarkers associated with frailty and its improvement in patients with ACLD. We analyzed the serum of outpatients with ACLD who participated in a previous study (Román, Hepatol Commun 2024) in which frailty was assessed using the liver frailty index (LFI), and patients who were frail or prefrail were randomized to a multifactorial intervention (home exercise, branched-chain amino acids, and probiotics) or control for 12 months. We determined a biomarker battery of inflammation, bacterial translocation, and liver damage in blood and urine and blood metabolomics by 1H-NMR. Thirty-seven patients were included. According to the LFI, 32 patients were frail or prefrail, and 5 were robust. At baseline, LFI correlated with LBP, sCD163, mtDNA, FGF-21, urinary NGAL, urinary claudin-3, and the metabolites mannose, ethanol, and isoleucine. During the study, patients in the intervention group showed an improvement in LFI and a decrease in CRP, LBP, sCD163, and ccK18 compared to the control group. Metabolomics showed a decrease in dimethyl sulfone and creatinine and an increase in malonate, ornithine, isoleucine, and valine in the intervention group. We conclude that frailty in patients with ACLD is associated with biomarkers of systemic inflammation, bacterial translocation, and liver damage, and alterations of amino acid and short-chain fatty acid metabolism. 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