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| Pàgina inicial > Articles > Articles publicats > Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis |
(Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Università di Bologna) (Universiteit van Amsterdam) (Hospital Universitari Vall d'Hebron) (Hospital Clínic i Provincial de Barcelona) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (University of Turin) (Università di Bologna) (University Paris Diderot) (Goethe University Frankfurt) (Universitat Autònoma de Barcelona. Departament de Medicina) (University of Padova) (Aarhus University) (University of Alberta) (Mayo Clinic (Rochester, Estats Units d'Amèrica)) (Hospital Clínic i Provincial de Barcelona)
| Data: | 2021 |
| Resum: | Patients with decompensated cirrhosis, particularly those with acute-on-chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE-SAFETY randomized, double-blind, placebo-controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography-tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan-kynurenine and carnitine beta-oxidation pathways. An ACLF-specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan-kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development. |
| Ajuts: | European Commission 731875 Instituto de Salud Carlos III PI20/00579 Instituto de Salud Carlos III PI18/00727 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-01281 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Publicat a: | Hepatology Communications, Vol. 6, Núm. 5 (May 2022) , p. 1100-1112, ISSN 2471-254X |
