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Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis

Authors :
Pose, Elisa
Solà, Elsa
Lozano, Juan J.
Juanola, Adrià
Sidorova, Julia
Zaccherini, Giacomo
Wit, Koos
Uschner, Frank
Tonon, Marta
Kazankov, Konstantin
Jiménez, Cesar
Campion, Daniela
Napoleone, Laura
Ma, Ann T.
Carol, Marta
Morales‐Ruiz, Manuel
Alessandria, Carlo
Beuers, Ulrich
Caraceni, Paolo
Francoz, Claire
Durand, François
Mookerjee, Rajeshwar P.
Trebicka, Jonel
Vargas, Victor
Piano, Salvatore
Watson, Hugh
Abraldes, Juan G.
Kamath, Patrick S.
Davis, Mark M.
Ginès, Pere
Schulz, M.
Ferstl, P.
Giovo, I.
Roux, O.
Simon‐Talero, M.
Pérez‐Guasch, M.
Rubio, A.B.
Cervera, M.
Martínez, S.
Fabrellas, N.
Pich, J.
Vives, A.
Avitabile, E.
Graupera, I.
Solé, C.
Bassegoda, O.
Gratacós‐Ginès, J.
Joyera, M.
Palacio, E.
Aban, M.
Lanzillotti, T.
Nicolao, G.
Chiappa, M.T.
Esnault, V.
Andrade, R.
Pavesi, M.
Korenjak, M.
Farrés, J.
Serra‐Burriel, M.
Angeli, P.
Pose E.
Sola E.
Lozano J.J.
Juanola A.
Sidorova J.
Zaccherini G.
de Wit K.
Uschner F.
Tonon M.
Kazankov K.
Jimenez C.
Campion D.
Napoleone L.
Ma A.T.
Carol M.
Morales-Ruiz M.
Alessandria C.
Beuers U.
Caraceni P.
Francoz C.
Durand F.
Mookerjee R.P.
Trebicka J.
Vargas V.
Piano S.
Watson H.
Abraldes J.G.
Kamath P.S.
Davis M.M.
Gines P.
Schulz M.
Ferstl P.
Giovo I.
Roux O.
Simon-Talero M.
Perez-Guasch M.
Rubio A.B.
Cervera M.
Martinez S.
Fabrellas N.
Pich J.
Vives A.
Avitabile E.
Graupera I.
Sole C.
Bassegoda O.
Gratacos-Gines J.
Joyera M.
Palacio E.
Aban M.
Lanzillotti T.
Nicolao G.
Chiappa M.T.
Esnault V.
Andrade R.
Pavesi M.
Korenjak M.
Farres J.
Serra-Burriel M.
Angeli P.
Gastroenterology and Hepatology
Graduate School
Tytgat Institute for Liver and Intestinal Research
Amsterdam Gastroenterology Endocrinology Metabolism
Source :
Pose, E, Solà, E, Lozano, J J, Juanola, A, Sidorova, J, Zaccherini, G, de Wit, K, Uschner, F, Tonon, M, Kazankov, K, Jiménez, C, Campion, D, Napoleone, L, Ma, A T, Carol, M, Morales-Ruiz, M, Alessandria, C, Beuers, U, Caraceni, P, Francoz, C, Durand, F, Mookerjee, R P, Trebicka, J, Vargas, V, Piano, S, Watson, H, Abraldes, J G, Kamath, P S, Davis, M M, Ginès, P & investigators of the LIVERHOPE Consortium 2022, ' Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis ', Hepatology Communications, vol. 6, no. 5, pp. 1100-1112 . https://doi.org/10.1002/hep4.1881, Hepatol Commun, Hepatology communications. Wiley-Blackwell Publishing Ltd
Publication Year :
2021

Abstract

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.

Details

ISSN :
2471254X
Volume :
6
Issue :
5
Database :
OpenAIRE
Journal :
Hepatology communications
Accession number :
edsair.doi.dedup.....6ed26e7196fd79662688514131a83ce1