1. Orchestration of Tryptophan-Kynurenine Pathway, Acute Decompensation, and Acute-on-Chronic Liver Failure in Cirrhosis
- Author
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Claria, J., Moreau, R., Fenaille, F., Amoros, A., Junot, C., Gronbaek, H., Coenraad, M.J., Pruvost, A., Ghettas, A., Chu-Van, E., Lopez-Vicario, C., Oettl, K., Caraceni, P., Alessandria, C., Trebicka, J., Pavesi, M., Deulofeu, C., Albillos, A., Gustot, T., Welzel, T.M., Fernandez, J., Stauber, R.E., Saliba, F., Butin, N., Colsch, B., Moreno, C., Durand, F., Nevens, F., Banares, R., Benten, D., Gines, P., Gerbes, A., Jalan, R., Angeli, P., Bernardi, M., Arroyo, V., EASL Clif Consortium, Grifols Chair European Fdn Study C, Clària, Joan, Moreau, Richard, Fenaille, Françoi, Amorós, Alex, Junot, Christophe, Gronbaek, Henning, Coenraad, Minneke J, Pruvost, Alain, Ghettas, Aurélie, Chu-Van, Emeline, López-Vicario, Cristina, Oettl, Karl, Caraceni, Paolo, Alessandria, Carlo, Trebicka, Jonel, Pavesi, Marco, Deulofeu, Carme, Albillos, Agustin, Gustot, Thierry, Welzel, Tania M, Fernández, Javier, Stauber, Rudolf E, Saliba, Faouzi, Butin, Noémie, Colsch, Benoit, Moreno, Christophe, Durand, Françoi, Nevens, Frederik, Bañares, Rafael, Benten, Daniel, Ginès, Pere, Gerbes, Alexander, Jalan, Rajiv, Angeli, Paolo, Bernardi, Mauro, Arroyo, Vicente, Grifols Chair, Partenaires INRAE, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Université Paris Diderot - Paris 7 (UPD7), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris Saclay (COmUE), Aarhus University Hospital, Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Institut National de la Recherche Agronomique (INRA), Medical University Graz, Department of Medical and Surgical Sciences, Universita degli Studi di Padova, San Giovanni Battista Hosp, Div Gastroenterol & Hepatol, Turin, Italy, Rheinische Friedrich-Wilhelms-Universität Bonn, Hospital Universitario, Université libre de Bruxelles (ULB), Goethe-Universität Frankfurt am Main, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Université Catholique de Louvain = Catholic University of Louvain (UCL), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Univ Hosp LMU Munich, Liver Ctr Munich, Dept Med 2, Munich, Germany, University College of London [London] (UCL), Universita di Padova, ICREA Academia Award, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universiteit Leiden-Universiteit Leiden, and Università degli Studi di Padova = University of Padua (Unipd)
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Liver Cirrhosis ,Male ,0301 basic medicine ,Cirrhosis ,Kynurenine pathway ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,severity ,Decompensated cirrhosis ,Systemic inflammation ,Gastroenterology ,Tryptophan -- blood ,chemistry.chemical_compound ,0302 clinical medicine ,hepatic-encephalopathy ,Prospective Studies ,Renal Insufficiency ,Indoleamine 2,3-dioxygenase ,Hepatic encephalopathy ,Kynurenine ,Liver Cirrhosis -- blood -- complications -- mortality -- physiopathology ,systemic inflammation ,Europe -- epidemiology ,Kynurenine -- blood ,Hepatic Encephalopathy -- blood -- complications ,Tryptophan ,Bacterial Infections -- blood -- complications ,Immunosuppression ,Bacterial Infections ,Sciences bio-médicales et agricoles ,Middle Aged ,Acute-On-Chronic Liver Failure -- blood -- etiology ,metabolomics ,3. Good health ,Europe ,chromatography ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,metabolomic ,medicine.medical_specialty ,indoleamine 2,3-dioxygenase ,Decompensated cirrhosi ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,organ failure ,Decompensation ,plasma ,Aged ,Inflammation ,Inflammation -- blood -- complications ,Renal Insufficiency -- blood -- complications ,Hepatology ,business.industry ,Acute-On-Chronic Liver Failure ,blockade ,medicine.disease ,mortality ,kynurenine ,030104 developmental biology ,chemistry ,Case-Control Studies ,Hepatic Encephalopathy ,business ,metabolism - Abstract
Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute-on-chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan/system damage and immunosuppression. In the current study, we aimed to characterize the KP in patients with cirrhosis, in whom this pathway is poorly known. The serum levels of Trp, key KP metabolites (kynurenine and kynurenic and quinolinic acids), and cytokines (SI markers) were measured at enrollment in 40 healthy subjects, 39 patients with compensated cirrhosis, 342 with AD (no ACLF) and 180 with ACLF, and repeated in 258 patients during the 28-day follow-up. Urine KP metabolites were measured in 50 patients with ACLF. Serum KP activity was normal in compensated cirrhosis, increased in AD and further increased in ACLF, in parallel with SI; it was remarkably higher in ACLF with kidney failure than in ACLF without kidney failure in the absence of differences in urine KP activity and fractional excretion of KP metabolites. The short-term course of AD and ACLF (worsening, improvement, stable) correlated closely with follow-up changes in serum KP activity. Among patients with AD at enrollment, those with the highest baseline KP activity developed ACLF during follow-up. Among patients who had ACLF at enrollment, those with immune suppression and the highest KP activity, both at baseline, developed nosocomial infections during follow-up. Finally, higher baseline KP activity independently predicted mortality in patients with AD and ACLF. Conclusion: Features of KP activation appear in patients with AD, culminate in patients with ACLF, and may be involved in the pathogenesis of ACLF, clinical course, and mortality., info:eu-repo/semantics/published
- Published
- 2019
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