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Article Dans Une Revue Gut Année : 2023

Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET)

Carlos de la Peña-Ramirez
  • Fonction : Auteur
Ferran Aguilar
  • Fonction : Auteur
Juan-Jose Lozano
  • Fonction : Auteur
Cristina Sánchez-Garrido
  • Fonction : Auteur
Patricia Sierra
  • Fonction : Auteur
Pedro Izquierdo-Bueno Martin
  • Fonction : Auteur
Agustín Albillos
Marco Domenicali
  • Fonction : Auteur
Christian Jansen
  • Fonction : Auteur
Wenyi Gu
  • Fonction : Auteur
Maria Papp
  • Fonction : Auteur
Raj Mookerjee
  • Fonction : Auteur
Carmine Gabriele Gambino
Cesar Jiménez
Ilaria Giovo
  • Fonction : Auteur
Giacomo Zaccherini
Manuela Merli
  • Fonction : Auteur
Antonella Putignano
  • Fonction : Auteur
Frank Erhard Uschner
  • Fonction : Auteur
Thomas Berg
Tony Bruns
Christian Trautwein
Alexander Zipprich
Rafael Bañares
  • Fonction : Auteur
José Presa
  • Fonction : Auteur
Joan Genesca
  • Fonction : Auteur
Victor Vargas
  • Fonction : Auteur
Javier Fernández
  • Fonction : Auteur
Mauro Bernardi
Paolo Angeli
Rajiv Jalan
  • Fonction : Auteur
Joan Claria
Christophe Junot
  • Fonction : Auteur
Richard Moreau
Jonel Trebicka
Vicente Arroyo
  • Fonction : Auteur

Résumé

Background and aims Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes, which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models. Methods Two prospective multicentre large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT (validation, n=851), were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling. Results Three prognostic metabolites strongly associated with death were selected to build the models. 4-Hydroxy-3-methoxyphenylglycol sulfate is a norepinephrine derivative, which may be derived from the brainstem response to SI. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulfate, hexanoylcarnitine, bilirubin, international normalised ratio (INR) and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared with MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.940, 0.834 and 0.791, and 0.947, 0.857 and 0.810, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa 7, 14 and 28 days after admission for prediction of mortality. Conclusions Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (eg, MELDNa), especially in patients with ACLF.

Dates et versions

hal-04403488 , version 1 (18-01-2024)

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Citer

Emmanuel Weiss, Carlos de la Peña-Ramirez, Ferran Aguilar, Juan-Jose Lozano, Cristina Sánchez-Garrido, et al.. Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET). Gut, 2023, 72 (8), pp.1581-1591. ⟨10.1136/gutjnl-2022-328708⟩. ⟨hal-04403488⟩
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