Cristina López-Vicario1, Antonio Checa2, Arantxa Urdangarin3, Ferran Aguilar4, José Alcaraz-Quiles5, Paolo Caraceni6, Alex Amorós4, Marco Pavesi4, David Gómez-Cabrero3, Jonel Trebicka7, Karl Oettl8, Richard Moreau9, Núria Planell3, Vicente Arroyo4, Craig E Wheelock2, Joan Clària10. 1. European Foundation for the Study of Chronic Liver Failure (EF-Clif) and Grifols Chair, Barcelona, Spain; Biochemistry and Molecular Genetics Service, Hospital Clínic-IDIBAPS and CIBERehd, Barcelona, Spain. 2. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. 3. Translational Bioinformatics Unit, NavarraBiomed, Pamplona, Spain. 4. European Foundation for the Study of Chronic Liver Failure (EF-Clif) and Grifols Chair, Barcelona, Spain. 5. Biochemistry and Molecular Genetics Service, Hospital Clínic-IDIBAPS and CIBERehd, Barcelona, Spain. 6. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. 7. European Foundation for the Study of Chronic Liver Failure (EF-Clif) and Grifols Chair, Barcelona, Spain; J.W. Goethe University Hospital, Frankfurt, Germany. 8. Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria. 9. European Foundation for the Study of Chronic Liver Failure (EF-Clif) and Grifols Chair, Barcelona, Spain; Inserm, U1149, Centre de Recherche sur l'Inflammation (CRI), UMRS1149; Université Paris Diderot-Paris 7, Paris, France. 10. European Foundation for the Study of Chronic Liver Failure (EF-Clif) and Grifols Chair, Barcelona, Spain; Biochemistry and Molecular Genetics Service, Hospital Clínic-IDIBAPS and CIBERehd, Barcelona, Spain; Department of Biomedical Sciences, University of Barcelona, Barcelona, Spain. Electronic address: jclaria@clinic.cat.
Abstract
BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a newly described syndrome, which develops in patients with acute decompensation of cirrhosis, and is characterized by intense systemic inflammation, multiple organ failures and high short-term mortality. The profile of circulating lipid mediators, which are endogenous signaling molecules that play a major role in inflammation and immunity, is poorly characterized in ACLF. METHODS: In the current study, we assessed the profile of lipid mediators by liquid chromatography coupled to tandem mass spectrometry in plasma from patients with acute decompensation of cirrhosis, with (n = 119) and without (n = 127) ACLF, and from healthy controls (n = 18). Measurements were prospectively repeated in 191 patients with acute decompensation of cirrhosis during a 28-day follow-up period. RESULTS: Fifty-nine lipid mediators (out of 100) were detected in plasma from cirrhotic patients, of which 16 were significantly associated with disease status. Among these, 11 lipid mediators distinguished patients at any stage from healthy controls, whereas 2 lipid mediators (LTE4 and 12-HHT, both derived from arachidonic acid) shaped a minimal plasma fingerprint that discriminated patients with ACLF from those without. Levels of LTE4 distinguished ACLF grade 3 from ACLF grades 1 and 2, followed the clinical course of the disease (increased with worsening and decreased with improvement) and positively correlated with markers of inflammation and non-apoptotic cell death. Moreover, LTE4 together with LXA5 (derived from eicosapentaenoic acid) and EKODE (derived from linoleic acid) were associated with short-term mortality. LXA5 and EKODE formed a signature associated with coagulation and liver failures. CONCLUSION: Taken together, these findings uncover specific lipid mediator profiles associated with disease severity and prognosis in patients with acute decompensation of cirrhosis. LAY SUMMARY: Acute-on-chronic liver failure (ACLF) is characterized by intense systemic inflammation, multiple organ failures and high short-term mortality. In the current study, we assessed the plasma lipid profile of 100 bioactive lipid mediators in healthy controls, patients with decompensated cirrhosis, and those who had developed ACLF. We identified lipid mediator signatures associated with inflammation and non-apoptotic cell death that discriminate disease severity and evolution, short-term mortality and organ failures.
BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a newly described syndrome, which develops in patients with acute decompensation of cirrhosis, and is characterized by intense systemic inflammation, multiple organ failures and high short-term mortality. The profile of circulating lipid mediators, which are endogenous signaling molecules that play a major role in inflammation and immunity, is poorly characterized in ACLF. METHODS: In the current study, we assessed the profile of lipid mediators by liquid chromatography coupled to tandem mass spectrometry in plasma from patients with acute decompensation of cirrhosis, with (n = 119) and without (n = 127) ACLF, and from healthy controls (n = 18). Measurements were prospectively repeated in 191 patients with acute decompensation of cirrhosis during a 28-day follow-up period. RESULTS: Fifty-nine lipid mediators (out of 100) were detected in plasma from cirrhotic patients, of which 16 were significantly associated with disease status. Among these, 11 lipid mediators distinguished patients at any stage from healthy controls, whereas 2 lipid mediators (LTE4 and 12-HHT, both derived from arachidonic acid) shaped a minimal plasma fingerprint that discriminated patients with ACLF from those without. Levels of LTE4 distinguished ACLF grade 3 from ACLF grades 1 and 2, followed the clinical course of the disease (increased with worsening and decreased with improvement) and positively correlated with markers of inflammation and non-apoptotic cell death. Moreover, LTE4 together with LXA5 (derived from eicosapentaenoic acid) and EKODE (derived from linoleic acid) were associated with short-term mortality. LXA5 and EKODE formed a signature associated with coagulation and liver failures. CONCLUSION: Taken together, these findings uncover specific lipid mediator profiles associated with disease severity and prognosis in patients with acute decompensation of cirrhosis. LAY SUMMARY: Acute-on-chronic liver failure (ACLF) is characterized by intense systemic inflammation, multiple organ failures and high short-term mortality. In the current study, we assessed the plasma lipid profile of 100 bioactive lipid mediators in healthy controls, patients with decompensated cirrhosis, and those who had developed ACLF. We identified lipid mediator signatures associated with inflammation and non-apoptotic cell death that discriminate disease severity and evolution, short-term mortality and organ failures.
Authors: Florent Artru; Mark J W McPhail; Evangelos Triantafyllou; Francesca Maria Trovato Journal: Front Immunol Date: 2022-03-31 Impact factor: 7.561
Authors: Isabel Graupera; Laura Isus; Mar Coll; Elisa Pose; Alba Díaz; Julia Vallverdú; Teresa Rubio-Tomás; Celia Martínez-Sánchez; Patricia Huelin; Marta Llopis; Cristina Solé; Constantino Fondevila; Juan José Lozano; Pau Sancho-Bru; Pere Ginès; Patrick Aloy Journal: JHEP Rep Date: 2022-04-04
Authors: Mireia Casulleras; Roger Flores-Costa; Marta Duran-Güell; Ingrid W Zhang; Cristina López-Vicario; Anna Curto; Javier Fernández; Vicente Arroyo; Joan Clària Journal: Hepatol Commun Date: 2022-02-18