Javier Fernández1, Joan Clària2, Alex Amorós3, Ferrán Aguilar3, Miriam Castro4, Mireia Casulleras4, Juan Acevedo5, Marta Duran-Güell4, Laura Nuñez6, Montserrat Costa6, Mireia Torres6, Raquel Horrillo6, Luis Ruiz-Del-Árbol7, Cándido Villanueva8, Verónica Prado4, Mireya Arteaga4, Jonel Trebicka9, Paolo Angeli10, Manuela Merli11, Carlo Alessandria12, Niels Kristian Aagaard13, German Soriano14, François Durand15, Alexander Gerbes16, Thierry Gustot17, Tania M Welzel18, Francesco Salerno19, Rafael Bañares20, Victor Vargas21, Agustin Albillos7, Aníbal Silva4, Manuel Morales-Ruiz4, Juan Carlos García-Pagán4, Marco Pavesi3, Rajiv Jalan22, Mauro Bernardi23, Richard Moreau24, Antonio Páez6, Vicente Arroyo3. 1. EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain. Electronic address: javier.fernandez@efclif.com. 2. EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain. 3. EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain. 4. Hospital Clínic, IDIBAPS and CIBERehd, Barcelona, Spain. 5. South West Liver Unit, Derriford Hospital, Plymouth, United Kingdom. 6. Bioscience Research Group, Grifols, Barcelona, Spain. 7. Department of Gastroenterology, Hospital Ramón y Cajal and CIBERehd, Madrid, Spain. 8. Department of Gastroenterology, Hospital de Sant Pau and CIBERehd, Barcelona, Spain. 9. EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Department of Internal Medicine, University Hospital of Bonn, Bonn, Germany. 10. EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Unit of Internal Medicine and Hepatology, Department of Medicine, DIMED, University of Padova, Padova, Italy. 11. Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy. 12. Division of Gastroenterology and Hepatology, San Giovanni Battista Hospital, Torino, Italy. 13. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. 14. Department of Gastroenterology and Hepatology, Hospital of Santa Creu i Sant Pau and CIBERehd, Barcelona, Spain. 15. Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. 16. Department of Medicine II, Liver Centre Munich, University Hospital, LMU Munich, Munich, Germany. 17. Liver Transplant Unit, Erasme Hospital (ULB), Brussels, Belgium. 18. Medical Department I, Goethe University, Frankfurt, Germany. 19. Department of Internal Medicine, Policlinico IRCCS San Donato, Milano, Italy. 20. Department of Gastroenterology, Hospital Gregorio Marañon, and CIBERehd, Madrid, Spain. 21. Department of Internal Medicine, Hospital Vall d'Hebron and CIBERehd, Barcelona, Spain. 22. Liver Failure Group, Institute for Liver Disease Health, University College London, Royal Free Hospital, London, United Kingdom. 23. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. 24. EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; Inserm, Université Paris Diderot-Paris 7, Centre de Recherche sur l'Inflammation, Paris, France.
Abstract
BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS:Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.
RCT Entities:
BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS:Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.
Authors: Manuel Tufoni; Giacomo Zaccherini; Paolo Caraceni; Mauro Bernardi Journal: United European Gastroenterol J Date: 2020-02-26 Impact factor: 4.623
Authors: Nikolaus Pfisterer; Caroline Schmidbauer; Florian Riedl; Andreas Maieron; Vanessa Stadlbauer; Barbara Hennlich; Remy Schwarzer; Andreas Puespoek; Theresa Bucsics; Maria Effenberger; Simona Bota; Michael Gschwantler; Markus Peck-Radosavljevic; Mattias Mandorfer; Christian Madl; Michael Trauner; Thomas Reiberger Journal: Wien Klin Wochenschr Date: 2020-12-03 Impact factor: 1.704