February 28, 2022 How alteration in the composition of albumin-associated lipids in acute decompensation of cirrhosis impairs resolution of inflammation New research investigates the changes in fatty acids bound to plasma albumin and its implications in the production of inflammatory and immunosuppressive lipid mediators in advanced liver disease

BARCELONA—Albumin administration has been proven to be an effective therapy for patients with acute decompensation of cirrhosis. Albumin, the most abundant protein in the bloodstream, is synthesized by the liver and its high affinity for fatty acids allows for the transport of lipids that serve as substrates for the synthesis of membrane phospholipids and some bioactive compounds. In advanced liver disease, post-translational modifications of albumin may result in changes in its lipid content and thus alter the circulating lipid profile.

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From left: Mireia Casulleras and Joan Clària, PhD

Credit: Mireia Casulleras (left), EF Clif (right)

Researchers at the European Foundation for the Study of Chronic Liver Failure (EF Clif) studying cirrhotic patients admitted to the Liver Intensive Care Unit at Hospital Clínic de Barcelona, Spain, have now described alterations on the plasma profile of lipid mediators derived from polyunsaturated fatty acids in patients with acute decompensation of cirrhosis compared to healthy subjects.

This new study published on 18 February 2022 in Hepatology Communications reveals that the overall plasma concentration of lipid mediators is reduced in patients with advanced liver disease and suggests that albumin modulates the release of lipid mediators by peripheral leukocytes promoting resolution of inflammation, a process that may be impaired in acute decompensation of cirrhosis. “We found that circulating albumin has a distinct lipid composition characterized by a profound depletion in the content of anti-inflammatory lipid mediators in patients with advanced cirrhosis compared to that of healthy subjects”, said Mireia Casulleras, leading author on the paper and pre-doctoral researcher at the Inflammation and Hepatic Diseases group at Hospital Clínic de Barcelona-August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Spain.

The study also examined the levels of lipid mediators in plasma in patients with acute decompensation of cirrhosis from a previous albumin clinical trial. Sort-term albumin treatment in these patients resulted in a reduction of prostaglandin E2, a lipid mediator that drives immunosuppression, and an increase of 15-hydroxyeicosatetraenoic acid (15-HETE), an intermediate marker of the biosynthesis of pro-resolving lipid mediators. “These findings might contribute to understand the anti-inflammatory effects observed during albumin infusions in patients with acute decompensation of cirrhosis”, said Joan Clària, corresponding author of the paper, Director of the Grifols Chair and head of translational operations at EF Clif and principal investigator at Hospital Clínic de Barcelona-IDIBAPS, Spain. Despite the preliminary nature of these results, these findings suggest a role for albumin as a modulator of the biosynthesis of bioactive lipid mediators and release by circulating immune cells.

This study was supported by the Agency for Management of University and Research Grants of the Government of Catalonia grant 2017SGR1449 and the Spanish Ministry of Science and Innovation grant PID2019-105240RB-I00.

Other authors on the study are Roger Flores-Costa, Marta Duran-Güell, Ingrid W. Zhang, Cristina López-Vicario, Anna Curto, Javier Fernández, and Vicente Arroyo.

Publication information

Casulleras, M.; Flores-Costa, R.; Duran-Güell, M.; Zhang, I. W.; López-Vicario, C.; Curto, A.; Fernández, J.; Arroyo, V.; Clària, J. Albumin lipidomics reveals meaningful compositional changes in advanced cirrhosis and its potential to promote inflammation resolution. Hepatol. Commun. 2022. DOI: 10.1002/hep4.1893

The European Foundation for the Study of Chronic Liver Failure (EF Clif) is a private nonprofit organization which mission is to promote research and education in hepatic chronic failure with the aim to contribute to improving the quality of life and to increase the survival of patients with liver cirrhosis. Since its foundation in 2009, the European Association for the Study of the Liver (EASL) Chair supports research activities through the EASL-Clif Consortium, a network of more than 100 European university hospitals and more than 300 clinical researchers. The Grifols Chair promotes translational studies across centers throughout Europe and North America within the framework of the European Network for Translational Research (ENTR) with 25 centers and more than 40 investigators.