Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep32341
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Funding
- Fondos de Investigacion de Salud Carlos III in the Plan Nacional I + D + I [PI12/00330]
- ISCIII-Subdireccion General de Evaluacion
- European Regional Development Fund FEDER
- Instituto de Salud Carlos III (PFIS fellowship) [FI14/00227]
- Plan Estatal I + D + I
- Instituto Carlos III (Rio-Hortega fellowship) [CM14/00122]
- University of Barcelona (APIF)
- ICREA Academia Award
- AGAUR (Agencia de Gestio d'Ajuts Universitaris I de Recerca) Award [2014/SGR 708]
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ACLF is characterized by a systemic inflammatory response, but the cytokines involved in this process have not been well studied. The aim of this study was to characterize the systemic inflammatory response in patients with cirrhosis and ACLF and its relationship with prognosis. Fifty-five patients with cirrhosis, 26 with ACLF, were studied prospectively. Systemic inflammatory response was analyzed by measuring a large array of plasma cytokines by using a multiplex kit. A principal component analysis show noticeable differences between ACLF and decompensated cirrhosis without ACLF. Patients with ACLF had significant abnormal levels of 12 cytokines compared to those without ACLF, including: VCAM-1, VEGF-A, Fractalkine, MIP-1 alpha, Eotaxin, IP-10, RANTES, GM-CSF, IL-1 beta, IL-2, ICAM-1, and MCP-1. Cytokines showing the most marked relationship with ACLF were VCAM-1 and VEGF-A (AUCROC 0.77; p = 0.001). There was a significant relationship between some of inflammatory mediators and 3-month mortality, particularly VCAM-1, ICAM-1, and GM-CSF (AUCROC>0.7; p < 0.05). Functional Enrichment Analysis showed that inflammatory markers differentially expressed in ACLF patients were enriched in leukocyte migration, particularly monocytes and macrophages, and chemotaxis pathways. In conclusion, ACLF is characterized by a marked inflammatory reaction with activation of mediators of adhesion and migration of leukocytes. The intensity of the inflammatory reaction correlates with prognosis.
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