Characterization of Inflammatory Response in Acute-on-Chronic Liver Failure and Relationship with Prognosis

Abstract

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-1α, Eotaxin, IP-10, RANTES, GM-CSF, IL-1β, 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.

Persistently Increased Resting Energy Expenditure Predicts Short-Term Mortality in Patients with Acute-on-Chronic Liver Failure

“…Hypermetabolism reflects systemic inflammation response in patients with advanced cirrhosis. Systemic inflammation response is an important risk factor for acute liver failure and ACLF outcome [28, 29]. In addition, in our study, BMI and FFM positively correlated with CRP.…”

Pro: Acute‐on‐chronic liver failure

“…Results from both studies show that patients with ACLF have markedly increased levels of circulating proinflammatory cytokines and chemokines (ie, IL6, IL8, tumor necrosis factor α, monocyte chemoattractant protein 1, vascular cell adhesion molecule 1, vascular endothelial growth factor A) compared with patients with acute decompensation without ACLF . Interestingly, these cytokines impaired in ACLF syndrome are mainly related to chemotaxis and migration of leukocytes, particularly monocytes, and macrophages . Results of these studies show that although patients with decompensated cirrhosis already present increased circulating cytokines, plasma cytokine levels are markedly enhanced in patients with ACLF.…”

“…Two recently published studies investigated the circulating cytokine profile in patients with decompensated cirrhosis with and without ACLF and showed similar findings. Results from both studies show that patients with ACLF have markedly increased levels of circulating proinflammatory cytokines and chemokines (ie, IL6, IL8, tumor necrosis factor α, monocyte chemoattractant protein 1, vascular cell adhesion molecule 1, vascular endothelial growth factor A) compared with patients with acute decompensation without ACLF . Interestingly, these cytokines impaired in ACLF syndrome are mainly related to chemotaxis and migration of leukocytes, particularly monocytes, and macrophages .…”

“…Results of these studies show that although patients with decompensated cirrhosis already present increased circulating cytokines, plasma cytokine levels are markedly enhanced in patients with ACLF. Moreover, levels of some proinflammatory cytokines (ie, IL6, IL8, and intercellular cell adhesion molecule 1) were associated with the clinical course of ACLF, the number of organ failures, and mortality …”

“…Besides an excessive systemic inflammation, patients with ACLF also show a marked increase of anti‐inflammatory cytokines, such as IL10 and IL1Ra . These findings suggest the existence of a compensatory immune response that would not be enough to mitigate the excessive inflammation.…”