Fig. 2.

The immunopathological landscape in peripheral blood of patients with acutely decompensated cirrhosis and ACLF is characterised by neutrophilia and severe lymphopenia.

The monocyte population can be slightly increased or within the normal range. In addition to increased neutrophil counts, patients with acute-on-chronic liver failure (ACLF) exhibit an augmented number of immature neutrophil precursors, indicating enhanced emergency granulopoiesis. Blood neutrophils from patients with ACLF also show signs of hyperactivation, increased CD177 expression and adhesion to endothelium. Paradoxically, in this hyperinflammatory environment, the bactericidal activities of neutrophils are impaired. All these neutrophil activities are nurtured through a very intense glycolytic metabolism. The blood monocytes circulating in patients with ACLF also present reduced antigen presentation, HLA-DR expression and antibacterial function. Despite the number of monocytes not being decreased, patients with ACLF exhibit reduced numbers of CD14+CD16- (classical) and CD14+CD16+ (intermediate) monocytes. Also, a higher number of MerTK+ (immunosuppressed) monocytes is observed in this condition. On the other hand, in addition to decreased lymphocyte counts, mainly affecting CD4+ and CD8+ T lymphocytes, and memory B cells, patients with ACLF exhibit impaired lymphocyte function. The increased neutrophil to lymphocyte ratio and the above-described features set the ground for the presence of a concomitant hyperinflammatory and defective host defences in the peripheral blood of patients with acutely decompensated cirrhosis and ACLF.