The term cirrhosis-associated immune dysfunction refers to the
main syndromic abnormalities of immune function, immunodefi-
ciency and systemic inflammation that are present in cirrhosis.
The course of advanced cirrhosis, regardless of its aetiology, is complicated
by cirrhosis-associated immune dysfunction and this constitutes
the pathophysiological hallmark of an increased
susceptibility to bacterial infection, distinctive of the disease.
Cirrhosis impairs the homeostatic role of the liver in the systemic
immune response. Damage to the reticulo-endothelial system compromises
the immune surveillance function of the organ and the
reduced hepatic synthesis of proteins, involved in innate immunity
and pattern recognition, hinders the bactericidal ability of phagocytic
cells. Systemic inflammation, in form of activated circulating
immune cells and increased serum levels of pro-inflammatory cytokines,
is the result of persistent episodic activation of circulating
immune cells from damage-associated molecular patterns, released
from necrotic liver cells and, as cirrhosis progresses, from pathogenassociated
molecular patterns, released from the leaky gut.
Cirrhosis-associated immune dysfunction phenotypes switch from
predominantly ‘‘pro-inflammatory’’ to predominantly ‘‘immunode-
ficient’’ in patients with stable ascitic cirrhosis and in patients with
severely decompensated cirrhosis and extra-hepatic organ failure
(e.g. acute-on-chronic liver failure), respectively. These cirrhosisassociated
immune dysfunction phenotypes represent the
extremes of a spectrum of reversible dynamic events that take
place during the course of cirrhosis. Systemic inflammation can