Role of inflammation and infection in the pathogenesis of human acute liver failure: Clinical implications for monitoring and therapy

Table 1 Cell types and proteins involved in immune pathogenesis of acute liver failure

Ref.	Cell type/protein study population	Finding in ALF
Taylor et al[12]	Neutrophils	Significant reduction in neutrophil surface expression of CD16 (causing reduced binding capacity) and neutrophil phagocytic activity compared with healthy controls. Impaired phagocytic activity predictive of death without transplantation
	ALF
Manakkat Vijay et al[13]	Neutrophils	Toll-like receptors sense pathogens and induce inflammatory responses. Neutrophil toll-like receptor 9 expression increased on day 1 compared with healthy controls, and correlated with severity of HE and SIRS
	APAP-ALF
Srungaram et al[14]	Osteopontin (activates neutrophils and macrophages)	Median osteopontin levels significantly elevated in the ALF group compared with comparator cohorts; median osteopontin levels were highest in patients with APAP-ALF and ischaemic hepatitis (conditions associated with a hyperacute course and better outcomes - osteopontin may have a central role to play in the resolution of ALF)
ALFSG	ALF
Lawson et al[15]	Neutrophils	Neutrophils accumulate in liver parallel to or slightly after liver injury; number of neutrophils in liver substantial compared with baseline, with increased levels of TNF-α, KC and MIP-2 chemokines
	APAP-ALF
Sehgal et al[16]	Monocyte-macrophages	Functionality of monocytes and macrophages impaired in pregnant patients developing ALF compared with those with ALI.
	Hepatitis E in Pregnancy
Wigmore et al[17]	Monocytes	Peripheral blood mononuclear cells from patients with ALF show reduced potential to produce IL-6 and TNF and elicit an acute phase response in vitro
	ALF
Leifeld et al[18]	Macrophages	CC-chemokines recruit and activate macrophages and T-cells. Elevated levels of serum and intrahepatic chemokines in ALF compared with controls, correlating with extent of infiltration by macrophages and T-cells.
	ALF
dos Santos et al[19]	Eosinophils	High number of intrahepatic eosinophils in ALF, associated with increased expression of IL-6.
	ALF
Wyke et al[20]	Complement system	Defective opsonisation due to complement deficiency. Complement factors reduced to below 40% of the activity of control serum
	ALF

ALF: Acute liver failure; APAP: Acetaminophen; SIRS: Systemic inflammatory response.