Table 2.

Evidence for the role of LPS/TLR4 signaling in chronic hepatic diseases

Disease	LPS expression	TLR4 expression	TLR4 sensitivity	Effects of modulation of TLR4	Cellular and intracellular pathways
Alcoholic liver disease	↑ [24–26]	↑ [29]	↑ [29, 30]	Suppression of TLR4 protects against ALD [30–32]	KC, Myd88-independent, TNF-α and IL-6 and ROS [34, 35]
Non-alcoholic fatty liver disease	↑ [37–41]	↑ [42]	↑ [42]	Suppression of TLR4 protects against NAFLD [39–41, 43–45]	KC, Myd88-dependent, TNF-α and IL-6 and ROS [39, 45]
HCV infection	↑ [49]	↑ (in B cells and hepatocytes) [22, 50] ↑ (in DC and macrophages) [51, 52]	↑ (in B cells and hepatocytes) [22, 50] ↓ (DC and macrophages) [51, 52]	Activation of TLR4 suppresses HCV replication [53]	KC and LSEC, Myd88-independent, IFN-β [53]
HBV infection	↑ [56]	↓ [57]	↓ [57]	Activation of TLR4 suppresses HBV replication [58]	KC, Myd88-independent, IFN-β [59]
Primary biliary cirrhosis	↑ (in BEC) [60, 61]	↑ (in BEC) [62]	↑ [63]	nd	BEC, TNF-α, IL-1 [63]
Primary sclerosing cholangitis	↑ (in BEC) [60]	↑ (in BEC) [64]	↑ [64]	nd	BEC, TNF-α, IL-1 [64]
Hepatic fibrosis	↑ [21, 67]	BEC ↑ [62, 64] Hepatocytes ↑/= [62, 69] PBMC ↓/= [70, 71]	BEC ↑ [62, 64] Hepatocytes ↑/= [62, 69] PBMC ↓/= [70, 71]	Suppression of TLR4 protects against hepatic fibrosis [21, 55, 72–76]	HSC, Myd88-dependent, Chemokines, adhesion molecules, BAMBI [21]
Hepatocarcinoma	↑ [22]	↑ [22]	↑ [22]	Suppression of TLR4 protects against hepatocarcinoma [12, 22]	KC and hepatocytes, Myd88-dependent, Nanog; IL-6 [12, 22]

↑ increased, ↓ decreased, = maintained, LPS lipopolysaccharide, BEC biliary epithelial cells, DC dendritic cells, KC Kupffer cells, LSEC liver sinusoidal endothelial cells, PBMC peripheral blood mononuclear cells, ROS reactive oxygen species, nd not determined