The continuous activation of TLR4 signaling in B cells from the portal hypertension-induced enhancement of gut permeability, leads to a B cell exhaustion phenotype [43], while blockage of TLR4 in 3T3-L1 cells leads to a significant reduction in IL-6 production upon stimulation with HCV core protein, with potentially beneficial effects in liver steatosis and insulin resistance [44]. Here, TLR4 is linked to portal hypertension.