Figure 2

Possible mechanisms of non-viral and viral steatosis. (A) In NAFLD/NASH, subjects are insulin resistant and have high plasma free fatty acids (FFA). High FFA delivery to the liver enhances lipoprotein production. Presence of MTP -493G allele, which associates with lower MTP transcription, may lead to impairments of VLDL secretion and consequently to severe intrahepatic lipid accumulation. (B) In HCV infected individuals MTP mRNA and protein levels could be a consequence of up/down-regulation of either suppressors or activators of MTP expression by HCV. During early stages of infection MTP transcriptional activity might be enhanced to facilitate assembly and secretion of infectious HCV-particles (i). At a later stage of infection (ii), HCV may decrease MTP expression through an up-regulation of some MTP suppressors. This suppressor might decrease MTP expression. In addition, this suppressor may increase lipogenesis leading to lipid accumulation and hepatic steatosis. In the presence of T allele at -493 site, decrease in MTP mRNA levels may occur either through a direct binding of some HCV proteins at the -493 site or through an up-regulation of MTP-suppressor(s) by HCV thus contrasting the enhancing effect of the T allele on MTP gene expression. We speculate that increased lipid droplets accumulation in hepatocytes may provide a safe environment for HCV latency.