1A). SHP, CAR, and NCOA3 mRNA levels were increased in HCV-infected patients in comparison with normal controls. Hepatic RXRα, PPARα, and PPARβ mRNA levels were decreased in HCV-infected patients compared with normal controls. There was no change in the expression levels of other nuclear receptors including FXR (Supporting Fig. 1A). The expression of genes (Supporting Table 1) that play pivotal roles in regulating lipid homeostasis was studied. The mRNA level of

steroid Ponatinib molecular weight regulatory element-binding protein (SREBP)-1c was decreased in HCV-infected livers (Fig. 1B). The expression levels of SREBP-1c target genes (fatty acid synthase [FAS], acyl-CoA carboxylase [ACC], and fatty acyl-CoA elongase [FAE]) were modestly reduced in HCV-infected livers, but did not reach statistical significance (Supporting Fig. 1B). Genes responsible for fatty acid uptake (fatty acid transport protein 2 and 5 [FATP2 and FATP5]) and glucose uptake (facilitated glucose transporter 2 [GLUT2]) were up-regulated in HCV-infected livers (Fig. 1B). The expression of low-density lipoprotein receptor (LDLR), which plays a key role in viral entry to the hepatocyte,22 Alvelestat was decreased by four-fold

in HCV-infected patients (Fig. 1B). In addition, the mRNA levels of microsomal triglyceride transfer protein (MTP), which is essential for very low-density lipoprotein (VLDL) and HCV secretion from the infected cells,23 was increased in HCV-infected livers (Fig. 1B). Cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1) catalyzes a rate-limiting step in cholesterol catabolism and bile acid biosynthesis. Na+/taurocholate cotransporter (NTCP) controls the uptake of bile acid. The expression levels

of both genes were increased in HCV-infected livers (Fig. 1C). The mRNA level of CYP7A1 increased more than 13-fold. CYP7A1 and NTCP are negatively regulated by SHP. However, HCV-infected patients have increased CYP7A1 and NTCP as well as SHP mRNA levels. Inflammatory pathway gene expression was altered in HCV-infected livers (Fig. 1D). HCV-infected patients had increased expression of tumor necrosis factor α (TNF; three-fold) and nitric oxide synthase 2 (NOS2; seven-fold). The expression of genes in the fatty selleck compound acid oxidation pathway and antioxidant system showed no significant difference (Supporting Fig. 1C,D). There is a sex difference in alcohol intake and alcoholic liver disease; female sex is a protective factor for drinking and yet female individuals are more susceptible than male individuals to the development of alcoholic liver disease.19 It is essential to use sex-matched populations to study biomarkers for alcohol use. Thus, we compared gene expression patterns between HCV-infected men with and without an alcohol drinking history.