Relationship Of Hepatitis B Virus X Protein Expression With Hepatic Steatosis And Its Possible Mechanism

Background and aims: Hepatitis B virus (HBV) infection is a serious public health problem with more than 350 million people being chronic carriers of the virus worldwide. About one million people die from liver failure,cirrhosis and primary liver cancer caused by HBV infection each year. Hepatic steatosis is the hallmark of NAFLD, which includes a spectrum of disorders from simple steatosis to steatohepatitis, fibrosis and the development of cirrhosis. It is also a common histological feature of chronic hepatitis B. The frequency of steatosis in HBV infection ranges from27% to 51%, which is much higher than the general population. However, whether HBV infection itself could increase the risk of hepatic steatosis in the same way as HCV infection remains largely unknown. In this study we show the molecular mechanism by which hepatitis B virus X protein (HBx) induces hepatic steatosis.Methods Thirty-six patients classified as (1)18 patients with CHB; (2) and 18 with CHB accompanied by fatty liver were enrolled in this study. Demographic and laboratory data including gender,sex,plasma levels of TG,CHOL,ALT,AST,fasting glucose and HBV DNA load from 36 patients were obtained and analyzed.HBsAg,HBcAg,HBx,LXRαand FAS were detected in paraffin embedded liver biopsies from 36 patients by immunohistochemistry. Hepatic lipid accumulation in HepG2.2.15 and HepG2 cells were observed by oil red O staining. The expression of HBx, LXRαand FAS in cells were investigated by western blot.Results No significant difference was found in gender (P=0.22),sex (P=0.35),plasma TG (P=0.89),CHOL(P=0.62),ALT (P=0.96),AST(P=0.60),fasting glucose(5.30±0.40 vs5.50±0.35,P>0.05),HBV DNA load (P=0.79),the grade of inflammation (P=0.96) and the stage of fibrosis (P=0.98),the expression of HBsAg and HBcAg in liver tissues(P>0.05) between two groups. However,in the group of CHB accompanied by fatty liver and HepG2.2.15 cells, the expression of HBx,LXRαand FAS was significantly higher than those in the group of CHB and HepG2 cells,respectively(P<0.05),which was in accordance with the level of hepatic steatosis.Conclusions It is suggested that HBx interacts with LXRα, thereby resulting in the up-regulation of FAS which could be a putative molecular mechanism of fatty liver.