Cell surface expression of LDL receptor in chronic hepatitis C: correlation with viral load.

The LDL receptor (LDL-R) has been proposed as the viral receptor for Hepatitis C virus (HCV). This hypothesis has been based exclusively on in vitro studies. In human mononuclear cells, LDL-R gene expression has been demonstrated to be parallel and be coordinately regulated to gene expression in the human liver. The purpose of the current study was to determine the mononuclear cell surface expression of the LDL receptor in patients with HCV chronic infection according to viral load. Sixty-eight consecutive untreated chronic hepatitis C patients were studied to determine the mononuclear cell surface expression of the LDL-R. LDL-Rs were quantified at the surface of mononuclear cells in fresh blood samples taken after fasting using flow cytometry. LDL-R expression was significantly associated with LDL-cholesterol (r = -0.25; P = 0.03) and HCV-viral load (r = 0.37, P = 0.002). In multivariate analysis, the LDL-R expression was significantly associated with HCV viral load, whereas genotype, age, body mass index, and fibrosis were not. In conclusion, our data provided by a human study, suggest that the LDL-R may be one of the receptors implicated in HCV replication.

Apolipoprotein-AII concentrations are associated with liver steatosis in patients with chronic hepatitis C.

It has been shown that the hepatitis C virus (HCV) core protein reduces the activity of the microsomal triglyceride transfer protein (MTP) and could lead to steatosis in HCV-infected patients. Experimentally, apolipoprotein-AII (apoAII), which restores triglyceride secretion altered by the HCV core protein, could be protective against HCV steatosis. On the other hand, increasing plasma concentrations of mouse apoAII in transgenic mice produced several aspects of insulin-resistance syndrome, which also is implicated in the pathogenesis of HCV steatosis. This study was designed to investigate the role of apoAII in HCV-related steatosis in humans. Sixty-five hospitalized patients with chronic HCV were included in this study to assess the effects of apoAII, body mass index (BMI), age, insulin sensibility (HOMA), and leptin level on steatosis. Steatosis was observed in 55.3% of patients. Apo-AII was significantly associated with HOMA and with leptin concentrations. In univariate analyses, age, BMI, increased leptin level, increased HOMA, and increased apoAII concentration were associated with steatosis. In multivariate analysis, steatosis was associated with apoAII concentration, age, gender, and BMI. Contrary to previous hypotheses, apoAII is not a protective factor against HCV steatosis but is significantly associated with the development of liver steatosis. The fact that the plasma levels of apoAII correlate with HOMA and leptin levels in HCV-infected patients suggests that apoAII may contribute to hepatic steatosis progression in relationship to visceral obesity, insulin resistance, and metabolism of triglyceride-rich lipoproteins.