Inverse correlation between plasma oxysterol and LDL-cholesterol levels in hepatitis C virus-infected patients

Background: Hepatitis C virus infection is characterised by enhanced oxidative stress, which can be measured quantitatively by plasma oxysterol concentration. These molecules may affect lipid metabolism through the activation of Liver X Receptors. Hepatitis C virus exploits host lipid metabolism to facilitate its replication and diffusion. In our study we aimed to evaluate and highlight the potential pathogenetic role of oxysterols, 7-ketocholesterol and 7-β-hydroxycholesterol, in hepatitis C virus-related lipid dysmetabolism. Methods: The study was performed in 42 patients with chronic hepatitis C (93% genotype 1b) and 38 non-alcoholic fatty liver disease patients. Plasma oxysterols 7-ketocholesterol and 7-β-hydroxycholesterol were determined by isotope dilution gas chromatography/mass spectrometry. Results: Gas chromatography/mass spectrometry revealed higher 7-ketocholesterol (71.2 ± 77.3 vs 30.4 ± 14.5; p<0.005) and 7-β-hydroxycholesterol (23.7 ± 20.6 vs 11.5 ± 4.9; p<0.001) plasma levels in hepatitis C virus patients. Furthermore, multivariate regression analysis highlighted an inverse independent correlation between high oxysterol levels and low low-density lipoprotein cholesterol (p=0.01 for 7-β-hydroxycholesterol; p=0.02 for 7-ketocholesterol) in the hepatitis C virus group; in contrast, the non-alcoholic fatty liver disease group showed a direct correlation between oxysterol levels and low-density lipoprotein-cholesterol (p<0.001 for 7-β-hydroxycholesterol; p=0.002 for 7-ketocholesterol). Conclusion: These different correlations reveal profound differences in lipid dysmetabolism between chronic hepatitis C and non-alcoholic fatty liver disease patients