493 METABOLIC SYNDROME AND INSULIN RESISTANCE ARE ASSOCIATED WITH MAXIMUM HEPATITIS C LIPOVIRAL PARTICLES IN GENOTYPE 1 INFECTION

Background and Aims: HCV has a direct role in the pathogenesis of insulin resistance. Patients with chronic HCV and insulin resistance are less likely to respond to antiviral therapy and are at risk for more rapid fibrosis progression. Insulin resistance is most strongly associated with HCV genotype (G)1. Infectious HCV particles have a low density due to association with triglyceride rich lipoproteins (TRLs) as lipoviral particles (LVP). We have reported that LVP levels are dynamic and can increase to a maximum level postprandially by transfer onto TRLs including chylomicrons, VLDL and lipid emulsions both in vivo and ex vivo [1]. We aimed to evaluate the relationships between the maximum amount of LVP in vivo and clinical and metabolic parameters. Methods: 53 chronic HCV G1 patients provided fasting blood samples. The maximum LVP ratio (LVPr-max) was measured by incubating fasting plasma with a lipid emulsion prior to separation using a size filter. HCV RNA was quantitated from the filtrate and retentate and LVPr-max was calculated (retentate/retentate + filtrate). Results: The median LVPr-max was 0.28 but varied widely from 0.07 to 0.86. LVPr-max was significantly correlated with HOMAIR (r = 0.362, p = 0.008). LVPr-max was significantly increased in patients with co-existing metabolic syndrome (median LVPr-max 0.49, n = 11) compared to those without metabolic syndrome (median 0.23), p = 0.001. LVPr-max did not correlate with plasma apoE concentration. There was no association of LVPr-max with IL28B or PNPLA3 genotypes. Conclusions: This study provides some mechanistic insights into the interaction of HCV with metabolic syndrome and insulin resistance, suggesting an association with increased amounts of post-prandial infectious HCV particles.