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Insulin resistance and low-density apolipoprotein B-associated lipoviral particles in hepatitis C virus genotype 1 infection

Lookup NU author(s): Dr Simon Bridge, Dr David Sheridan, Dr Daniel Felmlee, Dr Soren Nielsen, Dr R Neely, Emeritus Professor Geoffrey Toms, Professor Margaret Bassendine

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Abstract

Background: The density of hepatitis C virus (HCV) in plasma is heterogeneous but the factors which influence this are poorly understood. Evidence from animal models and cell culture suggest that low-density apolipoprotein B (apoB)-associated HCV lipoviral particles (LVP) are more infectious than high-density HCV. Objective: To measure LVP in patients with chronic hepatitis C genotype 1 (CHC-G1) and examine metabolic determinants of LVP load. Patients 51 patients with CHC-G1 infection. Methods: Fasting lipid profiles and homeostasis model assessment of insulin resistance (HOMA-IR) were determined in 51 patients with CHC-G1. LVP and non-LVP viral load were measured by real-time PCR of plasma at density <1.07 g/ml and >1.07 g/ml, respectively, following iodixanol density gradient ultracentrifugation. The LVP ratio was calculated using the formula: LVP/(LVP + non-LVP). Results: The mean LVP ratio was 0.241 but varied 25-fold (from 0.029 to 0.74). Univariate analysis showed that the LVP ratio correlated with HOMA-IR (p=0.004) and the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio (p=0.004), but not with apoB. In multivariate analysis, HOMA-IR was the main determinant of LVP load (log10IU/ml) (R2=16.6%; p=0.037) but the TG/HDL-C ratio was the strongest predictor of the LVP ratio (R2=24.4%; p=0.019). Higher LVP ratios were associated with non-response to antiviral therapy (p=0.037) and with greater liver stiffness (p=0.001). Conclusion: IR and associated dyslipidaemia are the major determinants of low-density apoB-associated LVP in fasting plasma. This provides a possible mechanism to explain why IR is associated with more rapidly progressive liver disease and poorer treatment outcomes. Copyright Article author (or their employer) 2010.

Publication metadata

Author(s): Bridge SH, Sheridan DA, Felmlee DJ, Nielsen SU, Thomas HC, Taylor-Robinson SD, Neely RDG, Toms GL, Bassendine M

Publication type: Article

Publication status: Published

Journal: Gut

Year: 2010

Volume: 60

Issue: 5

Pages: 680-687

Print publication date: 12/10/2010

ISSN (print): 0017-5749

ISSN (electronic): 1468-3288

Publisher: BMJ Group

URL: http://dx.doi.org/10.1136/gut.2010.222133

DOI: 10.1136/gut.2010.222133

PubMed id: 20940286

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